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cartinamic Medicina basada en Evidencia en tratamiento lesiones focales de Cartílago. ‘Nanofracture Autologous Matrix-induced Chondrogenesis’

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Page 1: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

cartinamic cartinamic

Medicina basada en Evidencia en tratamiento lesiones focales de Cartílago.

‘Nanofracture Autologous Matrix-induced Chondrogenesis’

Pau Margarit

cartinamic cartinamic

Medicina basada en Evidencia en tratamiento lesiones focales de Cartílago.

‘Nanofracture Autologous Matrix-induced Chondrogenesis’

Pau Margarit

Page 2: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

cartinamic cartinamic

Medicina basada en Evidencia en tratamiento lesiones focales de Cartílago.

‘Nanofracture Autologous Matrix-induced Chondrogenesis’

Pau Margarit

‘Nanofracture Autologous Matrix-induced Chondrogenesis’

Behrens_Bentin_06_2015. The KneeNAMIC

Pleuri-potential cells

NANO FX

The membrane is pressed into the defect (Fig. 1d). It is importantthat the walls of the defect are smooth and clearly defined. The mem-brane should be slightly undersized and beneath the surface of theneighboring cartilage matrix as this will help the membrane to stay inplace. A blunt raspatorium may be helpful to apply full pressure onthe membrane and to fix it in the joint.

Once themembrane is fixed the joint is gentlymoved to see that thecollagen membrane remains in place. Irrigation of the joint is discour-aged as this may almost certainly result in membrane dislocation andremoval of the desired blood clot.

3. Postoperative management and rehabilitation

Recommendation for postoperative rehabilitation after subchondralsurgery is mixed, indicating that this issue is far from being resolved.Most studies evaluating microfracturing recommend partial weightbearing for up to sixweeks [2–4,10,11] or do not address this issue at all.

This partialweight bearingpertains to the possible risk of a compres-sion fracture after microfracturing due to small and ill-defined bonebridges between the V-shaped holes [6] which might not bear enoughweight. Articular remodeling and chondral maturation may take up tosix months so limited weight bearing for a certain amount of time isimportant. Studies show, however [7,8] that the remodeling of thechondral matrix may actually profit from early mobilization using acombination of compression and shear forces. Since there is sufficientbridging between the drilled holes and the holes are straight thereshould be no reason for a subchondral impression fracture (Fig. 1c).The authors recommend an orthosis with unlimited range of motion(ROM) for five days, after this period early mobilization of the joint byphysical therapy. Partial weight bearing should be for two weeks only.For rehabilitation, the authors recommend a skateboard like motiondevice. This is easily accessible by most patients and physiotherapistsand combines ideally compression and shear forces.

4. Discussion

The first mid-term studies on microfracturing and the AMIC©technique show encouraging results, advancing this technology fromexperimental towards clinically applicable [4,5,10,11]. These surgicaltechniques may also be performed arthroscopically [9]. The NAMIC©procedure may also be performed arthroscopically (Fig. 1b).

There are clear statements in the literature [12–14] that differentdrilling techniques and sizes of the drills may lead to improved cartilageregeneration. The deeper the drilling is performed the more MSCs areavailable for cartilage regeneration. Small subchondral drill holes of1.0 mm seem to stimulate a better cartilage regeneration in the sheepmodel [15].

There are theoretically several advantages of theNAMIC© technology:The patient has amuch shorter rehabilitation time allowing earlier returnto daily activity andwork. There seems to be a sufficient defect filling andremodeling of the cartilage surface without subchondral cysts or internalosteophytes (Fig. 2). The procedure is reproducible which is a major ad-vantage in designing and comparing studies. The AMIC technique re-quires microfracturing which may lead to subchondral impressionfractures. Since microfracturing is not a standardized procedure [6],there are many tools with differently shaped and sized tips available formicrofracturing, comparing studies is difficult. The correct size and lengthof subchondral drilling remain under discussion as is the extent ofsubchondral surgery [16]. The potential of autologous subchondralMSCs, however, seems to be increasingly undisputed [17].

Macroscopically and histologically, after nanofracturing andapplication of a collagen I/III membrane, fibrous cartilage forms in con-junction with the existing hyaline cartilage (Fig. 4a and b). After oneyear, the membrane seems to be almost completely dissolved with newgrowth of fibrous cartilage into and eventually replacing it (Fig. 4b).Nanofracturing alone reaches a similar histological result (Fig. 4a). After

one year, MRI scans and arthroscopy yield new cartilage formation(Figs. 2 and 3) and defect closure confirming the theoretical back-ground of subchondral surgery.

Cartilage cells do neither jump nor fall into the defect— they tend torest in theirmatrixwhich they obviously produce, and thematrix needsto be shaped as needed for the joint. This would also prevent the forma-tion of internal osteophytes as these are a sign of excessive matrix for-mation. The perfect motion of the knee joint would be the skateboard-typemovement as this includes weight bearing, shear and compression

Fig. 2.MRI one year after NAMIC medial femoral condyle. Note the regenerated cartilage(arrow).

Fig. 3. One year after NAMIC of a chondral defect of the medial femur condyle. Note thenew car cartilage tissue that filled the defect completely (arrow) but also the progressivedeterioration of the surrounding tissue due to generalized osteoarthritis.

3J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

forces. In nanofracturing, the drilled holes are always nine millimetersdeep and one millimeter wide, so the results should be reproducible.The risk for a subchondral fracture is low. As this proceduremay be per-formed all arthroscopically with the help of an awl the trauma for thepatient ismuch lower than in the traditional AMIC technique. It is desir-able to have reproducible methods for cartilage regeneration so studiesmay be designed, performed and compared in a betterway. There is alsoan increasing need to prove the efficiency of new operativemethods forreimbursement purposes for health insurance companies. This is bestdone by standardized methods where several independent studiesmay be compared.

There are some disadvantages: The development of differentawls for application in the knee, hip and shoulder joint is chal-lenging. The needle for nanofracturing should be flexible butmay not always be applied at the correct angle. Sometimes a needletends to bend to the side instead of penetration the subchondral bone.Care should be taken to fix the nanofracturing awl at the correct angleas there is considerable risk that the wire may slip and perforate sur-rounding cartilage.

We still do not know if a nine millimeters deep penetration of thesubchondral room is sufficient. At this time, the nine millimeters limit isset by the Nitinol material of the needle. The stability of the needle alsoneeds to be ascertained as needle breaking would lead to unnecessarytrauma for the patient. The advantage of 1.0 mm wire diameter isconfirmed by animal studies [15].

5. Conclusion

The NAMIC© procedure further develops the collagen membraneinduced chondrogenesis procedures (AMIC©). Small holes in combina-tion with subchondral needling and a stable, reliable membrane couldprovide a method to achieve reproducible results and a standardizedprocedure. The latest theoretical results in cartilage regeneration inthe literature seem to confirm this further development. The postoper-ative rehabilitation is shortened by 2/3 as compared to the traditionalAMIC© procedure. First results are encouraging and compared well tothe AMIC© procedure. Further studies, however, are needed, especiallyin a proposed shortened rehabilitation protocol. As in all regenerativecartilage methods, general osteoarthritis of a joint may not be stoppedand one problem that has been solvedmay just be followed by another.After two years of application, the authors observe that there seems tobe a worse outcome after NAMIC© in patients with osteoarthritis ascompared to patients with post-traumatic defects.

The authors are currently planning a study concerning the follow-upof their NAMIC© patients. From preliminary encouraging observationswe postulate that the NAMIC©-procedure will compare well to theAMIC© procedure with the advantages of a much shorter rehab timeand a comparability to other methods.

Acknowledgments

The authors would like to sincerely thank the patients treated withNAMIC© from Davos, Switzerland, for their kind permission to havetheir data published.

References

[1] Makris EA, Gomoll AH, Malizos KN, Athanasiou KA. Repair and tissue engineeringtechniques for articular cartilage. Nat Rev Rheumatol 2014. http://dx.doi.org/10.1038/nrrheum.2014.157 (Epub ahead of print).

[2] Benthien JP, Behrens P. The treatment of chondral and osteochondral defects of theknee with autologous matrix-induced chondrogenesis (AMIC): method descriptionand recent developments. Knee Surg Sports Traumatol 2011;19:1316–9. http://dx.doi.org/10.1007/s00167-010-1356-1.

[3] Steadman JR, Rodkey WG, Rodrigo JJ. “Microfracture”: surgical technique and reha-bilitation to treat chondral defects. Clin Orthop Relat Res 2001;391:S362–9.

[4] Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-term results ofautologous matrix induced chondrogenesis (AMIC). Knee Surg Sports TraumatolArthrosc 2010;18:1456–64.

[5] Lee YHDL, Suzer F, Thermann H. Autologous matrix induced chondrogenesis in theknee: a review. Cartilage 2014;5(3):145–53.

[6] Benthien JP, Behrens P. Reviewing subchondral cartilage surgery: considerations forstandardized and outcome predictable cartilage remodellling. Int Orthop 2013;37:2139–45.

[7] Wang N, Grad S, Stoddart MJ, Niemeyer P, Reising K, Schmal H, et al. Particulate car-tilage under bioreactor induced compression-shear. Int Orthop 2014;38(5):1105–11.

[8] Schaetti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, et al. A combination ofshear and dynamic compression leads to mechanically induced chondrogenesis ofhuman mesenchymal stem cells. Eur Cell Mater 2011;22:214–25.

[9] Piontek T, Ciemniewska-Gorzela K, Szulc A, Naczk J, Slomczykowski M. All-arthroscopic AMIC procedure for repair of cartilage defects. Knee Surg SportsTraumatol Arthrosc 2012;20:922–5.

[10] Asik M, Ciftci F, Sen C, Erdil M, Atalar A. The microfracture technique for the treat-ment of full-thickness articular lesions of the knee: midterm results. Arthroscopy2008;24(11):1214–20. http://dx.doi.org/10.1016/j.arthro.2008.06.015.

[11] Mithoefer K, McAdam T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy ofthe microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 2009;37:2053–63. http://dx.doi.org/10.1177/0363546508328414.

[12] Chen H, Hoemann CD, Sun J, Chevrier A, McKee MD, Shive MS, et al. Depth ofsubchondral perforation influences the outcome of bone marrow stimulation cartilagerepair. J Orthop Res 2011;29(8):1178–84. http://dx.doi.org/10.1002/jor.21386.

a

b

Fig. 4. a. Histology of newly formed fibrous cartilage at the border of hyaline/fibrouscartilage (white arrow) nine months after nanofracturing alone. The black arrow marksthe joint surface. b. Histological picture 12months afterNAMIC©: There seems to be a con-tinuous border of hyaline and fibrous cartilage (white arrow). Fragments of the collagenmembrane may be seen with fibrous cartilage growing into it (black arrow).Photowith kind permission ofDr.M.Germer, Department of Pathology, CantonalHospital,Chur, Switzerland. Photo with kind permission of the Department of Pathology, CantonalHospital, Chur, Switzerland.

4 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

Cartimaix – una membrana con dos caras

Cartimaix tiene dos caras: una cara densa y suave y una cara fibrosa abierta y rugosa. El producto combina una función de barrera para proteger el área de regeneración con una base adherente para los condrocitos o las células madre que migran de la médula ósea.

La membrana se implanta con la cara densa y suave mirando hacia el espacio articular. La membrana cubre como un escudo protector el área de tratamiento. Las células y los factores de promoción del crecimiento se mantienen allí donde son necesarios para una regeneración óptima del tejido cartilaginoso.

La cara rugosa se implanta mirando hacia el defecto del cartílago y con su estructura fibrosa abierta sirve como una matriz ideal para la adherencia de las células de regeneración del cartílago.

La cara suave de Cartimaix

Las dos caras de Cartimaix en sección transversal

La cara rugosa de Cartimaix

Características destacadas de Cartimaix

• Material altamente purificado y seguro basado en colágeno porcino y elastina • Manejo y estabilidad mecánica excelente tanto de la membrana seca como de

la membrana rehidratada • Creación de un entorno protegido para la regeneración del cartílago donde se

mantienen las células regeneradoras del cartílago y las sustancias que favorecen la formación del cartílago. Por tanto, no hay pérdida de células ni de sustancias valiosas al espacio articular

• Compatibilidad celular científicamente probada con las células regeneradoras del cartílago

• Comparado con geles, resorción más lenta y mayor resistencia abrasiva a las fuerzas tangenciales

• Remodelación completa del colágeno natural no reticulado durante la regeneración del cartílago sin la liberación de sustancias tóxicas o modificadoras del pH

cartinamic cartinamic

Matricel GmbH | Kaiserstrasse 100, 52134 Herzogenrath, Germany

Tel.: +49 2407 5644-0 | Fax: +49 2407 5644-10 | E-Mail: [email protected]

www.matricel.com | www.cartimaix.comRev

. 091

5

Matricel is a manufacturer of medical devices and starting

materials for pharmaceuticals, which are certified e.g. in

Europe, Canada and the United States and are used as

degradable implants in the field of Regenerative Medicine.

The clinical application spectrum of Matricel products ranges

from orthopedics and trauma surgery to plastic surgery,

dermatology and the dental field.

About Matricel

Cleanroom production at Matricel

Cartimaix is available in the following product sizes and is supplied in double

sterile packaging. Each product contains a Cartimaix membrane and a sterile

aluminium Template in the size 40 mm x 50 mm.

CAR4050

Order information

Ordering and further information on Cartimaix and literature references are available on the internet at www.cartimaix.com or www.matricel.com and by phone +49 (0)2407 - 56 44 20.

Order-No.

Product size

Packaging unit

CAR2530

CAR2530

25 mm x 30 mm

1 Cartimaix Membrane + 1 Template

CAR3040

CAR3040

30 mm x 40 mm

1 Cartimaix Membrane + 1 Template

CAR4050

40 mm x 50 mm

1 Cartimaix Membrane + 1 Template

Aluminium Template

El fabricante, Matricel Matricel es un fabricante de dispositivos médicos y materiales de base para farmacéuticas que están certificados por ej. en Europa, Canadá y Estados Unidos y se usan como implantes degradables en el campo de la medicina regenerativa. El espectro de aplicación clínica de los productos Matricel va desde la cirugía ortopédica y la traumatología hasta la cirugía plástica, la dermatología y el sector dental.

Otra información de interés

Cartimaix está disponible en las siguientes medidas y se suministra en doble embalaje estéril . Cada producto contiene una membrana Cartimaix y una plantilla de aluminio estéril de 40x50 mm

Cartimaix – una membrana con dos caras

Cartimaix tiene dos caras: una cara densa y suave y una cara fibrosa abierta y rugosa. El producto combina una función de barrera para proteger el área de regeneración con una base adherente para los condrocitos o las células madre que migran de la médula ósea.

La membrana se implanta con la cara densa y suave mirando hacia el espacio articular. La membrana cubre como un escudo protector el área de tratamiento. Las células y los factores de promoción del crecimiento se mantienen allí donde son necesarios para una regeneración óptima del tejido cartilaginoso.

La cara rugosa se implanta mirando hacia el defecto del cartílago y con su estructura fibrosa abierta sirve como una matriz ideal para la adherencia de las células de regeneración del cartílago.

La cara suave de Cartimaix

Las dos caras de Cartimaix en sección transversal

La cara rugosa de Cartimaix

Características destacadas de Cartimaix

• Material altamente purificado y seguro basado en colágeno porcino y elastina • Manejo y estabilidad mecánica excelente tanto de la membrana seca como de

la membrana rehidratada • Creación de un entorno protegido para la regeneración del cartílago donde se

mantienen las células regeneradoras del cartílago y las sustancias que favorecen la formación del cartílago. Por tanto, no hay pérdida de células ni de sustancias valiosas al espacio articular

• Compatibilidad celular científicamente probada con las células regeneradoras del cartílago

• Comparado con geles, resorción más lenta y mayor resistencia abrasiva a las fuerzas tangenciales

• Remodelación completa del colágeno natural no reticulado durante la regeneración del cartílago sin la liberación de sustancias tóxicas o modificadoras del pH

Propuesta basada en la Evidencia

Características de la membrana:

Administration (FDA) and Communauté Européenne (CE)-approvedapplications.

2. Operative technique

It is recommended that patients receive magnetic resonanceimaging (MRI) scans and standing anteroposterior (a.p.) and lateral ra-diographs of their knee joints. The patella should be X rayed axially, anda 20 degrees flexion projection (Rosenberg profile) should be per-formed to evaluate the main weight bearing zone. An orthoradiogramis helpful if there are clinical hints for a mal-alignment of the leg axis.This should be discussed with the patient as varus or valgus deformitymay impede cartilage regeneration. A correction of the axis in combina-tion with subchondral surgery may be advisable.

Indications for NAMIC© are basically the same as the authors'recommendation for nanofracturing [6]: A symptomatic InternationalCartilage Repair Society (ICRS) grade 4 cartilage lesion, the lesion shouldnot be bigger than four square centimeters and should lie in the weightbearing region of the joint. Kissing lesions should also be excluded as inthe AMIC© procedure. The age limit is not yet determined. The authorsprefer not to set a limit at this time as there is not enough data tosupport any limit.

Surgery on the knee is performedwith the patient supine in an ordi-nary arthroscopy setup. The first step is a diagnostic arthroscopy whichshould verify the pre-operatively suspected lesions. There should be athorough check of the cruciate ligaments as stability of the anteriorcruciate ligament is paramount for joint stability and for the healing ofthe treated cartilage defect.

Possible accompanying lesions of the menisci may be addressed(suture if possible or partial resection if suturing is no longer an option)at the time of arthroscopy.

The cartilage defect is measured with the hook in order to deter-mine the size of the implant. The membrane is a collagen I/III mem-brane of the next generation (Cartimaix, Matricell, Herzogenrath,Germany) which allows much stability and is partially resistant toagglomeration in a wet environment. There are two sides of themembrane. The rough side faces the subchondral bone; the smoothside faces the joint.

With the help of a curette, the defect is debrided and the subchondrallayer is identified.

Nanofracturing is performed, keeping in mind that each hole has adefined length of nine millimeters and a diameter of one millimeter(Fig. 1a and c).

Fibrin glue for the attachment of the membrane may be appliedthrough the nanofracturing awl (Arthrosurface, Franklin, MA, USA)with a special adaptor (Fig. 1b and d). The membrane should be cutprior to the application of the fibrin glue. In an arthroscopically assistedmini-open technique, an aluminum templatemay be used to determinethe size of the defect. The application of fibrin glue and the attachmentof the membrane is best done in a dry environment. This may be eitherperformed arthroscopically or in an arthroscopically assistedmini-opentechnique (Fig. 1b).

In an all-arthroscopic setting (Fig. 1b), the tip of the hook helpsto determine the membrane size. In any case should the smooth sur-face be marked with a sterile pen so recognition inside the joint isfacilitated.

1

a b

c d

Fig. 1. a: Needling of a subchondral defect with the nanofracturing needle applied through a nanofracturing awl. b: Application of fibrin glue through the nanofracturing awl in an all-arthroscopic NAMIC© procedure. Note the collagen membrane (marked blue) in the background (arrow). c: Subchondral one millimeter drill holes penetrating nine millimeters deepafter nanofracturing. Note the gaps between the holes permitting sufficient bridging to prevent subchondral fracture. d: The defect is covered with the collagen I/III membrane whichis fixed with fibrin glue. The purple grid marks the external side of the membrane. The membrane is placed slightly below the level of the adjoining cartilage to prevent its accidentalremoval in motion. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

2 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

+

II

CARTIMAIX

Menos Invasivo & Más Migración Celular

Tecnología probada > 12 años Número 1 en Alemania

Permite tratamiento lesiones condrales puras y

Osteocondrales con aporte óseo

Page 3: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic CartiNamic es un kit para reparación de lesiones focales de cartílago que consta de

una matriz de colágeno I/III estructurada , acelular y biodegradable, indicada para cubrir defectos de cartílago, y un instrumento de precisión para la preparación de la lesión mediante estimulación mínimamente invasiva de la médula ósea subcondral, según la técnica publicada NAMIC. Behrens et al. 2015 The Knee

cartinamic cartinamic Propuesta basada en la Evidencia

Nanofractured autologous matrixinduced chondrogenesis(NAMIC©) — Further development of collagen membrane aidedchondrogenesis combined with subchondral needlingA technical note

Jan P. Benthien a,⁎, Peter Behrens b

a Department of Orthopaedic and Trauma Surgery, Davos Hospital, Davos, Switzerlandb CUNO Orthopaedic Surgery, Hamburg, Germany

a b s t r a c ta r t i c l e i n f o

Article history:Received 21 January 2015Received in revised form 22 April 2015Accepted 22 June 2015Available online xxxx

Keywords:NanofracturingAMIC©Cartilage defectSmall holesSubchondral needling

Purpose: This technical note introduces a further development of the autologousmatrix induced chondrogenesis(AMIC©) technology for regenerative surgery of cartilage defects considering latest data in the literature. Thepotential of subchondral mesenchymal stem cell stimulation for cartilage repair is combined with a membranetechnique to enhance efficiency of cartilage regeneration. The nanofractured autologousmatrixinduced chondro-genesis (NAMIC©) procedure is suitable for the knee, hip, ankle, shoulder and elbow joints.Methods: A standardized subchondral needling procedure (nanofracturing) is combined with fixation of acollagen I/III membrane to regenerate cartilage defects. Its advantages over microfracturing are smaller holes,deeper perforation into the subchondral space, a standardized procedure and earlier rehabilitation of the patient.The collagen membrane protects the blood clot forming after nanofracturing. The NAMIC© procedure may beperformed arthroscopically alone, or in a combined arthroscopic setting with a mini-arthrotomy.Results: This is a further development of the AMIC© technologywhich allows earlier rehabilitation of the patient.The procedure is standardized. Early clinical results are encouraging. Nevertheless, caution is advised in the eval-uation of this method as in that of any cartilage regenerating method.Conclusion: The development of standardized subchondral regenerative procedures is important as only reliableclinical studies will give non-biased results. The NAMIC© procedure and the nanofracturing associated with itcould be a promising step. As the rehabilitation period may be significantly shortened there is an earlier re-integration of the patient into the working life as compared to the AMIC© procedure.Level of Evidence: 4.

© 2015 Elsevier B.V. All rights reserved.

1. Introduction

Chondral and osteochondral defects may eventually lead to osteoar-thritis. It is important for a proper function of any joint that congruencyis re-established. Many methods for cartilage regeneration have beendescribed but there seems to be a trend for subchondral surgery usingthe autologous regenerative potential to have the greatest effects [1].There also seems to be a shift of paradigm in modern orthopaedics: In-stead of simply replacing damaged parts autologous joint regenerationseems to be favored.

The autologous matrixinduced chondrogenesis (AMIC©) as intro-duced by Behrens and Benthien [2] is an established method for carti-lage regeneration. It combines the widely applied microfracturingmethod as first introduced by Steadman et al. [3] with a collagen I/III

membrane. First results are encouraging [4,5]. There are several mem-brane induced chondrogenetic procedures with different scaffolds [1].Most of these use subchondral mesenchymal stem cells (MSCs) for car-tilage regeneration and the microfracturing technique.

However, six weeks partial weight bearing and disadvantages ofmicrofracturing, the risk of iatrogenic fractures and an unpredictable out-come due to amissing standardization of themethod has led the authorsto further develop subchondral surgery [6]. Small holes of a defineddiam-eter of onemillimeter and a penetration depth of ninemillimetersmaybeplaced as subchondral needling or nanofracturing. The postoperativerehab program was adapted to new finds in cartilage developmentin vitro [7,8]. Cartilage matrix seems to regenerate better and earlierwhen compression and shear pressure are applied. Percussion compres-sion should not be applied as this may disrupt the matrix formation.

Photographies and histologies in this paper are of clinical set-upsandwastematerial for which the patients explicitly consented for anony-mous publication. Nanofracturing and its tools are Food and Drug

The Knee xxx (2015) xxx–xxx

⁎ Corresponding author.E-mail address: [email protected] (J.P. Benthien).

THEKNE-02105; No of Pages 5

http://dx.doi.org/10.1016/j.knee.2015.06.0100968-0160/© 2015 Elsevier B.V. All rights reserved.

Contents lists available at ScienceDirect

The Knee

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

‘Condrogésis Autóloga inducida por técnica mínimamente invasiva de estimulación de la médula ósea subcondral (Nanofractura) asistida por matriz de colágeno biodegradable estructurada’

‘Nanofracture Autologous Matrix-induced Chondrogenesis’

Literature1. Biant, L. C., Bentley, G., Vijayan, S., Skinner, J. A. & Carrington,

R. W. J. Long-term Results of Autologous Chondrocyte Implantation

in the Knee for Chronic Chondral and Osteochondral Defects. Am. J.

Sports Med. 42, 2178–83 (2014).

2. Knutsen, G. et al. Autologous chondrocyte implantation compa-

red with microfracture in the knee. A randomized trial. J. Bone Joint

Surg. Am. 86-A, 455–64 (2004).

3. Jäger, M., Feser, T., Denck, H. & Krauspe, R. Proliferation and os-

teogenic differentiation of mesenchymal stem cells cultured onto three

different polymers in vitro. Ann. Biomed. Eng. 33, 1319–32 (2005).

4. Gooding, C. R. et al. A prospective, randomised study comparing

two techniques of autologous chondrocyte implantation for osteo-

chondral defects in the knee: Periosteum covered versus type I/III col-

lagen covered. Knee 13, 203–10 (2006).

5. Chen, J. M., Willers, C., Xu, J., Wang, A. & Zheng, M.-H. Autolo-

gous tenocyte therapy using porcine-derived bioscaffolds for massive

rotator cuff defect in rabbits. Tissue Eng. 13, 1479–91 (2007).

6. Jäger, M. et al. Bone healing and migration of cord blood-derived

stem cells into a critical size femoral defect after xenotransplantation.

J. Bone Miner. Res. 22, 1224–33 (2007).

7. Iwasa, J., Engebretsen, L., Shima, Y. & Ochi, M. Clinical appli-

cation of scaffolds for cartilage tissue engineering. Knee Surg. Sports

Traumatol. Arthrosc. 17, 561–77 (2008).

8. Gomoll, A. H., Probst, C., Farr, J., Cole, B. J. & Minas, T. Use of

a type I/III bilayer collagen membrane decreases reoperation rates for

symptomatic hypertrophy after autologous chondrocyte implantation.

Am. J. Sports Med. 37 Suppl 1, 20S–23S (2009).

9. Brittberg, M. Cell carriers as the next generation of cell therapy for

cartilage repair: a review of the matrix-induced autologous chondrocy-

te implantation procedure. Am. J. Sports Med. 38, 1259–71 (2010).

10. Harris, J. D. et al. Failures, re-operations, and complications after

autologous chondrocyte implantation--a systematic review. Osteoarth-

ritis Cartilage 19, 779–91 (2011).

11. Saris, D. et al. Matrix-Applied Characterized Autologous Cultured

Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospec-

tive Randomized Trial. Am. J. Sports Med. 42, 1384–1394 (2014).

12. Brittberg, M., Price, A., Yu, Q., Kili, S. & Saris, D. Poster: SUMMIT

Trial : Matrix-induced Autologous Chondrocyte Implant versus Microf-

racture at 3 Years. in Poster AAOS Annu. Meet. 2015, Las Vegas,

Nevada (2015).

13. Dhollander, A. A. M. et al. Autologous matrix-induced chondroge-

nesis combined with platelet-rich plasma gel: technical description and

a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19,

536–42 (2010).

14. Gille, J. et al. Cell-Laden and Cell-Free Matrix-Induced Chondro-

genesis versus Microfracture for the Treatment of Articular Cartilage

Defects: A Histological and Biomechanical Study in Sheep. Cartilage 1,

29–42 (2010).

15. Gille, J. et al. Mid-term results of Autologous Matrix-Induced

Chondrogenesis for treatment of focal cartilage defects in the knee.

Knee Surg. Sports Traumatol. Arthrosc. 18, 1456–64 (2010).

16. Anders, S., Volz, M., Frick, H. & Gellissen, J. A Randomized, Con-

trolled Trial Comparing Autologous Matrix-Induced Chondrogenesis

(AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of

2 Centers. Open Orthop. J. 7, 133–43 (2013).

17. Gille, J. et al. Outcome of Autologous Matrix Induced Chondroge-

nesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch.

Orthop. Trauma Surg. 133, 87–93 (2013).

18. Bark, S. et al. Enhanced microfracture techniques in cartilage

knee surgery: Fact or fiction? World J. Orthop. 5, 444–9 (2014).

19. Lee, Y. H. D., Suzer, F. & Thermann, H. Autologous Matrix-In-

duced Chondrogenesis in the Knee: A Review. Cartilage 5, 145–153

(2014).

20. Benthien, J. P. & Behrens, P. Nanofractured autologous matrixin-

duced chondrogenesis (NAMIC©) — Further development of collagen

membrane aided chondrogenesis combined with subchondral need-

ling. Knee (2015). doi:10.1016/j.knee.2015.06.010

21. Benthien, J. P. & Behrens, P. Reviewing subchondral cartilage

surgery: considerations for standardised and outcome predictable car-

tilage remodelling: a technical note. Int. Orthop. 37, 2139–45 (2013).

22. Behrens, P., Varoga, D., Niemeyer, P. & Salzmann, G. Intraopera-

tive biologische Augmentation am Knorpel. Arthroskopie 26, 114–122

(2013).

23. Min, B.-H. et al. Effect of different bone marrow stimulation

techniques (BSTs) on MSCs mobilization. J. Orthop. Res. Off. Publ.

Orthop. Res. Soc. 31, 1814–1819 (2013).

24. Eldracher, M., Orth, P., Cucchiarini, M., Pape, D. & Madry, H.

Small Subchondral Drill Holes Improve Marrow Stimulation of Articular

Cartilage Defects. Am. J. Sports Med. 42, 2741–2750 (2014).

25. Benthien, J. P. & Behrens, P. The treatment of chondral and

osteochondral defects of the knee with autologous matrix-induced

chondrogenesis (AMIC): method description and recent developments.

Knee Surg. Sports Traumatol. Arthrosc. 19, 1316–9 (2011).

26. Piontek, T., Ciemniewska-Gorzela, K., Szulc, A., Naczk, J. &

Słomczykowski, M. All-arthroscopic AMIC procedure for repair of car-

tilage defects of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20,

922–5 (2012).

27. Hunziker, E. B. & Stähli, A. Surgical suturing of articular cartilage

induces osteoarthritis-like changes. Osteoarthritis Cartilage 16, 1067–

73 (2008).

cartinamic cartinamic Propuesta basada en la Evidencia

Nanofractured autologous matrixinduced chondrogenesis(NAMIC©) — Further development of collagen membrane aidedchondrogenesis combined with subchondral needlingA technical note

Jan P. Benthien a,⁎, Peter Behrens b

a Department of Orthopaedic and Trauma Surgery, Davos Hospital, Davos, Switzerlandb CUNO Orthopaedic Surgery, Hamburg, Germany

a b s t r a c ta r t i c l e i n f o

Article history:Received 21 January 2015Received in revised form 22 April 2015Accepted 22 June 2015Available online xxxx

Keywords:NanofracturingAMIC©Cartilage defectSmall holesSubchondral needling

Purpose: This technical note introduces a further development of the autologousmatrix induced chondrogenesis(AMIC©) technology for regenerative surgery of cartilage defects considering latest data in the literature. Thepotential of subchondral mesenchymal stem cell stimulation for cartilage repair is combined with a membranetechnique to enhance efficiency of cartilage regeneration. The nanofractured autologousmatrixinduced chondro-genesis (NAMIC©) procedure is suitable for the knee, hip, ankle, shoulder and elbow joints.Methods: A standardized subchondral needling procedure (nanofracturing) is combined with fixation of acollagen I/III membrane to regenerate cartilage defects. Its advantages over microfracturing are smaller holes,deeper perforation into the subchondral space, a standardized procedure and earlier rehabilitation of the patient.The collagen membrane protects the blood clot forming after nanofracturing. The NAMIC© procedure may beperformed arthroscopically alone, or in a combined arthroscopic setting with a mini-arthrotomy.Results: This is a further development of the AMIC© technologywhich allows earlier rehabilitation of the patient.The procedure is standardized. Early clinical results are encouraging. Nevertheless, caution is advised in the eval-uation of this method as in that of any cartilage regenerating method.Conclusion: The development of standardized subchondral regenerative procedures is important as only reliableclinical studies will give non-biased results. The NAMIC© procedure and the nanofracturing associated with itcould be a promising step. As the rehabilitation period may be significantly shortened there is an earlier re-integration of the patient into the working life as compared to the AMIC© procedure.Level of Evidence: 4.

© 2015 Elsevier B.V. All rights reserved.

1. Introduction

Chondral and osteochondral defects may eventually lead to osteoar-thritis. It is important for a proper function of any joint that congruencyis re-established. Many methods for cartilage regeneration have beendescribed but there seems to be a trend for subchondral surgery usingthe autologous regenerative potential to have the greatest effects [1].There also seems to be a shift of paradigm in modern orthopaedics: In-stead of simply replacing damaged parts autologous joint regenerationseems to be favored.

The autologous matrixinduced chondrogenesis (AMIC©) as intro-duced by Behrens and Benthien [2] is an established method for carti-lage regeneration. It combines the widely applied microfracturingmethod as first introduced by Steadman et al. [3] with a collagen I/III

membrane. First results are encouraging [4,5]. There are several mem-brane induced chondrogenetic procedures with different scaffolds [1].Most of these use subchondral mesenchymal stem cells (MSCs) for car-tilage regeneration and the microfracturing technique.

However, six weeks partial weight bearing and disadvantages ofmicrofracturing, the risk of iatrogenic fractures and an unpredictable out-come due to amissing standardization of themethod has led the authorsto further develop subchondral surgery [6]. Small holes of a defineddiam-eter of onemillimeter and a penetration depth of ninemillimetersmaybeplaced as subchondral needling or nanofracturing. The postoperativerehab program was adapted to new finds in cartilage developmentin vitro [7,8]. Cartilage matrix seems to regenerate better and earlierwhen compression and shear pressure are applied. Percussion compres-sion should not be applied as this may disrupt the matrix formation.

Photographies and histologies in this paper are of clinical set-upsandwastematerial for which the patients explicitly consented for anony-mous publication. Nanofracturing and its tools are Food and Drug

The Knee xxx (2015) xxx–xxx

⁎ Corresponding author.E-mail address: [email protected] (J.P. Benthien).

THEKNE-02105; No of Pages 5

http://dx.doi.org/10.1016/j.knee.2015.06.0100968-0160/© 2015 Elsevier B.V. All rights reserved.

Contents lists available at ScienceDirect

The Knee

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

‘Condrogésis Autóloga inducida por técnica mínimamente invasiva de estimulación de la médula ósea subcondral (Nanofractura) asistida por matriz de colágeno biodegradable estructurada’

‘Nanofracture Autologous Matrix-induced Chondrogenesis’

Literature1. Biant, L. C., Bentley, G., Vijayan, S., Skinner, J. A. & Carrington,

R. W. J. Long-term Results of Autologous Chondrocyte Implantation

in the Knee for Chronic Chondral and Osteochondral Defects. Am. J.

Sports Med. 42, 2178–83 (2014).

2. Knutsen, G. et al. Autologous chondrocyte implantation compa-

red with microfracture in the knee. A randomized trial. J. Bone Joint

Surg. Am. 86-A, 455–64 (2004).

3. Jäger, M., Feser, T., Denck, H. & Krauspe, R. Proliferation and os-

teogenic differentiation of mesenchymal stem cells cultured onto three

different polymers in vitro. Ann. Biomed. Eng. 33, 1319–32 (2005).

4. Gooding, C. R. et al. A prospective, randomised study comparing

two techniques of autologous chondrocyte implantation for osteo-

chondral defects in the knee: Periosteum covered versus type I/III col-

lagen covered. Knee 13, 203–10 (2006).

5. Chen, J. M., Willers, C., Xu, J., Wang, A. & Zheng, M.-H. Autolo-

gous tenocyte therapy using porcine-derived bioscaffolds for massive

rotator cuff defect in rabbits. Tissue Eng. 13, 1479–91 (2007).

6. Jäger, M. et al. Bone healing and migration of cord blood-derived

stem cells into a critical size femoral defect after xenotransplantation.

J. Bone Miner. Res. 22, 1224–33 (2007).

7. Iwasa, J., Engebretsen, L., Shima, Y. & Ochi, M. Clinical appli-

cation of scaffolds for cartilage tissue engineering. Knee Surg. Sports

Traumatol. Arthrosc. 17, 561–77 (2008).

8. Gomoll, A. H., Probst, C., Farr, J., Cole, B. J. & Minas, T. Use of

a type I/III bilayer collagen membrane decreases reoperation rates for

symptomatic hypertrophy after autologous chondrocyte implantation.

Am. J. Sports Med. 37 Suppl 1, 20S–23S (2009).

9. Brittberg, M. Cell carriers as the next generation of cell therapy for

cartilage repair: a review of the matrix-induced autologous chondrocy-

te implantation procedure. Am. J. Sports Med. 38, 1259–71 (2010).

10. Harris, J. D. et al. Failures, re-operations, and complications after

autologous chondrocyte implantation--a systematic review. Osteoarth-

ritis Cartilage 19, 779–91 (2011).

11. Saris, D. et al. Matrix-Applied Characterized Autologous Cultured

Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospec-

tive Randomized Trial. Am. J. Sports Med. 42, 1384–1394 (2014).

12. Brittberg, M., Price, A., Yu, Q., Kili, S. & Saris, D. Poster: SUMMIT

Trial : Matrix-induced Autologous Chondrocyte Implant versus Microf-

racture at 3 Years. in Poster AAOS Annu. Meet. 2015, Las Vegas,

Nevada (2015).

13. Dhollander, A. A. M. et al. Autologous matrix-induced chondroge-

nesis combined with platelet-rich plasma gel: technical description and

a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19,

536–42 (2010).

14. Gille, J. et al. Cell-Laden and Cell-Free Matrix-Induced Chondro-

genesis versus Microfracture for the Treatment of Articular Cartilage

Defects: A Histological and Biomechanical Study in Sheep. Cartilage 1,

29–42 (2010).

15. Gille, J. et al. Mid-term results of Autologous Matrix-Induced

Chondrogenesis for treatment of focal cartilage defects in the knee.

Knee Surg. Sports Traumatol. Arthrosc. 18, 1456–64 (2010).

16. Anders, S., Volz, M., Frick, H. & Gellissen, J. A Randomized, Con-

trolled Trial Comparing Autologous Matrix-Induced Chondrogenesis

(AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of

2 Centers. Open Orthop. J. 7, 133–43 (2013).

17. Gille, J. et al. Outcome of Autologous Matrix Induced Chondroge-

nesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch.

Orthop. Trauma Surg. 133, 87–93 (2013).

18. Bark, S. et al. Enhanced microfracture techniques in cartilage

knee surgery: Fact or fiction? World J. Orthop. 5, 444–9 (2014).

19. Lee, Y. H. D., Suzer, F. & Thermann, H. Autologous Matrix-In-

duced Chondrogenesis in the Knee: A Review. Cartilage 5, 145–153

(2014).

20. Benthien, J. P. & Behrens, P. Nanofractured autologous matrixin-

duced chondrogenesis (NAMIC©) — Further development of collagen

membrane aided chondrogenesis combined with subchondral need-

ling. Knee (2015). doi:10.1016/j.knee.2015.06.010

21. Benthien, J. P. & Behrens, P. Reviewing subchondral cartilage

surgery: considerations for standardised and outcome predictable car-

tilage remodelling: a technical note. Int. Orthop. 37, 2139–45 (2013).

22. Behrens, P., Varoga, D., Niemeyer, P. & Salzmann, G. Intraopera-

tive biologische Augmentation am Knorpel. Arthroskopie 26, 114–122

(2013).

23. Min, B.-H. et al. Effect of different bone marrow stimulation

techniques (BSTs) on MSCs mobilization. J. Orthop. Res. Off. Publ.

Orthop. Res. Soc. 31, 1814–1819 (2013).

24. Eldracher, M., Orth, P., Cucchiarini, M., Pape, D. & Madry, H.

Small Subchondral Drill Holes Improve Marrow Stimulation of Articular

Cartilage Defects. Am. J. Sports Med. 42, 2741–2750 (2014).

25. Benthien, J. P. & Behrens, P. The treatment of chondral and

osteochondral defects of the knee with autologous matrix-induced

chondrogenesis (AMIC): method description and recent developments.

Knee Surg. Sports Traumatol. Arthrosc. 19, 1316–9 (2011).

26. Piontek, T., Ciemniewska-Gorzela, K., Szulc, A., Naczk, J. &

Słomczykowski, M. All-arthroscopic AMIC procedure for repair of car-

tilage defects of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20,

922–5 (2012).

27. Hunziker, E. B. & Stähli, A. Surgical suturing of articular cartilage

induces osteoarthritis-like changes. Osteoarthritis Cartilage 16, 1067–

73 (2008).

Indicación

Descripción

Page 4: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

cartinamic cartinamic Propuesta de Algoritmo de tratamiento

Defect size 0 – 2 cm2 2 – 4 cm2 4 – 12 cm2 > 12 cm2

Grade 2

Grade 1

Lavage / Debridement / Cartilage smoothening

No operative treatment

Grade 3 / Grade 4

MFX

CACI

MA-MFX / NAMIC®

MFX

Treatment methods for cartilage regeneration

The choice of current treatment methods for the therapy of traumatic and degenerative cartilage defects is based on a scheme dependent on the size of the defect and the ICRS classification (Grade 1-4).

IN GRADE 3-4 DEFECTS AND WITH INCREASING DEFECT SIZE, MORE COMPLEX REGENERATION METHODS ARE REQUIRED:

Healthy Cartilage Grade 4 DefectGrade 1 / Grade 2 Defect Grade 3 Defect

lesion of more than 50% of the cartilage thickness

complete lesion of the cartilage, extending into

subchondral bone

light fissures of the cartilage tissue

• For defect sizes up to 2 cm², usually no matrix is used. The

typical treatment relies on a perforation of the subchondral

bone, e.g. Microfracturing (MFX) or Nanofracturing.

• For defect sizes between 2 and 12 cm² Cartimaix is used

for Matrix-Assisted Bone Marrow Stimulation (MA-MFX) or

advanced developments of this, for example NAMIC®.

• For very large defects Cartimaix is used in Collagen-covered

Autologous Chondrocyte Implantation (CACI) procedures.

Métodos de tratamiento para la regeneración del cartílago

La elección de los métodos de tratamiento actuales para el tratamiento de los defectos cartilaginosos traumáticos y degenerativos se basa en un esquema que depende del tamaño del defecto y la clasificación ICRS (grados 1-4).

Cartílago sanoDefecto de grado 1/grado 2 Fisuras leves del tejido cartilaginoso

Defecto de grado 3 Lesión de más del 50% del grosor del cartílago

Defecto de grado 4 Lesión completa del cartílago con extensión al hueso subcondral

Sin tratamiento quirúrgico

Lavado/desbridamiento/pulido del cartílago

EN LOS DEFECTOS DE GRADO 3-4 Y CON EL INCREMENTO DEL TAMAÑO DEL DEFECTO, SE REQUIEREN TÉCNICAS DE REGENERACIÓN MÁS COMPLEJAS:

Para los defectos de hasta 2 cm2, normalmente no se utiliza ninguna matriz. El tratamiento habitual se basa en una perforación del hueso subcondral, por ej. mediante microfracturas (MFX) o nanofracturas.

Para los defectos de tamaño entre 2 y 12 cm2 se utiliza Cartimaix para la Estimulación de la Médula Ósea inducida por Matriz (MA-MFX) o evoluciones más avanzadas, por ejemplo, NAMIC©.

Para defectos mayores, Cartimaix se usa en procesos de Transplante Autólogo de Condrocitos recubiertos de Colágeno (de sus siglas en inglés CACI).

NANO FX

NAMIC

CACI

Defect size 0 – 2 cm2 2 – 4 cm2 4 – 12 cm2 > 12 cm2

Grade 2

Grade 1

Lavage / Debridement / Cartilage smoothening

No operative treatment

Grade 3 / Grade 4

MFX

CACI

MA-MFX / NAMIC®

MFX

Treatment methods for cartilage regeneration

The choice of current treatment methods for the therapy of traumatic and degenerative cartilage defects is based on a scheme dependent on the size of the defect and the ICRS classification (Grade 1-4).

IN GRADE 3-4 DEFECTS AND WITH INCREASING DEFECT SIZE, MORE COMPLEX REGENERATION METHODS ARE REQUIRED:

Healthy Cartilage Grade 4 DefectGrade 1 / Grade 2 Defect Grade 3 Defect

lesion of more than 50% of the cartilage thickness

complete lesion of the cartilage, extending into

subchondral bone

light fissures of the cartilage tissue

• For defect sizes up to 2 cm², usually no matrix is used. The

typical treatment relies on a perforation of the subchondral

bone, e.g. Microfracturing (MFX) or Nanofracturing.

• For defect sizes between 2 and 12 cm² Cartimaix is used

for Matrix-Assisted Bone Marrow Stimulation (MA-MFX) or

advanced developments of this, for example NAMIC®.

• For very large defects Cartimaix is used in Collagen-covered

Autologous Chondrocyte Implantation (CACI) procedures.

Métodos de tratamiento para la regeneración del cartílago

La elección de los métodos de tratamiento actuales para el tratamiento de los defectos cartilaginosos traumáticos y degenerativos se basa en un esquema que depende del tamaño del defecto y la clasificación ICRS (grados 1-4).

Cartílago sanoDefecto de grado 1/grado 2 Fisuras leves del tejido cartilaginoso

Defecto de grado 3 Lesión de más del 50% del grosor del cartílago

Defecto de grado 4 Lesión completa del cartílago con extensión al hueso subcondral

Sin tratamiento quirúrgico

Lavado/desbridamiento/pulido del cartílago

EN LOS DEFECTOS DE GRADO 3-4 Y CON EL INCREMENTO DEL TAMAÑO DEL DEFECTO, SE REQUIEREN TÉCNICAS DE REGENERACIÓN MÁS COMPLEJAS:

Para los defectos de hasta 2 cm2, normalmente no se utiliza ninguna matriz. El tratamiento habitual se basa en una perforación del hueso subcondral, por ej. mediante microfracturas (MFX) o nanofracturas.

Para los defectos de tamaño entre 2 y 12 cm2 se utiliza Cartimaix para la Estimulación de la Médula Ósea inducida por Matriz (MA-MFX) o evoluciones más avanzadas, por ejemplo, NAMIC©.

Para defectos mayores, Cartimaix se usa en procesos de Transplante Autólogo de Condrocitos recubiertos de Colágeno (de sus siglas en inglés CACI). . Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Propuesta algoritmo de tratamiento

CartiNamic está indicado para el tratamiento de lesiones focales de cartílago grado III - IV localizadas en la superficie de la articulación de la rodilla, cadera, tobillo, hombro, codo y mano, de 2 a 4 cm2 y hasta 12 cm2 junto con otras técnicas de cultivo celular. La membrana de recubrimiento actúa reteniendo y dando soporte estructural a las células pluripotenciales contenidas en el coágulo sanguíneo provenientes de la médula subcondral tras la realización de la estimulación mínimamente invasiva del fondo de la lesión mendiante el instrumento de precisión Nano FX.

En casos de lesión osteocondral, se recomienda técnica ANAMIC. ‘Augmented Nanofracture Autologous Matrix Induced Condrogenesis’ o técnica ‘Sandwich’ con aprote de hueso de cresta ilíaca o metafisiario.

Page 5: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

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Tel.: +49 2407 5644-0 | Fax: +49 2407 5644-10 | E-Mail: [email protected]

www.matricel.com | www.cartimaix.comRev

. 091

5

Matricel is a manufacturer of medical devices and starting

materials for pharmaceuticals, which are certified e.g. in

Europe, Canada and the United States and are used as

degradable implants in the field of Regenerative Medicine.

The clinical application spectrum of Matricel products ranges

from orthopedics and trauma surgery to plastic surgery,

dermatology and the dental field.

About Matricel

Cleanroom production at Matricel

Cartimaix is available in the following product sizes and is supplied in double

sterile packaging. Each product contains a Cartimaix membrane and a sterile

aluminium Template in the size 40 mm x 50 mm.

CAR4050

Order information

Ordering and further information on Cartimaix and literature references are available on the internet at www.cartimaix.com or www.matricel.com and by phone +49 (0)2407 - 56 44 20.

Order-No.

Product size

Packaging unit

CAR2530

CAR2530

25 mm x 30 mm

1 Cartimaix Membrane + 1 Template

CAR3040

CAR3040

30 mm x 40 mm

1 Cartimaix Membrane + 1 Template

CAR4050

40 mm x 50 mm

1 Cartimaix Membrane + 1 Template

Aluminium Template

El fabricante, Matricel Matricel es un fabricante de dispositivos médicos y materiales de base para farmacéuticas que están certificados por ej. en Europa, Canadá y Estados Unidos y se usan como implantes degradables en el campo de la medicina regenerativa. El espectro de aplicación clínica de los productos Matricel va desde la cirugía ortopédica y la traumatología hasta la cirugía plástica, la dermatología y el sector dental.

Otra información de interés

Cartimaix está disponible en las siguientes medidas y se suministra en doble embalaje estéril . Cada producto contiene una membrana Cartimaix y una plantilla de aluminio estéril de 40x50 mm

cartinamic cartinamic Fabricación del producto

Matriz estructurada biodegradable de colágeno  

. Des del 2003, Num. 1 en Alemania, con más de 12 años seguimiento publicados

. Protección efectiva del área de regeneración

. Base adherente, estable para formación de nuevo cartílago

. Resistencia a fuerzas abrasiones tangenciales

. Comprobada reabsorción lenta, sin residuos tóxicos

Cartimaix, Matricel. Alemania

Propuesta basada en la Evidencia

&

Instrumento de presión Nano FX

. Estimulación mínimamente invasiva del fondo de hueso subcondral

. Más profundo (9mm) , menos diámetro (1 mm) =

. Más migración células pluripotenciales de médula ósea

. Más rápida recuperación, menor daño fondo hueso

Nano FX, Arthrosurface. USA

cartinamic cartinamic

Administration (FDA) and Communauté Européenne (CE)-approvedapplications.

2. Operative technique

It is recommended that patients receive magnetic resonanceimaging (MRI) scans and standing anteroposterior (a.p.) and lateral ra-diographs of their knee joints. The patella should be X rayed axially, anda 20 degrees flexion projection (Rosenberg profile) should be per-formed to evaluate the main weight bearing zone. An orthoradiogramis helpful if there are clinical hints for a mal-alignment of the leg axis.This should be discussed with the patient as varus or valgus deformitymay impede cartilage regeneration. A correction of the axis in combina-tion with subchondral surgery may be advisable.

Indications for NAMIC© are basically the same as the authors'recommendation for nanofracturing [6]: A symptomatic InternationalCartilage Repair Society (ICRS) grade 4 cartilage lesion, the lesion shouldnot be bigger than four square centimeters and should lie in the weightbearing region of the joint. Kissing lesions should also be excluded as inthe AMIC© procedure. The age limit is not yet determined. The authorsprefer not to set a limit at this time as there is not enough data tosupport any limit.

Surgery on the knee is performedwith the patient supine in an ordi-nary arthroscopy setup. The first step is a diagnostic arthroscopy whichshould verify the pre-operatively suspected lesions. There should be athorough check of the cruciate ligaments as stability of the anteriorcruciate ligament is paramount for joint stability and for the healing ofthe treated cartilage defect.

Possible accompanying lesions of the menisci may be addressed(suture if possible or partial resection if suturing is no longer an option)at the time of arthroscopy.

The cartilage defect is measured with the hook in order to deter-mine the size of the implant. The membrane is a collagen I/III mem-brane of the next generation (Cartimaix, Matricell, Herzogenrath,Germany) which allows much stability and is partially resistant toagglomeration in a wet environment. There are two sides of themembrane. The rough side faces the subchondral bone; the smoothside faces the joint.

With the help of a curette, the defect is debrided and the subchondrallayer is identified.

Nanofracturing is performed, keeping in mind that each hole has adefined length of nine millimeters and a diameter of one millimeter(Fig. 1a and c).

Fibrin glue for the attachment of the membrane may be appliedthrough the nanofracturing awl (Arthrosurface, Franklin, MA, USA)with a special adaptor (Fig. 1b and d). The membrane should be cutprior to the application of the fibrin glue. In an arthroscopically assistedmini-open technique, an aluminum templatemay be used to determinethe size of the defect. The application of fibrin glue and the attachmentof the membrane is best done in a dry environment. This may be eitherperformed arthroscopically or in an arthroscopically assistedmini-opentechnique (Fig. 1b).

In an all-arthroscopic setting (Fig. 1b), the tip of the hook helpsto determine the membrane size. In any case should the smooth sur-face be marked with a sterile pen so recognition inside the joint isfacilitated.

1

a b

c d

Fig. 1. a: Needling of a subchondral defect with the nanofracturing needle applied through a nanofracturing awl. b: Application of fibrin glue through the nanofracturing awl in an all-arthroscopic NAMIC© procedure. Note the collagen membrane (marked blue) in the background (arrow). c: Subchondral one millimeter drill holes penetrating nine millimeters deepafter nanofracturing. Note the gaps between the holes permitting sufficient bridging to prevent subchondral fracture. d: The defect is covered with the collagen I/III membrane whichis fixed with fibrin glue. The purple grid marks the external side of the membrane. The membrane is placed slightly below the level of the adjoining cartilage to prevent its accidentalremoval in motion. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

2 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

The membrane is pressed into the defect (Fig. 1d). It is importantthat the walls of the defect are smooth and clearly defined. The mem-brane should be slightly undersized and beneath the surface of theneighboring cartilage matrix as this will help the membrane to stay inplace. A blunt raspatorium may be helpful to apply full pressure onthe membrane and to fix it in the joint.

Once themembrane is fixed the joint is gentlymoved to see that thecollagen membrane remains in place. Irrigation of the joint is discour-aged as this may almost certainly result in membrane dislocation andremoval of the desired blood clot.

3. Postoperative management and rehabilitation

Recommendation for postoperative rehabilitation after subchondralsurgery is mixed, indicating that this issue is far from being resolved.Most studies evaluating microfracturing recommend partial weightbearing for up to sixweeks [2–4,10,11] or do not address this issue at all.

This partialweight bearingpertains to the possible risk of a compres-sion fracture after microfracturing due to small and ill-defined bonebridges between the V-shaped holes [6] which might not bear enoughweight. Articular remodeling and chondral maturation may take up tosix months so limited weight bearing for a certain amount of time isimportant. Studies show, however [7,8] that the remodeling of thechondral matrix may actually profit from early mobilization using acombination of compression and shear forces. Since there is sufficientbridging between the drilled holes and the holes are straight thereshould be no reason for a subchondral impression fracture (Fig. 1c).The authors recommend an orthosis with unlimited range of motion(ROM) for five days, after this period early mobilization of the joint byphysical therapy. Partial weight bearing should be for two weeks only.For rehabilitation, the authors recommend a skateboard like motiondevice. This is easily accessible by most patients and physiotherapistsand combines ideally compression and shear forces.

4. Discussion

The first mid-term studies on microfracturing and the AMIC©technique show encouraging results, advancing this technology fromexperimental towards clinically applicable [4,5,10,11]. These surgicaltechniques may also be performed arthroscopically [9]. The NAMIC©procedure may also be performed arthroscopically (Fig. 1b).

There are clear statements in the literature [12–14] that differentdrilling techniques and sizes of the drills may lead to improved cartilageregeneration. The deeper the drilling is performed the more MSCs areavailable for cartilage regeneration. Small subchondral drill holes of1.0 mm seem to stimulate a better cartilage regeneration in the sheepmodel [15].

There are theoretically several advantages of theNAMIC© technology:The patient has amuch shorter rehabilitation time allowing earlier returnto daily activity andwork. There seems to be a sufficient defect filling andremodeling of the cartilage surface without subchondral cysts or internalosteophytes (Fig. 2). The procedure is reproducible which is a major ad-vantage in designing and comparing studies. The AMIC technique re-quires microfracturing which may lead to subchondral impressionfractures. Since microfracturing is not a standardized procedure [6],there are many tools with differently shaped and sized tips available formicrofracturing, comparing studies is difficult. The correct size and lengthof subchondral drilling remain under discussion as is the extent ofsubchondral surgery [16]. The potential of autologous subchondralMSCs, however, seems to be increasingly undisputed [17].

Macroscopically and histologically, after nanofracturing andapplication of a collagen I/III membrane, fibrous cartilage forms in con-junction with the existing hyaline cartilage (Fig. 4a and b). After oneyear, the membrane seems to be almost completely dissolved with newgrowth of fibrous cartilage into and eventually replacing it (Fig. 4b).Nanofracturing alone reaches a similar histological result (Fig. 4a). After

one year, MRI scans and arthroscopy yield new cartilage formation(Figs. 2 and 3) and defect closure confirming the theoretical back-ground of subchondral surgery.

Cartilage cells do neither jump nor fall into the defect— they tend torest in theirmatrixwhich they obviously produce, and thematrix needsto be shaped as needed for the joint. This would also prevent the forma-tion of internal osteophytes as these are a sign of excessive matrix for-mation. The perfect motion of the knee joint would be the skateboard-typemovement as this includes weight bearing, shear and compression

Fig. 2.MRI one year after NAMIC medial femoral condyle. Note the regenerated cartilage(arrow).

Fig. 3. One year after NAMIC of a chondral defect of the medial femur condyle. Note thenew car cartilage tissue that filled the defect completely (arrow) but also the progressivedeterioration of the surrounding tissue due to generalized osteoarthritis.

3J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

Am J Sports Med. 2014 Sep;42(9):2178-83. doi: 10.1177/0363546514539345. Epub 2014 Jul 7. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Biant LC1, Bentley G2, Vijayan S2, Skinner JA2, Carrington RW2.

104 pacientes, follow up 10-12 años, grandes defectos, ACI, > 70% survival rate, 98% repetirían el tratamiento

Implante fallido a 10 años: 10 de 58 (17%) grupo ACI y 23 de 42 (55%) grupo mosaicoplastia. Resultado funcional pacientes con implante funcional a 10 años: grupo ACI vs Mosaicoplastia significativamente superior (p = 0.02).

J Bone Joint Surg Br. 2012 Apr;94(4):504-9. doi: 10.1302/0301-620X.94B4.27495. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. Bentley G1, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RW.

Literature1. Biant, L. C., Bentley, G., Vijayan, S., Skinner, J. A. & Carrington,

R. W. J. Long-term Results of Autologous Chondrocyte Implantation

in the Knee for Chronic Chondral and Osteochondral Defects. Am. J.

Sports Med. 42, 2178–83 (2014).

2. Knutsen, G. et al. Autologous chondrocyte implantation compa-

red with microfracture in the knee. A randomized trial. J. Bone Joint

Surg. Am. 86-A, 455–64 (2004).

3. Jäger, M., Feser, T., Denck, H. & Krauspe, R. Proliferation and os-

teogenic differentiation of mesenchymal stem cells cultured onto three

different polymers in vitro. Ann. Biomed. Eng. 33, 1319–32 (2005).

4. Gooding, C. R. et al. A prospective, randomised study comparing

two techniques of autologous chondrocyte implantation for osteo-

chondral defects in the knee: Periosteum covered versus type I/III col-

lagen covered. Knee 13, 203–10 (2006).

5. Chen, J. M., Willers, C., Xu, J., Wang, A. & Zheng, M.-H. Autolo-

gous tenocyte therapy using porcine-derived bioscaffolds for massive

rotator cuff defect in rabbits. Tissue Eng. 13, 1479–91 (2007).

6. Jäger, M. et al. Bone healing and migration of cord blood-derived

stem cells into a critical size femoral defect after xenotransplantation.

J. Bone Miner. Res. 22, 1224–33 (2007).

7. Iwasa, J., Engebretsen, L., Shima, Y. & Ochi, M. Clinical appli-

cation of scaffolds for cartilage tissue engineering. Knee Surg. Sports

Traumatol. Arthrosc. 17, 561–77 (2008).

8. Gomoll, A. H., Probst, C., Farr, J., Cole, B. J. & Minas, T. Use of

a type I/III bilayer collagen membrane decreases reoperation rates for

symptomatic hypertrophy after autologous chondrocyte implantation.

Am. J. Sports Med. 37 Suppl 1, 20S–23S (2009).

9. Brittberg, M. Cell carriers as the next generation of cell therapy for

cartilage repair: a review of the matrix-induced autologous chondrocy-

te implantation procedure. Am. J. Sports Med. 38, 1259–71 (2010).

10. Harris, J. D. et al. Failures, re-operations, and complications after

autologous chondrocyte implantation--a systematic review. Osteoarth-

ritis Cartilage 19, 779–91 (2011).

11. Saris, D. et al. Matrix-Applied Characterized Autologous Cultured

Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospec-

tive Randomized Trial. Am. J. Sports Med. 42, 1384–1394 (2014).

12. Brittberg, M., Price, A., Yu, Q., Kili, S. & Saris, D. Poster: SUMMIT

Trial : Matrix-induced Autologous Chondrocyte Implant versus Microf-

racture at 3 Years. in Poster AAOS Annu. Meet. 2015, Las Vegas,

Nevada (2015).

13. Dhollander, A. A. M. et al. Autologous matrix-induced chondroge-

nesis combined with platelet-rich plasma gel: technical description and

a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19,

536–42 (2010).

14. Gille, J. et al. Cell-Laden and Cell-Free Matrix-Induced Chondro-

genesis versus Microfracture for the Treatment of Articular Cartilage

Defects: A Histological and Biomechanical Study in Sheep. Cartilage 1,

29–42 (2010).

15. Gille, J. et al. Mid-term results of Autologous Matrix-Induced

Chondrogenesis for treatment of focal cartilage defects in the knee.

Knee Surg. Sports Traumatol. Arthrosc. 18, 1456–64 (2010).

16. Anders, S., Volz, M., Frick, H. & Gellissen, J. A Randomized, Con-

trolled Trial Comparing Autologous Matrix-Induced Chondrogenesis

(AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of

2 Centers. Open Orthop. J. 7, 133–43 (2013).

17. Gille, J. et al. Outcome of Autologous Matrix Induced Chondroge-

nesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch.

Orthop. Trauma Surg. 133, 87–93 (2013).

18. Bark, S. et al. Enhanced microfracture techniques in cartilage

knee surgery: Fact or fiction? World J. Orthop. 5, 444–9 (2014).

19. Lee, Y. H. D., Suzer, F. & Thermann, H. Autologous Matrix-In-

duced Chondrogenesis in the Knee: A Review. Cartilage 5, 145–153

(2014).

20. Benthien, J. P. & Behrens, P. Nanofractured autologous matrixin-

duced chondrogenesis (NAMIC©) — Further development of collagen

membrane aided chondrogenesis combined with subchondral need-

ling. Knee (2015). doi:10.1016/j.knee.2015.06.010

21. Benthien, J. P. & Behrens, P. Reviewing subchondral cartilage

surgery: considerations for standardised and outcome predictable car-

tilage remodelling: a technical note. Int. Orthop. 37, 2139–45 (2013).

22. Behrens, P., Varoga, D., Niemeyer, P. & Salzmann, G. Intraopera-

tive biologische Augmentation am Knorpel. Arthroskopie 26, 114–122

(2013).

23. Min, B.-H. et al. Effect of different bone marrow stimulation

techniques (BSTs) on MSCs mobilization. J. Orthop. Res. Off. Publ.

Orthop. Res. Soc. 31, 1814–1819 (2013).

24. Eldracher, M., Orth, P., Cucchiarini, M., Pape, D. & Madry, H.

Small Subchondral Drill Holes Improve Marrow Stimulation of Articular

Cartilage Defects. Am. J. Sports Med. 42, 2741–2750 (2014).

25. Benthien, J. P. & Behrens, P. The treatment of chondral and

osteochondral defects of the knee with autologous matrix-induced

chondrogenesis (AMIC): method description and recent developments.

Knee Surg. Sports Traumatol. Arthrosc. 19, 1316–9 (2011).

26. Piontek, T., Ciemniewska-Gorzela, K., Szulc, A., Naczk, J. &

Słomczykowski, M. All-arthroscopic AMIC procedure for repair of car-

tilage defects of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20,

922–5 (2012).

27. Hunziker, E. B. & Stähli, A. Surgical suturing of articular cartilage

induces osteoarthritis-like changes. Osteoarthritis Cartilage 16, 1067–

73 (2008).

Am J Sports Med. 2014 Sep;42(9):2178-83. doi: 10.1177/0363546514539345. Epub 2014 Jul 7. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Biant LC1, Bentley G2, Vijayan S2, Skinner JA2, Carrington RW2.

104 pacientes, follow up 10-12 años, grandes defectos, ACI, > 70% survival rate, 98% repetirían el tratamiento

Implante fallido a 10 años: 10 de 58 (17%) grupo ACI y 23 de 42 (55%) grupo mosaicoplastia. Resultado funcional pacientes con implante funcional a 10 años: grupo ACI vs Mosaicoplastia significativamente superior (p = 0.02).

J Bone Joint Surg Br. 2012 Apr;94(4):504-9. doi: 10.1302/0301-620X.94B4.27495. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. Bentley G1, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RW.

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic Matriz estructurada biodegradable de colágeno  

. Des del 2003, Num. 1 en Alemania, con más de 12 años seguimiento publicados

. Protección efectiva del área de regeneración

. Base adherente, estable para formación de nuevo cartílago

. Resistencia a fuerzas abrasiones tangenciales

. Comprobada reabsorción lenta, sin residuos tóxicos

Cartimaix, Matricel. Alemania

Propuesta basada en la Evidencia

&

Instrumento de presión Nano FX

. Estimulación mínimamente invasiva del fondo de hueso subcondral

. Más profundo (9mm) , menos diámetro (1 mm) =

. Más migración células pluripotenciales de médula ósea

. Más rápida recuperación, menor daño fondo hueso

Nano FX, Arthrosurface. USA

cartinamic cartinamic

Administration (FDA) and Communauté Européenne (CE)-approvedapplications.

2. Operative technique

It is recommended that patients receive magnetic resonanceimaging (MRI) scans and standing anteroposterior (a.p.) and lateral ra-diographs of their knee joints. The patella should be X rayed axially, anda 20 degrees flexion projection (Rosenberg profile) should be per-formed to evaluate the main weight bearing zone. An orthoradiogramis helpful if there are clinical hints for a mal-alignment of the leg axis.This should be discussed with the patient as varus or valgus deformitymay impede cartilage regeneration. A correction of the axis in combina-tion with subchondral surgery may be advisable.

Indications for NAMIC© are basically the same as the authors'recommendation for nanofracturing [6]: A symptomatic InternationalCartilage Repair Society (ICRS) grade 4 cartilage lesion, the lesion shouldnot be bigger than four square centimeters and should lie in the weightbearing region of the joint. Kissing lesions should also be excluded as inthe AMIC© procedure. The age limit is not yet determined. The authorsprefer not to set a limit at this time as there is not enough data tosupport any limit.

Surgery on the knee is performedwith the patient supine in an ordi-nary arthroscopy setup. The first step is a diagnostic arthroscopy whichshould verify the pre-operatively suspected lesions. There should be athorough check of the cruciate ligaments as stability of the anteriorcruciate ligament is paramount for joint stability and for the healing ofthe treated cartilage defect.

Possible accompanying lesions of the menisci may be addressed(suture if possible or partial resection if suturing is no longer an option)at the time of arthroscopy.

The cartilage defect is measured with the hook in order to deter-mine the size of the implant. The membrane is a collagen I/III mem-brane of the next generation (Cartimaix, Matricell, Herzogenrath,Germany) which allows much stability and is partially resistant toagglomeration in a wet environment. There are two sides of themembrane. The rough side faces the subchondral bone; the smoothside faces the joint.

With the help of a curette, the defect is debrided and the subchondrallayer is identified.

Nanofracturing is performed, keeping in mind that each hole has adefined length of nine millimeters and a diameter of one millimeter(Fig. 1a and c).

Fibrin glue for the attachment of the membrane may be appliedthrough the nanofracturing awl (Arthrosurface, Franklin, MA, USA)with a special adaptor (Fig. 1b and d). The membrane should be cutprior to the application of the fibrin glue. In an arthroscopically assistedmini-open technique, an aluminum templatemay be used to determinethe size of the defect. The application of fibrin glue and the attachmentof the membrane is best done in a dry environment. This may be eitherperformed arthroscopically or in an arthroscopically assistedmini-opentechnique (Fig. 1b).

In an all-arthroscopic setting (Fig. 1b), the tip of the hook helpsto determine the membrane size. In any case should the smooth sur-face be marked with a sterile pen so recognition inside the joint isfacilitated.

1

a b

c d

Fig. 1. a: Needling of a subchondral defect with the nanofracturing needle applied through a nanofracturing awl. b: Application of fibrin glue through the nanofracturing awl in an all-arthroscopic NAMIC© procedure. Note the collagen membrane (marked blue) in the background (arrow). c: Subchondral one millimeter drill holes penetrating nine millimeters deepafter nanofracturing. Note the gaps between the holes permitting sufficient bridging to prevent subchondral fracture. d: The defect is covered with the collagen I/III membrane whichis fixed with fibrin glue. The purple grid marks the external side of the membrane. The membrane is placed slightly below the level of the adjoining cartilage to prevent its accidentalremoval in motion. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

2 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

The membrane is pressed into the defect (Fig. 1d). It is importantthat the walls of the defect are smooth and clearly defined. The mem-brane should be slightly undersized and beneath the surface of theneighboring cartilage matrix as this will help the membrane to stay inplace. A blunt raspatorium may be helpful to apply full pressure onthe membrane and to fix it in the joint.

Once themembrane is fixed the joint is gentlymoved to see that thecollagen membrane remains in place. Irrigation of the joint is discour-aged as this may almost certainly result in membrane dislocation andremoval of the desired blood clot.

3. Postoperative management and rehabilitation

Recommendation for postoperative rehabilitation after subchondralsurgery is mixed, indicating that this issue is far from being resolved.Most studies evaluating microfracturing recommend partial weightbearing for up to sixweeks [2–4,10,11] or do not address this issue at all.

This partialweight bearingpertains to the possible risk of a compres-sion fracture after microfracturing due to small and ill-defined bonebridges between the V-shaped holes [6] which might not bear enoughweight. Articular remodeling and chondral maturation may take up tosix months so limited weight bearing for a certain amount of time isimportant. Studies show, however [7,8] that the remodeling of thechondral matrix may actually profit from early mobilization using acombination of compression and shear forces. Since there is sufficientbridging between the drilled holes and the holes are straight thereshould be no reason for a subchondral impression fracture (Fig. 1c).The authors recommend an orthosis with unlimited range of motion(ROM) for five days, after this period early mobilization of the joint byphysical therapy. Partial weight bearing should be for two weeks only.For rehabilitation, the authors recommend a skateboard like motiondevice. This is easily accessible by most patients and physiotherapistsand combines ideally compression and shear forces.

4. Discussion

The first mid-term studies on microfracturing and the AMIC©technique show encouraging results, advancing this technology fromexperimental towards clinically applicable [4,5,10,11]. These surgicaltechniques may also be performed arthroscopically [9]. The NAMIC©procedure may also be performed arthroscopically (Fig. 1b).

There are clear statements in the literature [12–14] that differentdrilling techniques and sizes of the drills may lead to improved cartilageregeneration. The deeper the drilling is performed the more MSCs areavailable for cartilage regeneration. Small subchondral drill holes of1.0 mm seem to stimulate a better cartilage regeneration in the sheepmodel [15].

There are theoretically several advantages of theNAMIC© technology:The patient has amuch shorter rehabilitation time allowing earlier returnto daily activity andwork. There seems to be a sufficient defect filling andremodeling of the cartilage surface without subchondral cysts or internalosteophytes (Fig. 2). The procedure is reproducible which is a major ad-vantage in designing and comparing studies. The AMIC technique re-quires microfracturing which may lead to subchondral impressionfractures. Since microfracturing is not a standardized procedure [6],there are many tools with differently shaped and sized tips available formicrofracturing, comparing studies is difficult. The correct size and lengthof subchondral drilling remain under discussion as is the extent ofsubchondral surgery [16]. The potential of autologous subchondralMSCs, however, seems to be increasingly undisputed [17].

Macroscopically and histologically, after nanofracturing andapplication of a collagen I/III membrane, fibrous cartilage forms in con-junction with the existing hyaline cartilage (Fig. 4a and b). After oneyear, the membrane seems to be almost completely dissolved with newgrowth of fibrous cartilage into and eventually replacing it (Fig. 4b).Nanofracturing alone reaches a similar histological result (Fig. 4a). After

one year, MRI scans and arthroscopy yield new cartilage formation(Figs. 2 and 3) and defect closure confirming the theoretical back-ground of subchondral surgery.

Cartilage cells do neither jump nor fall into the defect— they tend torest in theirmatrixwhich they obviously produce, and thematrix needsto be shaped as needed for the joint. This would also prevent the forma-tion of internal osteophytes as these are a sign of excessive matrix for-mation. The perfect motion of the knee joint would be the skateboard-typemovement as this includes weight bearing, shear and compression

Fig. 2.MRI one year after NAMIC medial femoral condyle. Note the regenerated cartilage(arrow).

Fig. 3. One year after NAMIC of a chondral defect of the medial femur condyle. Note thenew car cartilage tissue that filled the defect completely (arrow) but also the progressivedeterioration of the surrounding tissue due to generalized osteoarthritis.

3J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

Am J Sports Med. 2014 Sep;42(9):2178-83. doi: 10.1177/0363546514539345. Epub 2014 Jul 7. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Biant LC1, Bentley G2, Vijayan S2, Skinner JA2, Carrington RW2.

104 pacientes, follow up 10-12 años, grandes defectos, ACI, > 70% survival rate, 98% repetirían el tratamiento

Implante fallido a 10 años: 10 de 58 (17%) grupo ACI y 23 de 42 (55%) grupo mosaicoplastia. Resultado funcional pacientes con implante funcional a 10 años: grupo ACI vs Mosaicoplastia significativamente superior (p = 0.02).

J Bone Joint Surg Br. 2012 Apr;94(4):504-9. doi: 10.1302/0301-620X.94B4.27495. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. Bentley G1, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RW.

Literature1. Biant, L. C., Bentley, G., Vijayan, S., Skinner, J. A. & Carrington,

R. W. J. Long-term Results of Autologous Chondrocyte Implantation

in the Knee for Chronic Chondral and Osteochondral Defects. Am. J.

Sports Med. 42, 2178–83 (2014).

2. Knutsen, G. et al. Autologous chondrocyte implantation compa-

red with microfracture in the knee. A randomized trial. J. Bone Joint

Surg. Am. 86-A, 455–64 (2004).

3. Jäger, M., Feser, T., Denck, H. & Krauspe, R. Proliferation and os-

teogenic differentiation of mesenchymal stem cells cultured onto three

different polymers in vitro. Ann. Biomed. Eng. 33, 1319–32 (2005).

4. Gooding, C. R. et al. A prospective, randomised study comparing

two techniques of autologous chondrocyte implantation for osteo-

chondral defects in the knee: Periosteum covered versus type I/III col-

lagen covered. Knee 13, 203–10 (2006).

5. Chen, J. M., Willers, C., Xu, J., Wang, A. & Zheng, M.-H. Autolo-

gous tenocyte therapy using porcine-derived bioscaffolds for massive

rotator cuff defect in rabbits. Tissue Eng. 13, 1479–91 (2007).

6. Jäger, M. et al. Bone healing and migration of cord blood-derived

stem cells into a critical size femoral defect after xenotransplantation.

J. Bone Miner. Res. 22, 1224–33 (2007).

7. Iwasa, J., Engebretsen, L., Shima, Y. & Ochi, M. Clinical appli-

cation of scaffolds for cartilage tissue engineering. Knee Surg. Sports

Traumatol. Arthrosc. 17, 561–77 (2008).

8. Gomoll, A. H., Probst, C., Farr, J., Cole, B. J. & Minas, T. Use of

a type I/III bilayer collagen membrane decreases reoperation rates for

symptomatic hypertrophy after autologous chondrocyte implantation.

Am. J. Sports Med. 37 Suppl 1, 20S–23S (2009).

9. Brittberg, M. Cell carriers as the next generation of cell therapy for

cartilage repair: a review of the matrix-induced autologous chondrocy-

te implantation procedure. Am. J. Sports Med. 38, 1259–71 (2010).

10. Harris, J. D. et al. Failures, re-operations, and complications after

autologous chondrocyte implantation--a systematic review. Osteoarth-

ritis Cartilage 19, 779–91 (2011).

11. Saris, D. et al. Matrix-Applied Characterized Autologous Cultured

Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospec-

tive Randomized Trial. Am. J. Sports Med. 42, 1384–1394 (2014).

12. Brittberg, M., Price, A., Yu, Q., Kili, S. & Saris, D. Poster: SUMMIT

Trial : Matrix-induced Autologous Chondrocyte Implant versus Microf-

racture at 3 Years. in Poster AAOS Annu. Meet. 2015, Las Vegas,

Nevada (2015).

13. Dhollander, A. A. M. et al. Autologous matrix-induced chondroge-

nesis combined with platelet-rich plasma gel: technical description and

a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19,

536–42 (2010).

14. Gille, J. et al. Cell-Laden and Cell-Free Matrix-Induced Chondro-

genesis versus Microfracture for the Treatment of Articular Cartilage

Defects: A Histological and Biomechanical Study in Sheep. Cartilage 1,

29–42 (2010).

15. Gille, J. et al. Mid-term results of Autologous Matrix-Induced

Chondrogenesis for treatment of focal cartilage defects in the knee.

Knee Surg. Sports Traumatol. Arthrosc. 18, 1456–64 (2010).

16. Anders, S., Volz, M., Frick, H. & Gellissen, J. A Randomized, Con-

trolled Trial Comparing Autologous Matrix-Induced Chondrogenesis

(AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of

2 Centers. Open Orthop. J. 7, 133–43 (2013).

17. Gille, J. et al. Outcome of Autologous Matrix Induced Chondroge-

nesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch.

Orthop. Trauma Surg. 133, 87–93 (2013).

18. Bark, S. et al. Enhanced microfracture techniques in cartilage

knee surgery: Fact or fiction? World J. Orthop. 5, 444–9 (2014).

19. Lee, Y. H. D., Suzer, F. & Thermann, H. Autologous Matrix-In-

duced Chondrogenesis in the Knee: A Review. Cartilage 5, 145–153

(2014).

20. Benthien, J. P. & Behrens, P. Nanofractured autologous matrixin-

duced chondrogenesis (NAMIC©) — Further development of collagen

membrane aided chondrogenesis combined with subchondral need-

ling. Knee (2015). doi:10.1016/j.knee.2015.06.010

21. Benthien, J. P. & Behrens, P. Reviewing subchondral cartilage

surgery: considerations for standardised and outcome predictable car-

tilage remodelling: a technical note. Int. Orthop. 37, 2139–45 (2013).

22. Behrens, P., Varoga, D., Niemeyer, P. & Salzmann, G. Intraopera-

tive biologische Augmentation am Knorpel. Arthroskopie 26, 114–122

(2013).

23. Min, B.-H. et al. Effect of different bone marrow stimulation

techniques (BSTs) on MSCs mobilization. J. Orthop. Res. Off. Publ.

Orthop. Res. Soc. 31, 1814–1819 (2013).

24. Eldracher, M., Orth, P., Cucchiarini, M., Pape, D. & Madry, H.

Small Subchondral Drill Holes Improve Marrow Stimulation of Articular

Cartilage Defects. Am. J. Sports Med. 42, 2741–2750 (2014).

25. Benthien, J. P. & Behrens, P. The treatment of chondral and

osteochondral defects of the knee with autologous matrix-induced

chondrogenesis (AMIC): method description and recent developments.

Knee Surg. Sports Traumatol. Arthrosc. 19, 1316–9 (2011).

26. Piontek, T., Ciemniewska-Gorzela, K., Szulc, A., Naczk, J. &

Słomczykowski, M. All-arthroscopic AMIC procedure for repair of car-

tilage defects of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20,

922–5 (2012).

27. Hunziker, E. B. & Stähli, A. Surgical suturing of articular cartilage

induces osteoarthritis-like changes. Osteoarthritis Cartilage 16, 1067–

73 (2008).

Am J Sports Med. 2014 Sep;42(9):2178-83. doi: 10.1177/0363546514539345. Epub 2014 Jul 7. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Biant LC1, Bentley G2, Vijayan S2, Skinner JA2, Carrington RW2.

104 pacientes, follow up 10-12 años, grandes defectos, ACI, > 70% survival rate, 98% repetirían el tratamiento

Implante fallido a 10 años: 10 de 58 (17%) grupo ACI y 23 de 42 (55%) grupo mosaicoplastia. Resultado funcional pacientes con implante funcional a 10 años: grupo ACI vs Mosaicoplastia significativamente superior (p = 0.02).

J Bone Joint Surg Br. 2012 Apr;94(4):504-9. doi: 10.1302/0301-620X.94B4.27495. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. Bentley G1, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RW.

The two sides of Cartimaix in cross-section

The smooth side of Cartimaix The rough side of Cartimaix

Cartimaix – una membrana con dos caras

Cartimaix tiene dos caras: una cara densa y suave y una cara fibrosa abierta y rugosa. El producto combina una función de barrera para proteger el área de regeneración con una base adherente para los condrocitos o las células madre que migran de la médula ósea.

La membrana se implanta con la cara densa y suave mirando hacia el espacio articular. La membrana cubre como un escudo protector el área de tratamiento. Las células y los factores de promoción del crecimiento se mantienen allí donde son necesarios para una regeneración óptima del tejido cartilaginoso.

La cara rugosa se implanta mirando hacia el defecto del cartílago y con su estructura fibrosa abierta sirve como una matriz ideal para la adherencia de las células de regeneración del cartílago.

La cara suave de Cartimaix

Las dos caras de Cartimaix en sección transversal

La cara rugosa de Cartimaix

Características destacadas de Cartimaix

• Material altamente purificado y seguro basado en colágeno porcino y elastina • Manejo y estabilidad mecánica excelente tanto de la membrana seca como de

la membrana rehidratada • Creación de un entorno protegido para la regeneración del cartílago donde se

mantienen las células regeneradoras del cartílago y las sustancias que favorecen la formación del cartílago. Por tanto, no hay pérdida de células ni de sustancias valiosas al espacio articular

• Compatibilidad celular científicamente probada con las células regeneradoras del cartílago

• Comparado con geles, resorción más lenta y mayor resistencia abrasiva a las fuerzas tangenciales

• Remodelación completa del colágeno natural no reticulado durante la regeneración del cartílago sin la liberación de sustancias tóxicas o modificadoras del pH

cartinamic cartinamic

Matricel GmbH | Kaiserstrasse 100, 52134 Herzogenrath, Germany

Tel.: +49 2407 5644-0 | Fax: +49 2407 5644-10 | E-Mail: [email protected]

www.matricel.com | www.cartimaix.comRev

. 091

5

Matricel is a manufacturer of medical devices and starting

materials for pharmaceuticals, which are certified e.g. in

Europe, Canada and the United States and are used as

degradable implants in the field of Regenerative Medicine.

The clinical application spectrum of Matricel products ranges

from orthopedics and trauma surgery to plastic surgery,

dermatology and the dental field.

About Matricel

Cleanroom production at Matricel

Cartimaix is available in the following product sizes and is supplied in double

sterile packaging. Each product contains a Cartimaix membrane and a sterile

aluminium Template in the size 40 mm x 50 mm.

CAR4050

Order information

Ordering and further information on Cartimaix and literature references are available on the internet at www.cartimaix.com or www.matricel.com and by phone +49 (0)2407 - 56 44 20.

Order-No.

Product size

Packaging unit

CAR2530

CAR2530

25 mm x 30 mm

1 Cartimaix Membrane + 1 Template

CAR3040

CAR3040

30 mm x 40 mm

1 Cartimaix Membrane + 1 Template

CAR4050

40 mm x 50 mm

1 Cartimaix Membrane + 1 Template

Aluminium Template

El fabricante, Matricel Matricel es un fabricante de dispositivos médicos y materiales de base para farmacéuticas que están certificados por ej. en Europa, Canadá y Estados Unidos y se usan como implantes degradables en el campo de la medicina regenerativa. El espectro de aplicación clínica de los productos Matricel va desde la cirugía ortopédica y la traumatología hasta la cirugía plástica, la dermatología y el sector dental.

Otra información de interés

Cartimaix está disponible en las siguientes medidas y se suministra en doble embalaje estéril . Cada producto contiene una membrana Cartimaix y una plantilla de aluminio estéril de 40x50 mm

Cartimaix – una membrana con dos caras

Cartimaix tiene dos caras: una cara densa y suave y una cara fibrosa abierta y rugosa. El producto combina una función de barrera para proteger el área de regeneración con una base adherente para los condrocitos o las células madre que migran de la médula ósea.

La membrana se implanta con la cara densa y suave mirando hacia el espacio articular. La membrana cubre como un escudo protector el área de tratamiento. Las células y los factores de promoción del crecimiento se mantienen allí donde son necesarios para una regeneración óptima del tejido cartilaginoso.

La cara rugosa se implanta mirando hacia el defecto del cartílago y con su estructura fibrosa abierta sirve como una matriz ideal para la adherencia de las células de regeneración del cartílago.

La cara suave de Cartimaix

Las dos caras de Cartimaix en sección transversal

La cara rugosa de Cartimaix

Características destacadas de Cartimaix

• Material altamente purificado y seguro basado en colágeno porcino y elastina • Manejo y estabilidad mecánica excelente tanto de la membrana seca como de

la membrana rehidratada • Creación de un entorno protegido para la regeneración del cartílago donde se

mantienen las células regeneradoras del cartílago y las sustancias que favorecen la formación del cartílago. Por tanto, no hay pérdida de células ni de sustancias valiosas al espacio articular

• Compatibilidad celular científicamente probada con las células regeneradoras del cartílago

• Comparado con geles, resorción más lenta y mayor resistencia abrasiva a las fuerzas tangenciales

• Remodelación completa del colágeno natural no reticulado durante la regeneración del cartílago sin la liberación de sustancias tóxicas o modificadoras del pH

Propuesta basada en la Evidencia

Características de la membrana:

‘ Deeper versus shallower elicited greater fill of de cartilage defect with a more hyaline character in the repair matrix’ Chen H, Homann CD et al. J. Orthop Rev. 2011

Complete NanoFx System

9 mm deep

Propuesta basada en la evidencia

Page 6: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

5

cartinamic cartinamic Propuesta basada en la Evidencia

. Nano Fx: Técnica estimulación de la subcondral menos invasiva, precisa y reproducible.

+

. Cartimaix: Estabiliza del coágulo y favorece el asentamiento estructurado y posterior diferenciación de las células madre provenientes de la médula ósea subcondral.

II

. Cartílago ‘Hialine Like’.

Administration (FDA) and Communauté Européenne (CE)-approvedapplications.

2. Operative technique

It is recommended that patients receive magnetic resonanceimaging (MRI) scans and standing anteroposterior (a.p.) and lateral ra-diographs of their knee joints. The patella should be X rayed axially, anda 20 degrees flexion projection (Rosenberg profile) should be per-formed to evaluate the main weight bearing zone. An orthoradiogramis helpful if there are clinical hints for a mal-alignment of the leg axis.This should be discussed with the patient as varus or valgus deformitymay impede cartilage regeneration. A correction of the axis in combina-tion with subchondral surgery may be advisable.

Indications for NAMIC© are basically the same as the authors'recommendation for nanofracturing [6]: A symptomatic InternationalCartilage Repair Society (ICRS) grade 4 cartilage lesion, the lesion shouldnot be bigger than four square centimeters and should lie in the weightbearing region of the joint. Kissing lesions should also be excluded as inthe AMIC© procedure. The age limit is not yet determined. The authorsprefer not to set a limit at this time as there is not enough data tosupport any limit.

Surgery on the knee is performedwith the patient supine in an ordi-nary arthroscopy setup. The first step is a diagnostic arthroscopy whichshould verify the pre-operatively suspected lesions. There should be athorough check of the cruciate ligaments as stability of the anteriorcruciate ligament is paramount for joint stability and for the healing ofthe treated cartilage defect.

Possible accompanying lesions of the menisci may be addressed(suture if possible or partial resection if suturing is no longer an option)at the time of arthroscopy.

The cartilage defect is measured with the hook in order to deter-mine the size of the implant. The membrane is a collagen I/III mem-brane of the next generation (Cartimaix, Matricell, Herzogenrath,Germany) which allows much stability and is partially resistant toagglomeration in a wet environment. There are two sides of themembrane. The rough side faces the subchondral bone; the smoothside faces the joint.

With the help of a curette, the defect is debrided and the subchondrallayer is identified.

Nanofracturing is performed, keeping in mind that each hole has adefined length of nine millimeters and a diameter of one millimeter(Fig. 1a and c).

Fibrin glue for the attachment of the membrane may be appliedthrough the nanofracturing awl (Arthrosurface, Franklin, MA, USA)with a special adaptor (Fig. 1b and d). The membrane should be cutprior to the application of the fibrin glue. In an arthroscopically assistedmini-open technique, an aluminum templatemay be used to determinethe size of the defect. The application of fibrin glue and the attachmentof the membrane is best done in a dry environment. This may be eitherperformed arthroscopically or in an arthroscopically assistedmini-opentechnique (Fig. 1b).

In an all-arthroscopic setting (Fig. 1b), the tip of the hook helpsto determine the membrane size. In any case should the smooth sur-face be marked with a sterile pen so recognition inside the joint isfacilitated.

1

a b

c d

Fig. 1. a: Needling of a subchondral defect with the nanofracturing needle applied through a nanofracturing awl. b: Application of fibrin glue through the nanofracturing awl in an all-arthroscopic NAMIC© procedure. Note the collagen membrane (marked blue) in the background (arrow). c: Subchondral one millimeter drill holes penetrating nine millimeters deepafter nanofracturing. Note the gaps between the holes permitting sufficient bridging to prevent subchondral fracture. d: The defect is covered with the collagen I/III membrane whichis fixed with fibrin glue. The purple grid marks the external side of the membrane. The membrane is placed slightly below the level of the adjoining cartilage to prevent its accidentalremoval in motion. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

2 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

forces. In nanofracturing, the drilled holes are always nine millimetersdeep and one millimeter wide, so the results should be reproducible.The risk for a subchondral fracture is low. As this proceduremay be per-formed all arthroscopically with the help of an awl the trauma for thepatient ismuch lower than in the traditional AMIC technique. It is desir-able to have reproducible methods for cartilage regeneration so studiesmay be designed, performed and compared in a betterway. There is alsoan increasing need to prove the efficiency of new operativemethods forreimbursement purposes for health insurance companies. This is bestdone by standardized methods where several independent studiesmay be compared.

There are some disadvantages: The development of differentawls for application in the knee, hip and shoulder joint is chal-lenging. The needle for nanofracturing should be flexible butmay not always be applied at the correct angle. Sometimes a needletends to bend to the side instead of penetration the subchondral bone.Care should be taken to fix the nanofracturing awl at the correct angleas there is considerable risk that the wire may slip and perforate sur-rounding cartilage.

We still do not know if a nine millimeters deep penetration of thesubchondral room is sufficient. At this time, the nine millimeters limit isset by the Nitinol material of the needle. The stability of the needle alsoneeds to be ascertained as needle breaking would lead to unnecessarytrauma for the patient. The advantage of 1.0 mm wire diameter isconfirmed by animal studies [15].

5. Conclusion

The NAMIC© procedure further develops the collagen membraneinduced chondrogenesis procedures (AMIC©). Small holes in combina-tion with subchondral needling and a stable, reliable membrane couldprovide a method to achieve reproducible results and a standardizedprocedure. The latest theoretical results in cartilage regeneration inthe literature seem to confirm this further development. The postoper-ative rehabilitation is shortened by 2/3 as compared to the traditionalAMIC© procedure. First results are encouraging and compared well tothe AMIC© procedure. Further studies, however, are needed, especiallyin a proposed shortened rehabilitation protocol. As in all regenerativecartilage methods, general osteoarthritis of a joint may not be stoppedand one problem that has been solvedmay just be followed by another.After two years of application, the authors observe that there seems tobe a worse outcome after NAMIC© in patients with osteoarthritis ascompared to patients with post-traumatic defects.

The authors are currently planning a study concerning the follow-upof their NAMIC© patients. From preliminary encouraging observationswe postulate that the NAMIC©-procedure will compare well to theAMIC© procedure with the advantages of a much shorter rehab timeand a comparability to other methods.

Acknowledgments

The authors would like to sincerely thank the patients treated withNAMIC© from Davos, Switzerland, for their kind permission to havetheir data published.

References

[1] Makris EA, Gomoll AH, Malizos KN, Athanasiou KA. Repair and tissue engineeringtechniques for articular cartilage. Nat Rev Rheumatol 2014. http://dx.doi.org/10.1038/nrrheum.2014.157 (Epub ahead of print).

[2] Benthien JP, Behrens P. The treatment of chondral and osteochondral defects of theknee with autologous matrix-induced chondrogenesis (AMIC): method descriptionand recent developments. Knee Surg Sports Traumatol 2011;19:1316–9. http://dx.doi.org/10.1007/s00167-010-1356-1.

[3] Steadman JR, Rodkey WG, Rodrigo JJ. “Microfracture”: surgical technique and reha-bilitation to treat chondral defects. Clin Orthop Relat Res 2001;391:S362–9.

[4] Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-term results ofautologous matrix induced chondrogenesis (AMIC). Knee Surg Sports TraumatolArthrosc 2010;18:1456–64.

[5] Lee YHDL, Suzer F, Thermann H. Autologous matrix induced chondrogenesis in theknee: a review. Cartilage 2014;5(3):145–53.

[6] Benthien JP, Behrens P. Reviewing subchondral cartilage surgery: considerations forstandardized and outcome predictable cartilage remodellling. Int Orthop 2013;37:2139–45.

[7] Wang N, Grad S, Stoddart MJ, Niemeyer P, Reising K, Schmal H, et al. Particulate car-tilage under bioreactor induced compression-shear. Int Orthop 2014;38(5):1105–11.

[8] Schaetti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, et al. A combination ofshear and dynamic compression leads to mechanically induced chondrogenesis ofhuman mesenchymal stem cells. Eur Cell Mater 2011;22:214–25.

[9] Piontek T, Ciemniewska-Gorzela K, Szulc A, Naczk J, Slomczykowski M. All-arthroscopic AMIC procedure for repair of cartilage defects. Knee Surg SportsTraumatol Arthrosc 2012;20:922–5.

[10] Asik M, Ciftci F, Sen C, Erdil M, Atalar A. The microfracture technique for the treat-ment of full-thickness articular lesions of the knee: midterm results. Arthroscopy2008;24(11):1214–20. http://dx.doi.org/10.1016/j.arthro.2008.06.015.

[11] Mithoefer K, McAdam T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy ofthe microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 2009;37:2053–63. http://dx.doi.org/10.1177/0363546508328414.

[12] Chen H, Hoemann CD, Sun J, Chevrier A, McKee MD, Shive MS, et al. Depth ofsubchondral perforation influences the outcome of bone marrow stimulation cartilagerepair. J Orthop Res 2011;29(8):1178–84. http://dx.doi.org/10.1002/jor.21386.

a

b

Fig. 4. a. Histology of newly formed fibrous cartilage at the border of hyaline/fibrouscartilage (white arrow) nine months after nanofracturing alone. The black arrow marksthe joint surface. b. Histological picture 12months afterNAMIC©: There seems to be a con-tinuous border of hyaline and fibrous cartilage (white arrow). Fragments of the collagenmembrane may be seen with fibrous cartilage growing into it (black arrow).Photowith kind permission ofDr.M.Germer, Department of Pathology, CantonalHospital,Chur, Switzerland. Photo with kind permission of the Department of Pathology, CantonalHospital, Chur, Switzerland.

4 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

forces. In nanofracturing, the drilled holes are always nine millimetersdeep and one millimeter wide, so the results should be reproducible.The risk for a subchondral fracture is low. As this proceduremay be per-formed all arthroscopically with the help of an awl the trauma for thepatient ismuch lower than in the traditional AMIC technique. It is desir-able to have reproducible methods for cartilage regeneration so studiesmay be designed, performed and compared in a betterway. There is alsoan increasing need to prove the efficiency of new operativemethods forreimbursement purposes for health insurance companies. This is bestdone by standardized methods where several independent studiesmay be compared.

There are some disadvantages: The development of differentawls for application in the knee, hip and shoulder joint is chal-lenging. The needle for nanofracturing should be flexible butmay not always be applied at the correct angle. Sometimes a needletends to bend to the side instead of penetration the subchondral bone.Care should be taken to fix the nanofracturing awl at the correct angleas there is considerable risk that the wire may slip and perforate sur-rounding cartilage.

We still do not know if a nine millimeters deep penetration of thesubchondral room is sufficient. At this time, the nine millimeters limit isset by the Nitinol material of the needle. The stability of the needle alsoneeds to be ascertained as needle breaking would lead to unnecessarytrauma for the patient. The advantage of 1.0 mm wire diameter isconfirmed by animal studies [15].

5. Conclusion

The NAMIC© procedure further develops the collagen membraneinduced chondrogenesis procedures (AMIC©). Small holes in combina-tion with subchondral needling and a stable, reliable membrane couldprovide a method to achieve reproducible results and a standardizedprocedure. The latest theoretical results in cartilage regeneration inthe literature seem to confirm this further development. The postoper-ative rehabilitation is shortened by 2/3 as compared to the traditionalAMIC© procedure. First results are encouraging and compared well tothe AMIC© procedure. Further studies, however, are needed, especiallyin a proposed shortened rehabilitation protocol. As in all regenerativecartilage methods, general osteoarthritis of a joint may not be stoppedand one problem that has been solvedmay just be followed by another.After two years of application, the authors observe that there seems tobe a worse outcome after NAMIC© in patients with osteoarthritis ascompared to patients with post-traumatic defects.

The authors are currently planning a study concerning the follow-upof their NAMIC© patients. From preliminary encouraging observationswe postulate that the NAMIC©-procedure will compare well to theAMIC© procedure with the advantages of a much shorter rehab timeand a comparability to other methods.

Acknowledgments

The authors would like to sincerely thank the patients treated withNAMIC© from Davos, Switzerland, for their kind permission to havetheir data published.

References

[1] Makris EA, Gomoll AH, Malizos KN, Athanasiou KA. Repair and tissue engineeringtechniques for articular cartilage. Nat Rev Rheumatol 2014. http://dx.doi.org/10.1038/nrrheum.2014.157 (Epub ahead of print).

[2] Benthien JP, Behrens P. The treatment of chondral and osteochondral defects of theknee with autologous matrix-induced chondrogenesis (AMIC): method descriptionand recent developments. Knee Surg Sports Traumatol 2011;19:1316–9. http://dx.doi.org/10.1007/s00167-010-1356-1.

[3] Steadman JR, Rodkey WG, Rodrigo JJ. “Microfracture”: surgical technique and reha-bilitation to treat chondral defects. Clin Orthop Relat Res 2001;391:S362–9.

[4] Gille J, Schuseil E, Wimmer J, Gellissen J, Schulz AP, Behrens P. Mid-term results ofautologous matrix induced chondrogenesis (AMIC). Knee Surg Sports TraumatolArthrosc 2010;18:1456–64.

[5] Lee YHDL, Suzer F, Thermann H. Autologous matrix induced chondrogenesis in theknee: a review. Cartilage 2014;5(3):145–53.

[6] Benthien JP, Behrens P. Reviewing subchondral cartilage surgery: considerations forstandardized and outcome predictable cartilage remodellling. Int Orthop 2013;37:2139–45.

[7] Wang N, Grad S, Stoddart MJ, Niemeyer P, Reising K, Schmal H, et al. Particulate car-tilage under bioreactor induced compression-shear. Int Orthop 2014;38(5):1105–11.

[8] Schaetti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, et al. A combination ofshear and dynamic compression leads to mechanically induced chondrogenesis ofhuman mesenchymal stem cells. Eur Cell Mater 2011;22:214–25.

[9] Piontek T, Ciemniewska-Gorzela K, Szulc A, Naczk J, Slomczykowski M. All-arthroscopic AMIC procedure for repair of cartilage defects. Knee Surg SportsTraumatol Arthrosc 2012;20:922–5.

[10] Asik M, Ciftci F, Sen C, Erdil M, Atalar A. The microfracture technique for the treat-ment of full-thickness articular lesions of the knee: midterm results. Arthroscopy2008;24(11):1214–20. http://dx.doi.org/10.1016/j.arthro.2008.06.015.

[11] Mithoefer K, McAdam T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy ofthe microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 2009;37:2053–63. http://dx.doi.org/10.1177/0363546508328414.

[12] Chen H, Hoemann CD, Sun J, Chevrier A, McKee MD, Shive MS, et al. Depth ofsubchondral perforation influences the outcome of bone marrow stimulation cartilagerepair. J Orthop Res 2011;29(8):1178–84. http://dx.doi.org/10.1002/jor.21386.

a

b

Fig. 4. a. Histology of newly formed fibrous cartilage at the border of hyaline/fibrouscartilage (white arrow) nine months after nanofracturing alone. The black arrow marksthe joint surface. b. Histological picture 12months afterNAMIC©: There seems to be a con-tinuous border of hyaline and fibrous cartilage (white arrow). Fragments of the collagenmembrane may be seen with fibrous cartilage growing into it (black arrow).Photowith kind permission ofDr.M.Germer, Department of Pathology, CantonalHospital,Chur, Switzerland. Photo with kind permission of the Department of Pathology, CantonalHospital, Chur, Switzerland.

4 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

Behrens_Bentin_06_2015 The Knee

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic Matriz estructurada biodegradable de colágeno  

. Des del 2003, Num. 1 en Alemania, con más de 12 años seguimiento publicados

. Protección efectiva del área de regeneración

. Base adherente, estable para formación de nuevo cartílago

. Resistencia a fuerzas abrasiones tangenciales

. Comprobada reabsorción lenta, sin residuos tóxicos

Cartimaix, Matricel. Alemania

Propuesta basada en la Evidencia

&

Instrumento de presión Nano FX

. Estimulación mínimamente invasiva del fondo de hueso subcondral

. Más profundo (9mm) , menos diámetro (1 mm) =

. Más migración células pluripotenciales de médula ósea

. Más rápida recuperación, menor daño fondo hueso

Nano FX, Arthrosurface. USA

cartinamic cartinamic

Administration (FDA) and Communauté Européenne (CE)-approvedapplications.

2. Operative technique

It is recommended that patients receive magnetic resonanceimaging (MRI) scans and standing anteroposterior (a.p.) and lateral ra-diographs of their knee joints. The patella should be X rayed axially, anda 20 degrees flexion projection (Rosenberg profile) should be per-formed to evaluate the main weight bearing zone. An orthoradiogramis helpful if there are clinical hints for a mal-alignment of the leg axis.This should be discussed with the patient as varus or valgus deformitymay impede cartilage regeneration. A correction of the axis in combina-tion with subchondral surgery may be advisable.

Indications for NAMIC© are basically the same as the authors'recommendation for nanofracturing [6]: A symptomatic InternationalCartilage Repair Society (ICRS) grade 4 cartilage lesion, the lesion shouldnot be bigger than four square centimeters and should lie in the weightbearing region of the joint. Kissing lesions should also be excluded as inthe AMIC© procedure. The age limit is not yet determined. The authorsprefer not to set a limit at this time as there is not enough data tosupport any limit.

Surgery on the knee is performedwith the patient supine in an ordi-nary arthroscopy setup. The first step is a diagnostic arthroscopy whichshould verify the pre-operatively suspected lesions. There should be athorough check of the cruciate ligaments as stability of the anteriorcruciate ligament is paramount for joint stability and for the healing ofthe treated cartilage defect.

Possible accompanying lesions of the menisci may be addressed(suture if possible or partial resection if suturing is no longer an option)at the time of arthroscopy.

The cartilage defect is measured with the hook in order to deter-mine the size of the implant. The membrane is a collagen I/III mem-brane of the next generation (Cartimaix, Matricell, Herzogenrath,Germany) which allows much stability and is partially resistant toagglomeration in a wet environment. There are two sides of themembrane. The rough side faces the subchondral bone; the smoothside faces the joint.

With the help of a curette, the defect is debrided and the subchondrallayer is identified.

Nanofracturing is performed, keeping in mind that each hole has adefined length of nine millimeters and a diameter of one millimeter(Fig. 1a and c).

Fibrin glue for the attachment of the membrane may be appliedthrough the nanofracturing awl (Arthrosurface, Franklin, MA, USA)with a special adaptor (Fig. 1b and d). The membrane should be cutprior to the application of the fibrin glue. In an arthroscopically assistedmini-open technique, an aluminum templatemay be used to determinethe size of the defect. The application of fibrin glue and the attachmentof the membrane is best done in a dry environment. This may be eitherperformed arthroscopically or in an arthroscopically assistedmini-opentechnique (Fig. 1b).

In an all-arthroscopic setting (Fig. 1b), the tip of the hook helpsto determine the membrane size. In any case should the smooth sur-face be marked with a sterile pen so recognition inside the joint isfacilitated.

1

a b

c d

Fig. 1. a: Needling of a subchondral defect with the nanofracturing needle applied through a nanofracturing awl. b: Application of fibrin glue through the nanofracturing awl in an all-arthroscopic NAMIC© procedure. Note the collagen membrane (marked blue) in the background (arrow). c: Subchondral one millimeter drill holes penetrating nine millimeters deepafter nanofracturing. Note the gaps between the holes permitting sufficient bridging to prevent subchondral fracture. d: The defect is covered with the collagen I/III membrane whichis fixed with fibrin glue. The purple grid marks the external side of the membrane. The membrane is placed slightly below the level of the adjoining cartilage to prevent its accidentalremoval in motion. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

2 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

The membrane is pressed into the defect (Fig. 1d). It is importantthat the walls of the defect are smooth and clearly defined. The mem-brane should be slightly undersized and beneath the surface of theneighboring cartilage matrix as this will help the membrane to stay inplace. A blunt raspatorium may be helpful to apply full pressure onthe membrane and to fix it in the joint.

Once themembrane is fixed the joint is gentlymoved to see that thecollagen membrane remains in place. Irrigation of the joint is discour-aged as this may almost certainly result in membrane dislocation andremoval of the desired blood clot.

3. Postoperative management and rehabilitation

Recommendation for postoperative rehabilitation after subchondralsurgery is mixed, indicating that this issue is far from being resolved.Most studies evaluating microfracturing recommend partial weightbearing for up to sixweeks [2–4,10,11] or do not address this issue at all.

This partialweight bearingpertains to the possible risk of a compres-sion fracture after microfracturing due to small and ill-defined bonebridges between the V-shaped holes [6] which might not bear enoughweight. Articular remodeling and chondral maturation may take up tosix months so limited weight bearing for a certain amount of time isimportant. Studies show, however [7,8] that the remodeling of thechondral matrix may actually profit from early mobilization using acombination of compression and shear forces. Since there is sufficientbridging between the drilled holes and the holes are straight thereshould be no reason for a subchondral impression fracture (Fig. 1c).The authors recommend an orthosis with unlimited range of motion(ROM) for five days, after this period early mobilization of the joint byphysical therapy. Partial weight bearing should be for two weeks only.For rehabilitation, the authors recommend a skateboard like motiondevice. This is easily accessible by most patients and physiotherapistsand combines ideally compression and shear forces.

4. Discussion

The first mid-term studies on microfracturing and the AMIC©technique show encouraging results, advancing this technology fromexperimental towards clinically applicable [4,5,10,11]. These surgicaltechniques may also be performed arthroscopically [9]. The NAMIC©procedure may also be performed arthroscopically (Fig. 1b).

There are clear statements in the literature [12–14] that differentdrilling techniques and sizes of the drills may lead to improved cartilageregeneration. The deeper the drilling is performed the more MSCs areavailable for cartilage regeneration. Small subchondral drill holes of1.0 mm seem to stimulate a better cartilage regeneration in the sheepmodel [15].

There are theoretically several advantages of theNAMIC© technology:The patient has amuch shorter rehabilitation time allowing earlier returnto daily activity andwork. There seems to be a sufficient defect filling andremodeling of the cartilage surface without subchondral cysts or internalosteophytes (Fig. 2). The procedure is reproducible which is a major ad-vantage in designing and comparing studies. The AMIC technique re-quires microfracturing which may lead to subchondral impressionfractures. Since microfracturing is not a standardized procedure [6],there are many tools with differently shaped and sized tips available formicrofracturing, comparing studies is difficult. The correct size and lengthof subchondral drilling remain under discussion as is the extent ofsubchondral surgery [16]. The potential of autologous subchondralMSCs, however, seems to be increasingly undisputed [17].

Macroscopically and histologically, after nanofracturing andapplication of a collagen I/III membrane, fibrous cartilage forms in con-junction with the existing hyaline cartilage (Fig. 4a and b). After oneyear, the membrane seems to be almost completely dissolved with newgrowth of fibrous cartilage into and eventually replacing it (Fig. 4b).Nanofracturing alone reaches a similar histological result (Fig. 4a). After

one year, MRI scans and arthroscopy yield new cartilage formation(Figs. 2 and 3) and defect closure confirming the theoretical back-ground of subchondral surgery.

Cartilage cells do neither jump nor fall into the defect— they tend torest in theirmatrixwhich they obviously produce, and thematrix needsto be shaped as needed for the joint. This would also prevent the forma-tion of internal osteophytes as these are a sign of excessive matrix for-mation. The perfect motion of the knee joint would be the skateboard-typemovement as this includes weight bearing, shear and compression

Fig. 2.MRI one year after NAMIC medial femoral condyle. Note the regenerated cartilage(arrow).

Fig. 3. One year after NAMIC of a chondral defect of the medial femur condyle. Note thenew car cartilage tissue that filled the defect completely (arrow) but also the progressivedeterioration of the surrounding tissue due to generalized osteoarthritis.

3J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

Am J Sports Med. 2014 Sep;42(9):2178-83. doi: 10.1177/0363546514539345. Epub 2014 Jul 7. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Biant LC1, Bentley G2, Vijayan S2, Skinner JA2, Carrington RW2.

104 pacientes, follow up 10-12 años, grandes defectos, ACI, > 70% survival rate, 98% repetirían el tratamiento

Implante fallido a 10 años: 10 de 58 (17%) grupo ACI y 23 de 42 (55%) grupo mosaicoplastia. Resultado funcional pacientes con implante funcional a 10 años: grupo ACI vs Mosaicoplastia significativamente superior (p = 0.02).

J Bone Joint Surg Br. 2012 Apr;94(4):504-9. doi: 10.1302/0301-620X.94B4.27495. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. Bentley G1, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RW.

Literature1. Biant, L. C., Bentley, G., Vijayan, S., Skinner, J. A. & Carrington,

R. W. J. Long-term Results of Autologous Chondrocyte Implantation

in the Knee for Chronic Chondral and Osteochondral Defects. Am. J.

Sports Med. 42, 2178–83 (2014).

2. Knutsen, G. et al. Autologous chondrocyte implantation compa-

red with microfracture in the knee. A randomized trial. J. Bone Joint

Surg. Am. 86-A, 455–64 (2004).

3. Jäger, M., Feser, T., Denck, H. & Krauspe, R. Proliferation and os-

teogenic differentiation of mesenchymal stem cells cultured onto three

different polymers in vitro. Ann. Biomed. Eng. 33, 1319–32 (2005).

4. Gooding, C. R. et al. A prospective, randomised study comparing

two techniques of autologous chondrocyte implantation for osteo-

chondral defects in the knee: Periosteum covered versus type I/III col-

lagen covered. Knee 13, 203–10 (2006).

5. Chen, J. M., Willers, C., Xu, J., Wang, A. & Zheng, M.-H. Autolo-

gous tenocyte therapy using porcine-derived bioscaffolds for massive

rotator cuff defect in rabbits. Tissue Eng. 13, 1479–91 (2007).

6. Jäger, M. et al. Bone healing and migration of cord blood-derived

stem cells into a critical size femoral defect after xenotransplantation.

J. Bone Miner. Res. 22, 1224–33 (2007).

7. Iwasa, J., Engebretsen, L., Shima, Y. & Ochi, M. Clinical appli-

cation of scaffolds for cartilage tissue engineering. Knee Surg. Sports

Traumatol. Arthrosc. 17, 561–77 (2008).

8. Gomoll, A. H., Probst, C., Farr, J., Cole, B. J. & Minas, T. Use of

a type I/III bilayer collagen membrane decreases reoperation rates for

symptomatic hypertrophy after autologous chondrocyte implantation.

Am. J. Sports Med. 37 Suppl 1, 20S–23S (2009).

9. Brittberg, M. Cell carriers as the next generation of cell therapy for

cartilage repair: a review of the matrix-induced autologous chondrocy-

te implantation procedure. Am. J. Sports Med. 38, 1259–71 (2010).

10. Harris, J. D. et al. Failures, re-operations, and complications after

autologous chondrocyte implantation--a systematic review. Osteoarth-

ritis Cartilage 19, 779–91 (2011).

11. Saris, D. et al. Matrix-Applied Characterized Autologous Cultured

Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospec-

tive Randomized Trial. Am. J. Sports Med. 42, 1384–1394 (2014).

12. Brittberg, M., Price, A., Yu, Q., Kili, S. & Saris, D. Poster: SUMMIT

Trial : Matrix-induced Autologous Chondrocyte Implant versus Microf-

racture at 3 Years. in Poster AAOS Annu. Meet. 2015, Las Vegas,

Nevada (2015).

13. Dhollander, A. A. M. et al. Autologous matrix-induced chondroge-

nesis combined with platelet-rich plasma gel: technical description and

a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19,

536–42 (2010).

14. Gille, J. et al. Cell-Laden and Cell-Free Matrix-Induced Chondro-

genesis versus Microfracture for the Treatment of Articular Cartilage

Defects: A Histological and Biomechanical Study in Sheep. Cartilage 1,

29–42 (2010).

15. Gille, J. et al. Mid-term results of Autologous Matrix-Induced

Chondrogenesis for treatment of focal cartilage defects in the knee.

Knee Surg. Sports Traumatol. Arthrosc. 18, 1456–64 (2010).

16. Anders, S., Volz, M., Frick, H. & Gellissen, J. A Randomized, Con-

trolled Trial Comparing Autologous Matrix-Induced Chondrogenesis

(AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of

2 Centers. Open Orthop. J. 7, 133–43 (2013).

17. Gille, J. et al. Outcome of Autologous Matrix Induced Chondroge-

nesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch.

Orthop. Trauma Surg. 133, 87–93 (2013).

18. Bark, S. et al. Enhanced microfracture techniques in cartilage

knee surgery: Fact or fiction? World J. Orthop. 5, 444–9 (2014).

19. Lee, Y. H. D., Suzer, F. & Thermann, H. Autologous Matrix-In-

duced Chondrogenesis in the Knee: A Review. Cartilage 5, 145–153

(2014).

20. Benthien, J. P. & Behrens, P. Nanofractured autologous matrixin-

duced chondrogenesis (NAMIC©) — Further development of collagen

membrane aided chondrogenesis combined with subchondral need-

ling. Knee (2015). doi:10.1016/j.knee.2015.06.010

21. Benthien, J. P. & Behrens, P. Reviewing subchondral cartilage

surgery: considerations for standardised and outcome predictable car-

tilage remodelling: a technical note. Int. Orthop. 37, 2139–45 (2013).

22. Behrens, P., Varoga, D., Niemeyer, P. & Salzmann, G. Intraopera-

tive biologische Augmentation am Knorpel. Arthroskopie 26, 114–122

(2013).

23. Min, B.-H. et al. Effect of different bone marrow stimulation

techniques (BSTs) on MSCs mobilization. J. Orthop. Res. Off. Publ.

Orthop. Res. Soc. 31, 1814–1819 (2013).

24. Eldracher, M., Orth, P., Cucchiarini, M., Pape, D. & Madry, H.

Small Subchondral Drill Holes Improve Marrow Stimulation of Articular

Cartilage Defects. Am. J. Sports Med. 42, 2741–2750 (2014).

25. Benthien, J. P. & Behrens, P. The treatment of chondral and

osteochondral defects of the knee with autologous matrix-induced

chondrogenesis (AMIC): method description and recent developments.

Knee Surg. Sports Traumatol. Arthrosc. 19, 1316–9 (2011).

26. Piontek, T., Ciemniewska-Gorzela, K., Szulc, A., Naczk, J. &

Słomczykowski, M. All-arthroscopic AMIC procedure for repair of car-

tilage defects of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20,

922–5 (2012).

27. Hunziker, E. B. & Stähli, A. Surgical suturing of articular cartilage

induces osteoarthritis-like changes. Osteoarthritis Cartilage 16, 1067–

73 (2008).

Am J Sports Med. 2014 Sep;42(9):2178-83. doi: 10.1177/0363546514539345. Epub 2014 Jul 7. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Biant LC1, Bentley G2, Vijayan S2, Skinner JA2, Carrington RW2.

104 pacientes, follow up 10-12 años, grandes defectos, ACI, > 70% survival rate, 98% repetirían el tratamiento

Implante fallido a 10 años: 10 de 58 (17%) grupo ACI y 23 de 42 (55%) grupo mosaicoplastia. Resultado funcional pacientes con implante funcional a 10 años: grupo ACI vs Mosaicoplastia significativamente superior (p = 0.02).

J Bone Joint Surg Br. 2012 Apr;94(4):504-9. doi: 10.1302/0301-620X.94B4.27495. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. Bentley G1, Biant LC, Vijayan S, Macmull S, Skinner JA, Carrington RW.

Propuesta basada en la evidencia

Page 7: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

Cartimaix – una membrana con dos caras

Cartimaix tiene dos caras: una cara densa y suave y una cara fibrosa abierta y rugosa. El producto combina una función de barrera para proteger el área de regeneración con una base adherente para los condrocitos o las células madre que migran de la médula ósea.

La membrana se implanta con la cara densa y suave mirando hacia el espacio articular. La membrana cubre como un escudo protector el área de tratamiento. Las células y los factores de promoción del crecimiento se mantienen allí donde son necesarios para una regeneración óptima del tejido cartilaginoso.

La cara rugosa se implanta mirando hacia el defecto del cartílago y con su estructura fibrosa abierta sirve como una matriz ideal para la adherencia de las células de regeneración del cartílago.

La cara suave de Cartimaix

Las dos caras de Cartimaix en sección transversal

La cara rugosa de Cartimaix

Características destacadas de Cartimaix

• Material altamente purificado y seguro basado en colágeno porcino y elastina • Manejo y estabilidad mecánica excelente tanto de la membrana seca como de

la membrana rehidratada • Creación de un entorno protegido para la regeneración del cartílago donde se

mantienen las células regeneradoras del cartílago y las sustancias que favorecen la formación del cartílago. Por tanto, no hay pérdida de células ni de sustancias valiosas al espacio articular

• Compatibilidad celular científicamente probada con las células regeneradoras del cartílago

• Comparado con geles, resorción más lenta y mayor resistencia abrasiva a las fuerzas tangenciales

• Remodelación completa del colágeno natural no reticulado durante la regeneración del cartílago sin la liberación de sustancias tóxicas o modificadoras del pH

cartinamic cartinamic

Matricel GmbH | Kaiserstrasse 100, 52134 Herzogenrath, Germany

Tel.: +49 2407 5644-0 | Fax: +49 2407 5644-10 | E-Mail: [email protected]

www.matricel.com | www.cartimaix.comRev

. 091

5

Matricel is a manufacturer of medical devices and starting

materials for pharmaceuticals, which are certified e.g. in

Europe, Canada and the United States and are used as

degradable implants in the field of Regenerative Medicine.

The clinical application spectrum of Matricel products ranges

from orthopedics and trauma surgery to plastic surgery,

dermatology and the dental field.

About Matricel

Cleanroom production at Matricel

Cartimaix is available in the following product sizes and is supplied in double

sterile packaging. Each product contains a Cartimaix membrane and a sterile

aluminium Template in the size 40 mm x 50 mm.

CAR4050

Order information

Ordering and further information on Cartimaix and literature references are available on the internet at www.cartimaix.com or www.matricel.com and by phone +49 (0)2407 - 56 44 20.

Order-No.

Product size

Packaging unit

CAR2530

CAR2530

25 mm x 30 mm

1 Cartimaix Membrane + 1 Template

CAR3040

CAR3040

30 mm x 40 mm

1 Cartimaix Membrane + 1 Template

CAR4050

40 mm x 50 mm

1 Cartimaix Membrane + 1 Template

Aluminium Template

El fabricante, Matricel Matricel es un fabricante de dispositivos médicos y materiales de base para farmacéuticas que están certificados por ej. en Europa, Canadá y Estados Unidos y se usan como implantes degradables en el campo de la medicina regenerativa. El espectro de aplicación clínica de los productos Matricel va desde la cirugía ortopédica y la traumatología hasta la cirugía plástica, la dermatología y el sector dental.

Otra información de interés

Cartimaix está disponible en las siguientes medidas y se suministra en doble embalaje estéril . Cada producto contiene una membrana Cartimaix y una plantilla de aluminio estéril de 40x50 mm

Highly purified and safe material based on porcine

collagen and elastin

Excellent handling and mechanical stability of both the dry

and the rehydrated membrane

Creation of a protected environment for tissue

regeneration where cartilage-regenerating cells and

substances promoting cartilage formation are kept -

consequently no loss of cells and valuable substances to

the joint space

Outstanding Cartimaix features

• Scientifically proven cell compatibility with cartilage-

regenerating cells

• Compared with gels slower resorption and higher

abrasion resistance to tangential forces

• Complete remodeling of the natural, non-crosslinked

collagen during the cartilage regeneration without release

of toxic or pH modifying substances

Cartimaix – una membrana con dos caras

Cartimaix tiene dos caras: una cara densa y suave y una cara fibrosa abierta y rugosa. El producto combina una función de barrera para proteger el área de regeneración con una base adherente para los condrocitos o las células madre que migran de la médula ósea.

La membrana se implanta con la cara densa y suave mirando hacia el espacio articular. La membrana cubre como un escudo protector el área de tratamiento. Las células y los factores de promoción del crecimiento se mantienen allí donde son necesarios para una regeneración óptima del tejido cartilaginoso.

La cara rugosa se implanta mirando hacia el defecto del cartílago y con su estructura fibrosa abierta sirve como una matriz ideal para la adherencia de las células de regeneración del cartílago.

La cara suave de Cartimaix

Las dos caras de Cartimaix en sección transversal

La cara rugosa de Cartimaix

Características destacadas de Cartimaix

• Material altamente purificado y seguro basado en colágeno porcino y elastina • Manejo y estabilidad mecánica excelente tanto de la membrana seca como de

la membrana rehidratada • Creación de un entorno protegido para la regeneración del cartílago donde se

mantienen las células regeneradoras del cartílago y las sustancias que favorecen la formación del cartílago. Por tanto, no hay pérdida de células ni de sustancias valiosas al espacio articular

• Compatibilidad celular científicamente probada con las células regeneradoras del cartílago

• Comparado con geles, resorción más lenta y mayor resistencia abrasiva a las fuerzas tangenciales

• Remodelación completa del colágeno natural no reticulado durante la regeneración del cartílago sin la liberación de sustancias tóxicas o modificadoras del pH

Propuesta basada en la Evidencia

Características de la membrana:

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Cartimaix

Cartimaix / ACI-Maix membrane: Structure

Fibrous side (in case of MACI: cell-seeded side)

Smooth side (facing the joint)

Light microscope Scanning EM

cartinamic cartinamic Propuesta basada en la Evidencia

Características de la membrana:

La matriz presenta un costado denso (apariencia lisa) y un costado fibroso (apariencia rugosa). El costado denso está diseñado para retener los condrocitos autólogos o las células pluripotenciales conteniendo el coágulo dentro de la cavidad del defecto condral y protegiéndolo de la agresividad y movimiento articular, mientras que el costado fibroso permite el cultivo y anclaje de las células regeneradoras del cartílago. El costado denso debe estar orientado a la articulación y el costado fibroso debe estar en contacto con el defecto.

Características de la matriz

Page 8: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

11

Microfracture (4A): Trabecular wall thickness and density increased by apparent bone compression; limited trabecular channel access; channel borders with non-anatomic regularity; microfracture channel margins: Dense, compressed bone deposit (right).

Nanofracture (4B): Trabecular wall thickness and density appears normal; large number of open trabecular channels; anatomic irreg-ularity of trabecular channel borders intact; nanofracture channel margins: Course and fragmented trabecular bone deposits (right).

1mm K-Wire (4C): Trabecular wall thickness and density close to normal; limited trabecular channel access; channel borders with non- anatomic regularity; k-wirechannel margins: Pulverized and dense osseous deposits (right).

4A 4B 4C

ConclusionNanofracture resulted in thin, fragmented cancellous bone channels without rotational heat generation. Compared to

superior bone marrow access with multiple trabecular access channels extending 9mm into subchondral bone.

Nanofracture:Bone Marrow Stimulation in Cartilage Repair Comparing Microfracture, Nanofracture, and K-Wire Perforations

W.R. Walsh, Ph.D.N. Bertollo, Ph.D. D. Schaffner, M.D. R. Oliver, Ph.D.C. Christou, B.ScVet

A. Cruz et al. Nano FX

Propuesta basada en la Evidencia

cartinamic cartinamic

Conclusion

Modo de Actuación: Nano FX

10

Propuesta basada en la Evidencia

cartinamic cartinamic

Modo de Actuación: Nano FX

A New Technique for Improved and Systematic Deep Marrow Stimulation and Subchondral Bone Protection

Nanofracture vs. Microfracture

1 mm diámetro , 9 mm profundidad

1. Reviewing subchondral cartilage surgery: considerations for standardized and outcome predictable cartilage remodeling. Benthien JP, Behrens P. Int Orthop. 2013;37(11):2139-2145.

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

El instrumento de precisión Pleuristik Nano FX permite estimular de forma reproducible, efectiva y mínimamente invasiva el fondo de hueso. Concretamente se consigue un sangrado uniforme y un afloramiento de células madre de la propia médula ósea gracias a la profundidad de las perforaciones de 9mm según publica Chen 2011 JOR 2011. También una más pronta recuperación gracias a la mínima agresión sobre el fondo óseo puesto que el diámetro de las perforaciones es de 1 mm, en línea con lo publicado Eldracher AJS 2014.

Características Nanofractura

Page 9: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

. Inmovilización 24h. A posteriori férula extraíble para dormir o desplazamientos

. 6 semanas carga parcial, combinado con:

. 8 horas/día CPM o ‘Skate Style Sliding Motion’ = movimiento deslizante con patín

Estudios subrayan la importancia de un estímulo biomecánico deslizante para la regeneración y mantenimiento de una operativa superficie articular.

La técnica del patín (Skateboard Sliding) combina: Deslizamiento, Compresión, combinado con carga parcial que optimiza la respuesta reparadora.

cartinamic cartinamic Propuesta protocolo rehabilitación

EXPERT OPINIONS IN JOINT PRESERVATION Published: January 30th, 2016 _________________________________________________________________________________________________________

3

spongiosa was better restored after 1.0-mm drilling with significantly higher bone volume, more and thinner trabeculae, and the bone mineral density was similar to the adjacent subchondral bone. These results were reconfirmed in a recent publication using a custom, stop-controlled, non-rotational awl (5mm deep) comparing 1.0 to 1.2mm diameters.21 While there were no differences on microCT among the two diameters, the histological results of the thinner awls showed a significant improvement of the overall repair tissue quality and surface grading compared to larger awls. The comparative human tissue study by Hoemann et al. reconfirmed these findings showing that thin tapered awl geometries allowed easier perforation of dense bone and produced less bone compaction.19 Similarly, the k-wires used by Eldracher et al., the custom awls used by Orth et al., and the nanofracture needles introduced by Benthien et al. showed a 1mm diameter channel on microCT extending from top to bottom.18,20,21

Subchondral Bone Effects The subchondral needling procedure (Nanofracture, Arthrosurface, Franklin, MA, USA) introduced by Benthien in et al. in 2013 (Figure 1) was in response to the renewed attention to the effects of subchondral bone in cartilage repair.18 The microCT in an ovine model showed multiple open trabecular channels throughout the 9mm deep subchondral bone perforation with a physiological, irregular wall outlining the channel. The trabecular bone structure appeared to have normal thickness and density.18 A custom 1mm thick awl used by Orth et al.21 led to a significant improvement in the overall repair tissue quality, histological surface grading, and regularity compared with larger 1.2mm awls. Both on microCT and histology, the results did not show the typical bone compaction effect reported after the use of traditional microfracture awls.12,16,18,19 Treatment Standardization Subchondral bone needling has opened new pathways for potential improvement in marrow stimulation in particular as they relate to a standardized channel formation and depth, cell recruitment, and the ensuing cartilage quantity and quality.18 Compared to the highly variable, user dependent microfracture awl, nanofracture perforation is standardized with predetermined diameter and depth. Rehabilitation Emerging new evidence from recent publications suggests a change in the postoperative rehabilitation may also be beneficial for cartilage repair. Schatti et al. showed that neither compression nor shear alone was sufficient for the chondrogenic induction of human mesenchymal stem cells.31 However, the application of shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression without affecting hypertrophic and osteogenic markers. Other studies underlined the importance of a sliding-type biomechanical stimulus for the regeneration and maintenance of an operative articular surface.32-34 A skateboard style sliding motion combines shear and compression with partial weightbearing which may optimize the healing response compared to traditional CPM (Figure 2).

Figure 2: Skateboard Active Motion (SAM) Combined compression, shear, and partial weightbearing.

Figure 1: Comparison of Microfracture to Nanofracture. Considerations for standardized and outcome predictable cartilage remodeling: a technical note.18

EXPERT OPINIONS IN JOINT PRESERVATION Published: January 30th, 2016 _________________________________________________________________________________________________________

6

evaluationofthemicrofracturetechnique.AmJSportsMed.2006;34:1413-1418.27. Knutsen G, Drogset JO, Engebretsen L, et al. A randomized trial comparing autologous chondrocyte implantation withmicrofracture:

findingsatfiveyears.JBoneJointSurgAm.2007;89(10):2105-2112.28. MithoeferK,McAdamsT,WilliamsRJ,KreuzPC,MandelbaumBR.Clinicalefficacyofthemicrofracturetechniqueforarticularcartilage

repairintheknee:anevidence-basedsystematicanalysis.AmJSportsMed.2009;37(10):2053-2063.29. MilzS,PutzR.Quantitativemorphologyofthesubchondralplateofthetibialplateau.JAnat.1994Aug;185(Pt1):103-10.30. HurstJM,SteadmanJR,O'BrienL,RodkeyWG,BriggsKK.Rehabilitationfollowingmicrofractureforchondralinjuryintheknee.ClinSports

Med.2010Apr;29(2):257-65,viii.31. Schätti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, Stoddart MJ. A combination of shear and dynamic compression leads to

mechanicallyinducedchondrogenesisofhumanmesenchymalstemcells.EurCellMater.2011Oct11;22:214-25.32. GradS,LoparicM,PeterR,StolzM,AebiU,AliniM.Slidingmotionmodulatesstiffnessand frictioncoefficientat thesurfaceof tissue

engineeredcartilage.OsteoarthritisCartilage.2012Apr;20(4):288-95.33. SchättiOR,MarkováM,TorzilliPA,GalloLM.MechanicalLoadingofCartilageExplantswithCompressionandSlidingMotionModulates

GeneExpressionofLubricinandCatabolicEnzymes.Cartilage.2015Jul;6(3):185-93.34. SchättiOR,GalloLM,TorzilliPA.AModeltoStudyArticularCartilageMechanicalandBiologicalResponsestoSlidingLoads.AnnBiomed

Eng.2015Dec23.[Epubaheadofprint]35. BuckwalterJA,MankinHJ.Articularcartilage:degenerationandosteoarthritis,repair,regeneration,andtransplantation.InstrCourseLect.

1998;47:487-504.Review.36. Gomoll AH, Madry H, Knutsen G, van Dijk N, Seil R, Brittberg M, Kon E. The subchondral bone in articular cartilage repair: current

problemsinthesurgicalmanagement.KneeSurgSportsTraumatolArthrosc.2010Apr;18(4):434-47.

For additional product information, including indications, contraindications, warnings, precautions and potential adverse effects, please visit www.arthrosurface.com. Nanofracture instrumentation is registered with FDA, CE marked, and available in other international markets. 28 Forge Parkway - Franklin, MA 02038 - 1 508 520 3003 - fax: 1 508 528 4604 - www.arthrosurface.com

PN 0020-0412 REV A © 2016 Arthrosurface, Inc. All rights reserved.

EXPERT OPINIONS IN JOINT PRESERVATION Published: January 30th, 2016 _________________________________________________________________________________________________________

6

evaluationofthemicrofracturetechnique.AmJSportsMed.2006;34:1413-1418.27. Knutsen G, Drogset JO, Engebretsen L, et al. A randomized trial comparing autologous chondrocyte implantation withmicrofracture:

findingsatfiveyears.JBoneJointSurgAm.2007;89(10):2105-2112.28. MithoeferK,McAdamsT,WilliamsRJ,KreuzPC,MandelbaumBR.Clinicalefficacyofthemicrofracturetechniqueforarticularcartilage

repairintheknee:anevidence-basedsystematicanalysis.AmJSportsMed.2009;37(10):2053-2063.29. MilzS,PutzR.Quantitativemorphologyofthesubchondralplateofthetibialplateau.JAnat.1994Aug;185(Pt1):103-10.30. HurstJM,SteadmanJR,O'BrienL,RodkeyWG,BriggsKK.Rehabilitationfollowingmicrofractureforchondralinjuryintheknee.ClinSports

Med.2010Apr;29(2):257-65,viii.31. Schätti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, Stoddart MJ. A combination of shear and dynamic compression leads to

mechanicallyinducedchondrogenesisofhumanmesenchymalstemcells.EurCellMater.2011Oct11;22:214-25.32. GradS,LoparicM,PeterR,StolzM,AebiU,AliniM.Slidingmotionmodulatesstiffnessand frictioncoefficientat thesurfaceof tissue

engineeredcartilage.OsteoarthritisCartilage.2012Apr;20(4):288-95.33. SchättiOR,MarkováM,TorzilliPA,GalloLM.MechanicalLoadingofCartilageExplantswithCompressionandSlidingMotionModulates

GeneExpressionofLubricinandCatabolicEnzymes.Cartilage.2015Jul;6(3):185-93.34. SchättiOR,GalloLM,TorzilliPA.AModeltoStudyArticularCartilageMechanicalandBiologicalResponsestoSlidingLoads.AnnBiomed

Eng.2015Dec23.[Epubaheadofprint]35. BuckwalterJA,MankinHJ.Articularcartilage:degenerationandosteoarthritis,repair,regeneration,andtransplantation.InstrCourseLect.

1998;47:487-504.Review.36. Gomoll AH, Madry H, Knutsen G, van Dijk N, Seil R, Brittberg M, Kon E. The subchondral bone in articular cartilage repair: current

problemsinthesurgicalmanagement.KneeSurgSportsTraumatolArthrosc.2010Apr;18(4):434-47.

For additional product information, including indications, contraindications, warnings, precautions and potential adverse effects, please visit www.arthrosurface.com. Nanofracture instrumentation is registered with FDA, CE marked, and available in other international markets. 28 Forge Parkway - Franklin, MA 02038 - 1 508 520 3003 - fax: 1 508 528 4604 - www.arthrosurface.com

PN 0020-0412 REV A © 2016 Arthrosurface, Inc. All rights reserved.

EXPERT OPINIONS IN JOINT PRESERVATION Published: January 30th, 2016 _________________________________________________________________________________________________________

6

evaluationofthemicrofracturetechnique.AmJSportsMed.2006;34:1413-1418.27. Knutsen G, Drogset JO, Engebretsen L, et al. A randomized trial comparing autologous chondrocyte implantation withmicrofracture:

findingsatfiveyears.JBoneJointSurgAm.2007;89(10):2105-2112.28. MithoeferK,McAdamsT,WilliamsRJ,KreuzPC,MandelbaumBR.Clinicalefficacyofthemicrofracturetechniqueforarticularcartilage

repairintheknee:anevidence-basedsystematicanalysis.AmJSportsMed.2009;37(10):2053-2063.29. MilzS,PutzR.Quantitativemorphologyofthesubchondralplateofthetibialplateau.JAnat.1994Aug;185(Pt1):103-10.30. HurstJM,SteadmanJR,O'BrienL,RodkeyWG,BriggsKK.Rehabilitationfollowingmicrofractureforchondralinjuryintheknee.ClinSports

Med.2010Apr;29(2):257-65,viii.31. Schätti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, Stoddart MJ. A combination of shear and dynamic compression leads to

mechanicallyinducedchondrogenesisofhumanmesenchymalstemcells.EurCellMater.2011Oct11;22:214-25.32. GradS,LoparicM,PeterR,StolzM,AebiU,AliniM.Slidingmotionmodulatesstiffnessand frictioncoefficientat thesurfaceof tissue

engineeredcartilage.OsteoarthritisCartilage.2012Apr;20(4):288-95.33. SchättiOR,MarkováM,TorzilliPA,GalloLM.MechanicalLoadingofCartilageExplantswithCompressionandSlidingMotionModulates

GeneExpressionofLubricinandCatabolicEnzymes.Cartilage.2015Jul;6(3):185-93.34. SchättiOR,GalloLM,TorzilliPA.AModeltoStudyArticularCartilageMechanicalandBiologicalResponsestoSlidingLoads.AnnBiomed

Eng.2015Dec23.[Epubaheadofprint]35. BuckwalterJA,MankinHJ.Articularcartilage:degenerationandosteoarthritis,repair,regeneration,andtransplantation.InstrCourseLect.

1998;47:487-504.Review.36. Gomoll AH, Madry H, Knutsen G, van Dijk N, Seil R, Brittberg M, Kon E. The subchondral bone in articular cartilage repair: current

problemsinthesurgicalmanagement.KneeSurgSportsTraumatolArthrosc.2010Apr;18(4):434-47.

For additional product information, including indications, contraindications, warnings, precautions and potential adverse effects, please visit www.arthrosurface.com. Nanofracture instrumentation is registered with FDA, CE marked, and available in other international markets. 28 Forge Parkway - Franklin, MA 02038 - 1 508 520 3003 - fax: 1 508 528 4604 - www.arthrosurface.com

PN 0020-0412 REV A © 2016 Arthrosurface, Inc. All rights reserved.

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Propuesta protocolo rehabilitación

Page 10: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

Detalle Técnica Quirúrgica

cartinamic cartinamic

From Mithoefer et al. JBJS (Am) 88A Sept.2006

6

Nueva Tendencia en Tratamiento de Lesiones Condrales

Guided Bone Marrow Stimulation (GBMS)

6

Nueva Tendencia en Tratamiento de Lesiones Condrales

Guided Bone Marrow Stimulation (GBMS)

2-3mm

Behrens et al. Int. Ortho 37, 2139-45 (2013)

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Una vez localizada la lesión y confirmar la indicación, se procede a debridar el tejido dañado mediante cureta o cucharilla y a definir los bordes verticales mediante bisturí o similar. Tras esta fase inicial, se procede a realizar la estimulación de la médula subcondral mediante el instrumento de precisión Pleuristik Nano FX, generalmente como parte de un procedimiento artroscópico o quirúrgico de mínimo acceso. No se requieren incisiones quirúrgicas específicas o especiales. Se recomienda seguir un patrón espiral para conseguir estimular de forma homogénea el fondo de hueso subcondral, realizando nanoperforaciones distanciadas 2 mm aproximadamente para respetar los puentes de hueso y de 1 mm de diámetro por 9 mm de profundidad para conseguir mayor migración celular. El instrumento de precisión Pleuristik NanoFx se coloca introduciendo primero la punta dentro de la abertura proximal del instrumento de mano Nano Fx. La punta distal del instrumento se coloca luego en el sitio deseado. Un suave golpe con una maza en el contracabezal proximal expuesto del pleuristik es suficiente para conseguir introducirlo a su máxima profundidad. Luego se retira el instrumento de mano NanoFx mediante la lengüeta y se vuelve a colocar repitiendo el proceso hasta conseguir una cobertura / sangrado homogéneo del área de la lesión.

Técnica quirúrgica: Paso a Paso

Page 11: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Una vez preparado el lecho procedemos mediante la plantilla a calcar la lesión y recortamos la forma exacta (3). Próximamente se humedece la matriz en suero salino, se recorta utilizando como guía la plantilla que previamente hemos preparado (4). A posteriori , procedemos a la implantación, orientándola con el costado fibroso hacia el lecho preparado de la lesión y el costado denso hacia a la superficie articular. Para finalizar se recomienda sellar o suturar la membrana con fibrina para evitar avulsión. (5-6).

After removal of the Template, the cut-to-size Cartimaix

membrane can be fitted into the defect area. Due to the

excellent handling characteristics of Cartimaix in rehydrated

state a correction of the pre-cut after fitting is easily possible.

To ensure a secure fixation of the membrane, Cartimaix should

be placed within the healthy, vertical cartilage walls and should

not overlap them.

Please pay attention to Cartimaix orientation during handling.

6. POSITIONING OF CARTIMAIXThe Cartimaix membrane is placed with its

open fibrous side facing the prepared lesion

4 5

6Después de retirar la plantilla, la membrana Cartimaix cortada a medida se puede ajustar al área del defecto. Gracias a las excelentes características de manejo de Cartimaix en estado rehidratado es posible corregir fácilmente el corte previo después del ajuste. Para garantizar una fijación segura de la membrana, Cartimaix debe colocarse dentro de las paredes cartilaginosas verticales sanas y no debe sobreponerse. Por favor, preste atención a la orientación de Cartimaix durante su manejo.

sufficient treatment. In case a defect size larger than 2 cm² is

observed during the arthroscopy, it is recommended to cover

the defect area with a Cartimaix membrane after the sub-

chondral perforation and to prevent the loss of released bone

marrow cells into the joint space.

1

3

2

un tamaño del defecto superior a 2 cm2 durante la artroscopia, se recomienda recubrir el área del defecto con una membrana Cartimaix después de la perforación subcondral y evitar así la pérdida de las células de la médula ósea liberadas al espacio articular.

Behrens_Bentin_06_2015 The Knee

Técnica quirúrgica: Paso a Paso

Page 12: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

cartinamic cartinamic Detalle Técnica Quirúrgica: Arthroscopica

Uniformizando la lesión (X x Y cm) Mosaico con la matriz estructurada

Knee Surg Sports Traumatol Arthrosc. 2012 May; All-arthroscopic AMIC procedure for repair of cartilage defects of the knee Tomasz Piontek,1 Kinga Ciemniewska-Gorzela,1,2 Andrzej Szulc,3 Jakub Naczk,1 and Michał Słomczykowski4

25/05/16 07:57PubMed Central, Fig. 1: Knee Surg Sports Traumatol Arthrosc. 2012 May; 20…: 922–925. Published online 2011 Sep 11. doi: 10.1007/s00167-011-1657-z

Page 1 of 2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3332359/figure/Fig1/

<< Prev Fig. 1 Next >>PMC full text: Knee Surg Sports Traumatol Arthrosc. 2012 May; 20(5): 922–925.Published online 2011 Sep 11. doi: 10.1007/s00167-011-1657-zCopyright/License ► Request permission to reuse

Fig. 1

Knee arthroscopy with fluid irrigation. Joint and cartilage assessment and initial preparation of the cartilagedefect area (a). Final preparation of the injured area with a punch from the Smith and Nephew OBIreconstruction kit. An appropriately sized knife was introduced perpendicularly to the damaged surface (b,c)

Images in this article

KNEE SURGERY, SPORTS TRAUMATOLOGY,ARTHROSCOPY

‘The chondral defect is measured with a gauge. By use of mosaicplasty trephines, a patch with the appropriate measurements to cover the defect is obtained from a type I/III collagen membrane, as described previously. We recommend that the patch be cut 1 mm smaller than the lesion, anticipating that it will expand slightly when in contact with the moisture of the joint’

27

. Para alinear indicaciones y técnica quirúrgica, se propone los siguientes controles mediante imagen y/o vídeo quirúrgico de los puntos clave A,B,C.

arthroscopic cartilage repair approach. Subsequently,the damaged cartilage is debrided with a sharp curette(Fig 1A) and shaver. The calcified layer is removed toallow adequate adhesion of bone marrow cells (Fig 1B).A stable rim of healthy surrounding cartilage should berespected with regard to the containment of the defect(Fig 1C). The surgeon performs the microfractures withan awl, picking holes of 3 to 4 mm in depth at a distanceof 3 to 4 mm (Fig 1D). Subsequently, the leg is lifted toarrange the defect in a horizontal position, and thearthroscopy liquid is drained (Fig 1E). The defect can befurther dried by use of a small swab (Fig 1F). Mean-while, the BST-CarGel is prepared according to themanufacturer’s instructions with 4.5 mL of autologousvenous blood. The BST-CarGel is then injected and thedefect entirely filled (Fig 1G). Leakage of the BST-CarGel must be avoided. After 15 minutes, stable clot-ting of the BST-CarGel is usually accomplished(Fig 1H). An intra-articular drainage (without suction)is inserted, and the arthroscopy portals are closed instandard fashion. The leg is immobilized in extensionfor 24 hours. Helpful advice for this surgical techniqueis summarized in Table 1, and magnetic resonanceimaging results are shown in Fig 2.

DiscussionWe have shown the feasibility of an arthroscopic

application of BST-CarGel in combination withmicrofracture. The less invasive approach could leadto reduced morbidity and a faster recovery. In terms ofeconomic reasons, the minimally invasive approachcould reduce operative times and prove cost-effective.

Nonetheless, the arthroscopic approach is technicaldemanding and not applicable for all defect localiza-tions. In particular, defects of the patella and of theposterior part of the femoral condyles are difficult toaddress because a horizontal position of the defectscan hardly be achieved. Table 2 summarizes theadvantages and disadvantages of the arthroscopicapproach.BST-CarGel seems to be capable of enhancing

microfracture and possibly overcoming some of themajor shortcomings of this technique by stabilizing theblood clot. Unfortunately, to date, only 12 months’follow-up is available for this biomaterial. Furtherclinical studies are therefore required to evaluate thelong-term benefit of enhanced microfracture with BST-CarGel and of the arthroscopic application versus opensurgery.

Fig 1. Key steps of arthroscopic treatment of cartilage lesions with microfracture and BST-CarGel. (A-C) The cartilage defect isdebrided down to the subchondral bone, with removal of the calcified layer, and to a stable rim of healthy cartilage. (D)Microfractures are performed with an awl. (E) The defect is arranged in a horizontal position, and the liquid is drained. (F) Thedefect can be further dried with a swab. (G) The BST-CarGel is injected into the defect and (H) forms a stable clot in the defectafter 15 minutes.

Table 1. Tips for Arthroscopic Treatment With Microfractureand BST-CarGel

Tips Reasons

Thoroughly remove protrudingsynovial tissue to facilitatevisualization of the defect in thehorizontal position.

Compromised visualization and/or contact of synovial tissuewith the lesion site mightimpede application of thebiomaterial.

Debride the damaged cartilagedown to the subchondral bonewith removal of the calcifiedlayer.

Remaining damaged tissue maycompromise repair tissueformation.

Dry the defect with suction orwith a swab.

Dryness of the defect bed is crucialfor adhesion of the BST-CarGel.

e2 M. R. STEINWACHS ET AL.

arthroscopic cartilage repair approach. Subsequently,the damaged cartilage is debrided with a sharp curette(Fig 1A) and shaver. The calcified layer is removed toallow adequate adhesion of bone marrow cells (Fig 1B).A stable rim of healthy surrounding cartilage should berespected with regard to the containment of the defect(Fig 1C). The surgeon performs the microfractures withan awl, picking holes of 3 to 4 mm in depth at a distanceof 3 to 4 mm (Fig 1D). Subsequently, the leg is lifted toarrange the defect in a horizontal position, and thearthroscopy liquid is drained (Fig 1E). The defect can befurther dried by use of a small swab (Fig 1F). Mean-while, the BST-CarGel is prepared according to themanufacturer’s instructions with 4.5 mL of autologousvenous blood. The BST-CarGel is then injected and thedefect entirely filled (Fig 1G). Leakage of the BST-CarGel must be avoided. After 15 minutes, stable clot-ting of the BST-CarGel is usually accomplished(Fig 1H). An intra-articular drainage (without suction)is inserted, and the arthroscopy portals are closed instandard fashion. The leg is immobilized in extensionfor 24 hours. Helpful advice for this surgical techniqueis summarized in Table 1, and magnetic resonanceimaging results are shown in Fig 2.

DiscussionWe have shown the feasibility of an arthroscopic

application of BST-CarGel in combination withmicrofracture. The less invasive approach could leadto reduced morbidity and a faster recovery. In terms ofeconomic reasons, the minimally invasive approachcould reduce operative times and prove cost-effective.

Nonetheless, the arthroscopic approach is technicaldemanding and not applicable for all defect localiza-tions. In particular, defects of the patella and of theposterior part of the femoral condyles are difficult toaddress because a horizontal position of the defectscan hardly be achieved. Table 2 summarizes theadvantages and disadvantages of the arthroscopicapproach.BST-CarGel seems to be capable of enhancing

microfracture and possibly overcoming some of themajor shortcomings of this technique by stabilizing theblood clot. Unfortunately, to date, only 12 months’follow-up is available for this biomaterial. Furtherclinical studies are therefore required to evaluate thelong-term benefit of enhanced microfracture with BST-CarGel and of the arthroscopic application versus opensurgery.

Fig 1. Key steps of arthroscopic treatment of cartilage lesions with microfracture and BST-CarGel. (A-C) The cartilage defect isdebrided down to the subchondral bone, with removal of the calcified layer, and to a stable rim of healthy cartilage. (D)Microfractures are performed with an awl. (E) The defect is arranged in a horizontal position, and the liquid is drained. (F) Thedefect can be further dried with a swab. (G) The BST-CarGel is injected into the defect and (H) forms a stable clot in the defectafter 15 minutes.

Table 1. Tips for Arthroscopic Treatment With Microfractureand BST-CarGel

Tips Reasons

Thoroughly remove protrudingsynovial tissue to facilitatevisualization of the defect in thehorizontal position.

Compromised visualization and/or contact of synovial tissuewith the lesion site mightimpede application of thebiomaterial.

Debride the damaged cartilagedown to the subchondral bonewith removal of the calcifiedlayer.

Remaining damaged tissue maycompromise repair tissueformation.

Dry the defect with suction orwith a swab.

Dryness of the defect bed is crucialfor adhesion of the BST-CarGel.

e2 M. R. STEINWACHS ET AL.

A) Lesión Pre B) + Nano Fx C) + CARTIMAIX

Administration (FDA) and Communauté Européenne (CE)-approvedapplications.

2. Operative technique

It is recommended that patients receive magnetic resonanceimaging (MRI) scans and standing anteroposterior (a.p.) and lateral ra-diographs of their knee joints. The patella should be X rayed axially, anda 20 degrees flexion projection (Rosenberg profile) should be per-formed to evaluate the main weight bearing zone. An orthoradiogramis helpful if there are clinical hints for a mal-alignment of the leg axis.This should be discussed with the patient as varus or valgus deformitymay impede cartilage regeneration. A correction of the axis in combina-tion with subchondral surgery may be advisable.

Indications for NAMIC© are basically the same as the authors'recommendation for nanofracturing [6]: A symptomatic InternationalCartilage Repair Society (ICRS) grade 4 cartilage lesion, the lesion shouldnot be bigger than four square centimeters and should lie in the weightbearing region of the joint. Kissing lesions should also be excluded as inthe AMIC© procedure. The age limit is not yet determined. The authorsprefer not to set a limit at this time as there is not enough data tosupport any limit.

Surgery on the knee is performedwith the patient supine in an ordi-nary arthroscopy setup. The first step is a diagnostic arthroscopy whichshould verify the pre-operatively suspected lesions. There should be athorough check of the cruciate ligaments as stability of the anteriorcruciate ligament is paramount for joint stability and for the healing ofthe treated cartilage defect.

Possible accompanying lesions of the menisci may be addressed(suture if possible or partial resection if suturing is no longer an option)at the time of arthroscopy.

The cartilage defect is measured with the hook in order to deter-mine the size of the implant. The membrane is a collagen I/III mem-brane of the next generation (Cartimaix, Matricell, Herzogenrath,Germany) which allows much stability and is partially resistant toagglomeration in a wet environment. There are two sides of themembrane. The rough side faces the subchondral bone; the smoothside faces the joint.

With the help of a curette, the defect is debrided and the subchondrallayer is identified.

Nanofracturing is performed, keeping in mind that each hole has adefined length of nine millimeters and a diameter of one millimeter(Fig. 1a and c).

Fibrin glue for the attachment of the membrane may be appliedthrough the nanofracturing awl (Arthrosurface, Franklin, MA, USA)with a special adaptor (Fig. 1b and d). The membrane should be cutprior to the application of the fibrin glue. In an arthroscopically assistedmini-open technique, an aluminum templatemay be used to determinethe size of the defect. The application of fibrin glue and the attachmentof the membrane is best done in a dry environment. This may be eitherperformed arthroscopically or in an arthroscopically assistedmini-opentechnique (Fig. 1b).

In an all-arthroscopic setting (Fig. 1b), the tip of the hook helpsto determine the membrane size. In any case should the smooth sur-face be marked with a sterile pen so recognition inside the joint isfacilitated.

1

a b

c d

Fig. 1. a: Needling of a subchondral defect with the nanofracturing needle applied through a nanofracturing awl. b: Application of fibrin glue through the nanofracturing awl in an all-arthroscopic NAMIC© procedure. Note the collagen membrane (marked blue) in the background (arrow). c: Subchondral one millimeter drill holes penetrating nine millimeters deepafter nanofracturing. Note the gaps between the holes permitting sufficient bridging to prevent subchondral fracture. d: The defect is covered with the collagen I/III membrane whichis fixed with fibrin glue. The purple grid marks the external side of the membrane. The membrane is placed slightly below the level of the adjoining cartilage to prevent its accidentalremoval in motion. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

2 J.P. Benthien, P. Behrens / The Knee xxx (2015) xxx–xxx

Please cite this article as: Benthien JP, Behrens P, Nanofractured autologousmatrixinduced chondrogenesis (NAMIC©)— Further development ofcollagen membrane aided chondrogenesi..., Knee (2015), http://dx.doi.org/10.1016/j.knee.2015.06.010

Estudio Prospectivo Multicéntrico: Knee Case Series

Controles Indicación y Técnica

cartinamic cartinamic

Técnica quirúrgica: Por Artroscopia

Page 13: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

Thumble Handle Instrument

PluriStik Guide Wire

Step 1: Assemble & Orient on Lesion

Step 2: Gently tap to depth stop

Step 3: Push Thumble to extract PluriStik. Repeat.

Modo de Actuación: Nano FX en Astrágalo. Tol et al. publican un 45% a 53% de éxito en pacientes con tratamiento conservador

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

cartinamic cartinamic indicaciones: astrágalo

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC

11/03/16 17:01PubMed Central, Fig 1: Arthrosc Tech. 2015 Oct; 4(5): e463–e469. Published online 2015 Sep 21. doi: 10.1016/j.eats.2015.04.006

Page 1 of 2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662088/figure/fig1/

<< Prev Fig 1 Next >>PMC full text: Arthrosc Tech. 2015 Oct; 4(5): e463–e469.Published online 2015 Sep 21. doi: 10.1016/j.eats.2015.04.006Copyright/License ► Request permission to reuse

Fig 1

(A) Chondral defect located in talus. (B) Debridement and chondrectomy. (C) Microfractures. (D)Implantation of collagen matrix.

Images in this article

Arthrosc Tech. 2015 Jun; 4(3): e255–e259

All-Arthroscopic Autologous Matrix-Induced Chondrogenesis for the Treatment of Osteochondral Lesions of the Talus

Federico Giuseppe Usuelli, M.D.,a,∗ Laura de Girolamo, Ph.D.,b Miriam Grassi, M.D.,a Riccardo

D'Ambrosi, M.D.,a Umberto Alfieri Montrasio, M.D.,a and Michele Boga, M.D.a

Am J Sports Med. 2013 Mar;41(3):519-27.Reconstruction of osteochondral lesions of the talus with autologous spongiosa grafts and autologous matrix-induced chondrogenesis.Valderrabano V1, Miska M, Leumann A, Wiewiorski M.

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Indicaciones: Lesiones en astrágalo

Page 14: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Indicaciones: Lesiones condrales en cadera

cartinamic cartinamic indicaciones: Cadera

Bone Joint J. 2015 May;97-B(5):628-35. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Fontana A1, de Girolamo L2.

Int Orthop. 2014 Oct;38(10):2057-64 Five-year results of arthroscopic techniques for the treatment of acetabular chondral lesions in femoroacetabular impingement. Mancini D1, Fontana A.

Arthrosc Tech. 2012 Sep; 1(1): e63–e68. A Novel Technique for Treating Cartilage Defects in the Hip: A Fully Arthroscopic Approach to Using Autologous Matrix-Induced Chondrogenesis Andrea Fontana⁎

11/03/16 16:31PubMed Central, Figure 4: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/figure/fig4/

<< Prev Figure 4 Next >>PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Figure 4

AMIC for treatment of chondral defect in hip. (A) A third-/fourth-degree chondral defect is located on theanterior area of the acetabulum. (B) Debridement and chondrectomy of the area are performed to expose thesubchondral bone. (C) Once the subchondral bone is fully exposed, microfracturing is performed. (D)Bleeding of the area is checked after microfracturing. (E) The Chondro-Gide matrix is inserted and appliedto cover the defect. The smooth surface of the matrix is marked with lines to ensure that the rough surfacefaces the subchondral bone.

Images in this article

Click on the image to see a larger version.

11/03/16 16:32PubMed Central, Table 2: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/table/tbl2/

PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Table 2

Postoperative Rehabilitation After Arthroscopic Hip AMIC

1 d Postoperatively 2 d to <4 wk

Postoperatively

4 wk to <6 mo

Postoperatively

6 mo to <1 yr

Postoperatively

1 yr

Postoperatively

Load bearing None None Partial load bearingup to 7 wk;afterward, full

Full Full

Mobilization Continuous passivemotion at 60° of hipflexion

Regain step-wise fullrange of motion

No restriction No restriction No restriction

Physiotherapyand sport

No sporting activitiesIsotonic and isometricquadriceps exercises

No sporting activitiesActive and passivephysiotherapy

Light sportingactivities (e.g.,swimming andcycling)

Jogging Full return tosports

. Mínimamente invasivo, 1 procedimiento, tratamiento base estimulación subcondral, protección coágulo y ‘Cambra Bioactiva’, se reduce hospitalización y más rápida recuperación. Coste-Efectivo.

cartinamic cartinamic indicaciones: Cadera

Bone Joint J. 2015 May;97-B(5):628-35. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Fontana A1, de Girolamo L2.

Int Orthop. 2014 Oct;38(10):2057-64 Five-year results of arthroscopic techniques for the treatment of acetabular chondral lesions in femoroacetabular impingement. Mancini D1, Fontana A.

Arthrosc Tech. 2012 Sep; 1(1): e63–e68. A Novel Technique for Treating Cartilage Defects in the Hip: A Fully Arthroscopic Approach to Using Autologous Matrix-Induced Chondrogenesis Andrea Fontana⁎

11/03/16 16:31PubMed Central, Figure 4: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/figure/fig4/

<< Prev Figure 4 Next >>PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Figure 4

AMIC for treatment of chondral defect in hip. (A) A third-/fourth-degree chondral defect is located on theanterior area of the acetabulum. (B) Debridement and chondrectomy of the area are performed to expose thesubchondral bone. (C) Once the subchondral bone is fully exposed, microfracturing is performed. (D)Bleeding of the area is checked after microfracturing. (E) The Chondro-Gide matrix is inserted and appliedto cover the defect. The smooth surface of the matrix is marked with lines to ensure that the rough surfacefaces the subchondral bone.

Images in this article

Click on the image to see a larger version.

11/03/16 16:32PubMed Central, Table 2: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/table/tbl2/

PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Table 2

Postoperative Rehabilitation After Arthroscopic Hip AMIC

1 d Postoperatively 2 d to <4 wk

Postoperatively

4 wk to <6 mo

Postoperatively

6 mo to <1 yr

Postoperatively

1 yr

Postoperatively

Load bearing None None Partial load bearingup to 7 wk;afterward, full

Full Full

Mobilization Continuous passivemotion at 60° of hipflexion

Regain step-wise fullrange of motion

No restriction No restriction No restriction

Physiotherapyand sport

No sporting activitiesIsotonic and isometricquadriceps exercises

No sporting activitiesActive and passivephysiotherapy

Light sportingactivities (e.g.,swimming andcycling)

Jogging Full return tosports

. Mínimamente invasivo, 1 procedimiento, tratamiento base estimulación subcondral, protección coágulo y ‘Cambra Bioactiva’, se reduce hospitalización y más rápida recuperación. Coste-Efectivo.

cartinamic cartinamic indicaciones: Cadera

Bone Joint J. 2015 May;97-B(5):628-35. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Fontana A1, de Girolamo L2.

Int Orthop. 2014 Oct;38(10):2057-64 Five-year results of arthroscopic techniques for the treatment of acetabular chondral lesions in femoroacetabular impingement. Mancini D1, Fontana A.

Arthrosc Tech. 2012 Sep; 1(1): e63–e68. A Novel Technique for Treating Cartilage Defects in the Hip: A Fully Arthroscopic Approach to Using Autologous Matrix-Induced Chondrogenesis Andrea Fontana⁎

11/03/16 16:31PubMed Central, Figure 4: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/figure/fig4/

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Figure 4

AMIC for treatment of chondral defect in hip. (A) A third-/fourth-degree chondral defect is located on theanterior area of the acetabulum. (B) Debridement and chondrectomy of the area are performed to expose thesubchondral bone. (C) Once the subchondral bone is fully exposed, microfracturing is performed. (D)Bleeding of the area is checked after microfracturing. (E) The Chondro-Gide matrix is inserted and appliedto cover the defect. The smooth surface of the matrix is marked with lines to ensure that the rough surfacefaces the subchondral bone.

Images in this article

Click on the image to see a larger version.

11/03/16 16:32PubMed Central, Table 2: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/table/tbl2/

PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Table 2

Postoperative Rehabilitation After Arthroscopic Hip AMIC

1 d Postoperatively 2 d to <4 wk

Postoperatively

4 wk to <6 mo

Postoperatively

6 mo to <1 yr

Postoperatively

1 yr

Postoperatively

Load bearing None None Partial load bearingup to 7 wk;afterward, full

Full Full

Mobilization Continuous passivemotion at 60° of hipflexion

Regain step-wise fullrange of motion

No restriction No restriction No restriction

Physiotherapyand sport

No sporting activitiesIsotonic and isometricquadriceps exercises

No sporting activitiesActive and passivephysiotherapy

Light sportingactivities (e.g.,swimming andcycling)

Jogging Full return tosports

. Mínimamente invasivo, 1 procedimiento, tratamiento base estimulación subcondral, protección coágulo y ‘Cambra Bioactiva’, se reduce hospitalización y más rápida recuperación. Coste-Efectivo.

cartinamic cartinamic indicaciones: Cadera

Bone Joint J. 2015 May;97-B(5):628-35. Sustained five-year benefit of autologous matrix-induced chondrogenesis for femoral acetabular impingement-induced chondral lesions compared with microfracture treatment. Fontana A1, de Girolamo L2.

Int Orthop. 2014 Oct;38(10):2057-64 Five-year results of arthroscopic techniques for the treatment of acetabular chondral lesions in femoroacetabular impingement. Mancini D1, Fontana A.

Arthrosc Tech. 2012 Sep; 1(1): e63–e68. A Novel Technique for Treating Cartilage Defects in the Hip: A Fully Arthroscopic Approach to Using Autologous Matrix-Induced Chondrogenesis Andrea Fontana⁎

11/03/16 16:31PubMed Central, Figure 4: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/figure/fig4/

<< Prev Figure 4 Next >>PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Figure 4

AMIC for treatment of chondral defect in hip. (A) A third-/fourth-degree chondral defect is located on theanterior area of the acetabulum. (B) Debridement and chondrectomy of the area are performed to expose thesubchondral bone. (C) Once the subchondral bone is fully exposed, microfracturing is performed. (D)Bleeding of the area is checked after microfracturing. (E) The Chondro-Gide matrix is inserted and appliedto cover the defect. The smooth surface of the matrix is marked with lines to ensure that the rough surfacefaces the subchondral bone.

Images in this article

Click on the image to see a larger version.

11/03/16 16:32PubMed Central, Table 2: Arthrosc Tech. 2012 Sep; 1(1): e63–e68. Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003

Page 1 of 1http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678655/table/tbl2/

PMC full text: Arthrosc Tech. 2012 Sep; 1(1): e63–e68.Published online 2012 Apr 21. doi: 10.1016/j.eats.2012.02.003Copyright/License ► Request permission to reuse

Table 2

Postoperative Rehabilitation After Arthroscopic Hip AMIC

1 d Postoperatively 2 d to <4 wk

Postoperatively

4 wk to <6 mo

Postoperatively

6 mo to <1 yr

Postoperatively

1 yr

Postoperatively

Load bearing None None Partial load bearingup to 7 wk;afterward, full

Full Full

Mobilization Continuous passivemotion at 60° of hipflexion

Regain step-wise fullrange of motion

No restriction No restriction No restriction

Physiotherapyand sport

No sporting activitiesIsotonic and isometricquadriceps exercises

No sporting activitiesActive and passivephysiotherapy

Light sportingactivities (e.g.,swimming andcycling)

Jogging Full return tosports

. Mínimamente invasivo, 1 procedimiento, tratamiento base estimulación subcondral, protección coágulo y ‘Cambra Bioactiva’, se reduce hospitalización y más rápida recuperación. Coste-Efectivo.

Page 15: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

PublicacionesLiterature1. Biant, L. C., Bentley, G., Vijayan, S., Skinner, J. A. & Carrington,

R. W. J. Long-term Results of Autologous Chondrocyte Implantation

in the Knee for Chronic Chondral and Osteochondral Defects. Am. J.

Sports Med. 42, 2178–83 (2014).

2. Knutsen, G. et al. Autologous chondrocyte implantation compa-

red with microfracture in the knee. A randomized trial. J. Bone Joint

Surg. Am. 86-A, 455–64 (2004).

3. Jäger, M., Feser, T., Denck, H. & Krauspe, R. Proliferation and os-

teogenic differentiation of mesenchymal stem cells cultured onto three

different polymers in vitro. Ann. Biomed. Eng. 33, 1319–32 (2005).

4. Gooding, C. R. et al. A prospective, randomised study comparing

two techniques of autologous chondrocyte implantation for osteo-

chondral defects in the knee: Periosteum covered versus type I/III col-

lagen covered. Knee 13, 203–10 (2006).

5. Chen, J. M., Willers, C., Xu, J., Wang, A. & Zheng, M.-H. Autolo-

gous tenocyte therapy using porcine-derived bioscaffolds for massive

rotator cuff defect in rabbits. Tissue Eng. 13, 1479–91 (2007).

6. Jäger, M. et al. Bone healing and migration of cord blood-derived

stem cells into a critical size femoral defect after xenotransplantation.

J. Bone Miner. Res. 22, 1224–33 (2007).

7. Iwasa, J., Engebretsen, L., Shima, Y. & Ochi, M. Clinical appli-

cation of scaffolds for cartilage tissue engineering. Knee Surg. Sports

Traumatol. Arthrosc. 17, 561–77 (2008).

8. Gomoll, A. H., Probst, C., Farr, J., Cole, B. J. & Minas, T. Use of

a type I/III bilayer collagen membrane decreases reoperation rates for

symptomatic hypertrophy after autologous chondrocyte implantation.

Am. J. Sports Med. 37 Suppl 1, 20S–23S (2009).

9. Brittberg, M. Cell carriers as the next generation of cell therapy for

cartilage repair: a review of the matrix-induced autologous chondrocy-

te implantation procedure. Am. J. Sports Med. 38, 1259–71 (2010).

10. Harris, J. D. et al. Failures, re-operations, and complications after

autologous chondrocyte implantation--a systematic review. Osteoarth-

ritis Cartilage 19, 779–91 (2011).

11. Saris, D. et al. Matrix-Applied Characterized Autologous Cultured

Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospec-

tive Randomized Trial. Am. J. Sports Med. 42, 1384–1394 (2014).

12. Brittberg, M., Price, A., Yu, Q., Kili, S. & Saris, D. Poster: SUMMIT

Trial : Matrix-induced Autologous Chondrocyte Implant versus Microf-

racture at 3 Years. in Poster AAOS Annu. Meet. 2015, Las Vegas,

Nevada (2015).

13. Dhollander, A. A. M. et al. Autologous matrix-induced chondroge-

nesis combined with platelet-rich plasma gel: technical description and

a five pilot patients report. Knee Surg. Sports Traumatol. Arthrosc. 19,

536–42 (2010).

14. Gille, J. et al. Cell-Laden and Cell-Free Matrix-Induced Chondro-

genesis versus Microfracture for the Treatment of Articular Cartilage

Defects: A Histological and Biomechanical Study in Sheep. Cartilage 1,

29–42 (2010).

15. Gille, J. et al. Mid-term results of Autologous Matrix-Induced

Chondrogenesis for treatment of focal cartilage defects in the knee.

Knee Surg. Sports Traumatol. Arthrosc. 18, 1456–64 (2010).

16. Anders, S., Volz, M., Frick, H. & Gellissen, J. A Randomized, Con-

trolled Trial Comparing Autologous Matrix-Induced Chondrogenesis

(AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of

2 Centers. Open Orthop. J. 7, 133–43 (2013).

17. Gille, J. et al. Outcome of Autologous Matrix Induced Chondroge-

nesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch.

Orthop. Trauma Surg. 133, 87–93 (2013).

18. Bark, S. et al. Enhanced microfracture techniques in cartilage

knee surgery: Fact or fiction? World J. Orthop. 5, 444–9 (2014).

19. Lee, Y. H. D., Suzer, F. & Thermann, H. Autologous Matrix-In-

duced Chondrogenesis in the Knee: A Review. Cartilage 5, 145–153

(2014).

20. Benthien, J. P. & Behrens, P. Nanofractured autologous matrixin-

duced chondrogenesis (NAMIC©) — Further development of collagen

membrane aided chondrogenesis combined with subchondral need-

ling. Knee (2015). doi:10.1016/j.knee.2015.06.010

21. Benthien, J. P. & Behrens, P. Reviewing subchondral cartilage

surgery: considerations for standardised and outcome predictable car-

tilage remodelling: a technical note. Int. Orthop. 37, 2139–45 (2013).

22. Behrens, P., Varoga, D., Niemeyer, P. & Salzmann, G. Intraopera-

tive biologische Augmentation am Knorpel. Arthroskopie 26, 114–122

(2013).

23. Min, B.-H. et al. Effect of different bone marrow stimulation

techniques (BSTs) on MSCs mobilization. J. Orthop. Res. Off. Publ.

Orthop. Res. Soc. 31, 1814–1819 (2013).

24. Eldracher, M., Orth, P., Cucchiarini, M., Pape, D. & Madry, H.

Small Subchondral Drill Holes Improve Marrow Stimulation of Articular

Cartilage Defects. Am. J. Sports Med. 42, 2741–2750 (2014).

25. Benthien, J. P. & Behrens, P. The treatment of chondral and

osteochondral defects of the knee with autologous matrix-induced

chondrogenesis (AMIC): method description and recent developments.

Knee Surg. Sports Traumatol. Arthrosc. 19, 1316–9 (2011).

26. Piontek, T., Ciemniewska-Gorzela, K., Szulc, A., Naczk, J. &

Słomczykowski, M. All-arthroscopic AMIC procedure for repair of car-

tilage defects of the knee. Knee Surg. Sports Traumatol. Arthrosc. 20,

922–5 (2012).

27. Hunziker, E. B. & Stähli, A. Surgical suturing of articular cartilage

induces osteoarthritis-like changes. Osteoarthritis Cartilage 16, 1067–

73 (2008).

Page 16: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

CAR2530Aluminium Template

Descripción: Kit para reparación de lesiones focales de cartílago grado III / IV clasificación ICRS

Composición: Matriz estructurada de colágeno/elastina biodegradable CARTIMAIX

Aguja guía de precisión para nanofracturas de Nitinol/Acero inox. NANO FX

Distribuidor nacional: BIOTECHPROMED SL

Marca Comercial: CARTINAMIC

Fabricante: MATRICEL GmbH, Alemania / ARTRHOSURFACE, USA

Referencias: CARNR23

CARNR34

CARNR45

CARNT23

CARNT34

CARNT45

Descripción: Matriz estructurada de colágeno/elastina biodegradable y aguja guía nanofractura

Indicación: Lesiones focales de cartílago grado III/IV en rodilla, tobillo, cadera, hombro, codo o muñeca

Cartimaix Plantilla medición

Imagen de producto:

Nano FX

Matriz estructurada: Medidas embalaje: 21,6 x 11,9 x 3,0 cm. Peso: 75 gramos

Material/Composición:

Colágeno ( de origen porcino) CAS-No. 9007-34-5 // EC-No. 232-697-4

Elastina ( de origen porcino) CAS-No. 9007-58-3 // EC-No. 232-701-4 Concentración < 30% (W/W)

Aguja Guía:

Nitinol (Níquel-Titanio) de acuerdo con ASTM F 2063-05 (16,3mm Astrágalo/17,3 rodilla-hombro) y Acero Inoxidable (Punta 8mm astrágalo/9mm rodilla-hombro y cabezal 3,1mm). 5,67gr

Envasado: Doble embalaje, esterilizado mediante rayos gamma, libre de pyrogeno

Conservación y Almacenamiento: Almacenamiento en condiciones estándar de higiene sanitaria. Proteger de contaminación. Temperatura ambiente.

Seguridad: Producto no clasificado como peligroso ni tóxico según la Directiva 67/548/EEC y regulación (EC) No. 1272/2008

Garantía de calidad: CE 0481 / CE0459

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Ficha Técnica

Page 17: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

Conclusiones

cartinamic cartinamic Conclusiones

. NAMIC: Condrogénesis Autóloga Inducida por Nanofractura sobre una Matriz

. El coágulo con células madre autólogas provenientes de la médula ósea parece ser la base de la reparación de cartílago

. CARTINAMIC potencia el coágulo favoreciendo la migración de células madre autólogas provenientes de la médula ósea de forma mínimamente invasiva mediante la Nanofractura,, además de estructurarlo, protegerlo y facilitar el anclaje y proliferación celular mediante la matriz estructurada Cartimaix

. Cartimaix: Tecnología probada > 12 años de seguimiento

. Resistente, Estructurada, Biodegradable

. Publicaciones nivel 1 de evidencia

. Nano FX: Eficiencia en estimulación MIS de la médula subcondral

. Permite tratamiento lesiones condrales puras y osteocondrales con aporte óseo

. Permite combinar con otras técnicas (Células Madre, C. Condrocitos, PRP )

. Alta Coste-Efectividad. Precio vs otras técnicas

Page 18: cartinamic - Biotechpromed · Small subchondral drill holes of 1.0 mm seem to stimulate a better cartilage regeneration in the sheep model[15]. ... son necesarios para una regeneración

¿Cuál es el problema?

cartinamic cartinamic

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión.

. Lesions condral pura : recomendado técnica NAMIC

. Lesió osteocondral: recomendado ANAMIC. Augmented NAMIC Technique o técnica ‘Sandwich’ con aporte de hueso cresta ilíaca.

No esta indicado para pacientes artrósicos.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Varón 33a. Área lesión: 3.6cm2Reintervención Lesión Condral Rodilla

. El tratamiento no adecuado de estas lesiones, conduce a la artrosis y futura necesidad de prótesis en edades prontas

. Saris et al. publicaron (J.S.Med. 2008) 21.6 meses como tiempo de reoperación de los pacientes tratados mediante Microfractura

Mujer 18a. Área lesión: 2 cm2Lesión Condral Astrágalo

Varón 37a. Área lesión: 2.5 cm2Lesión Condral Acetábulo.

Lesiones de cartílago focales, aisladas, de grado 3 o 4 sintomáticas, de 2 cm2 a 6 cm2 de extensión. No esta indicado para pacientes artrósicos.

¿Cuál es el problema?

cartinamic cartinamic

W W W . C A R T I M A I X . C O M

C O L L A G E N M E M B R A N E

The membrane for safe

cartilageregeneration

BIOTECHPROMED, S.L.

c/ Osio, 53, 08034 Barcelona, EspañaC.I.F. nº B65914277

OFERTA KIT NANO FX

LA MEMBRANA PARA UNA REGENERACIÓN SEGURA DEL CARTÍLAGO

La membrana para una segura REGENERACIÓN DEL CARTÍLAGO

t: 0034673911207