Ph ADAM, MDSports Clinic

Medipole Garonne Toulouse France

Use of PRP-HA (Cellular MatrixTM) for the Treatment of Articular

and Peri-Articular DiseasesBy UltraSonographic Guidance

11ème congrès de la Société Marocaine

d’Arthroscopie03-04 Février 2017 à

Marrakech

CMTM is the « All-in-one » Therapeutic Injection with a mix of PRP-HA

1/Into the Articular Cavities (Knee and Other Joints) :*US Synovial Cavity approach (Arthritis) to detect an

effusion (arthrocentesis for a dry joint+++ before CMTM)

*US Meniscal approach (or other fibro-cartilages)

2/and Outside of the Joints :Direct US access to Synovial Sheaths of Tendons

and Synovial Bursae

Medipole Garonne (8/2012 till 9/2016) : 1562 PRP-HA procedures

PRP-HA

1/Association PRP-HA (Cellular MatrixTM Regen Lab®) is nor a Placebo neither a Visco-Supplementation

improved by PRP !

2/PRP (GF) produce antalgic and anti-inflammatory effect increase collagen synthesis and endogenous HA production

3/PRP-HA (CMTM) is more efficient than PRP onlyby synergistic anabolic actions of HA and PRP

•L’effet « Visco » n’est pas celui recherché

•C’est essentiellement l’effet biologique qui nous intéresse

•La préparation de PRP en présence d’HA, permet de former un réseau biologique dans lequel les plaquettes sont dispersées

•La fibrine interagit avec l’HA et forme un réseau à grandes mailles

•Ce réseau est propice à la migration et à la division cellulaire »

Why the association of Growth Factors (« PRP » « PRGF ») and HA ?

Microvasc Res. 2007 Mar;73(2):84-94. Epub 2007 Jan 16. Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules.

SMITH JD et al

Our Protocol for PRP-HA is codified but simple

1/Medical Consultation before : scores (IKDC, Oxford, Womac…), imaging modality (US,CT,MR), consent of patient, blood count, premedication (antalgic, patch) and stop anticoagulant drugs

2/PRP-HA is a very short procedure (≈20 mn) with blood sample, centrifugation

and injection in the UltraSonographic room with Meopa inhalation if necessary

3/Clinical and Imaging control after at 5 weeks (US or MRI) + sports resumption in coordination with sportive medical team

4/Number of injections is from 1 to 3 according to the indication

with several months between each injection, but If first injection is highly effective one can wait one year of interval

I/Grade II (closed) and III (open) stable degenerative (or traumatic) meniscal tears

+ “Big” painful meniscus (para and intra-meniscal cyst)

A stable knee is needed for a good result of medical treatmentby PRP injection for healing of meniscal tears+++ (collagen effect)

Stable kneeUnstable

kneeACL torn

*Peripheral Vascularity seem to play an important role in meniscal healingbut deep meniscus is also soaking into the joint fluid !

*Therefore growth factors can impact meniscal healing by stimulation of vascular proliferation (meniscal wall+++) and by impregnation (joint)

Images of Meniscal anatomy

by cortesy of Mikel Sanchez

R R R W WW

Knee Joint : UltraSonographic approach

Before injection

After PRP

injection

perimeniscal

Sub-patellar

Perimeniscal needle

US control

1/ We need a direct injection of PRP-HA the closest possible to the meniscal lesion and to cartilage

(peripheral cleft/cyst/big bulging meniscus, early arthritis)

2/ Our purpose is to reduce meniscal tear both by the vascular side (wall, RR and RW areas)

and by the articular side (grade III open tear, WW area)

Needle into the bulging meniscusthrough the meniscal wall

3 cases of UltraSonographic Meniscal Wall Infiltration

1/Meniscal wall Medial meniscus

2/Meniscal wall Lateral meniscus

3/Lateral Meniscal Cyst : drilling then evacuation of the cystby « meniscal wall » way and PRP injection (CMTM)

Grade III meniscal tear and cyst Initial big functional disability, pain 8/10, woman 23 yo

Intra and extra meniscal cyst are decreasing, wall edema also (hypersignal decrease) : stabilization of the meniscal tear after CMTM

Meniscal wall lesion is the area with increased (white) signal (MRI)

3 months after CMTM walk normally, pain 0/10

Grade III

Grade II peripheral meniscal tear before PRP treatment

MRI : Grade II meniscal tear has almost disappeared after treatment

Bulging Meniscus (posterior horn)

Dancer woman 33 YO Postero-medial pain of knee without traumaUltrasonography : bulging medial meniscus (not extruded)

First MRI 2016 March : cystic degenerative medial meniscus (« big white »)

Flat MeniscusSecond MRI 2016 April *One month after PRP-HA

Cystic appearance decrease (partial collapse) and painDance again with high-heeled shoes

1

1

2

2

May be a new US entity for the US-guided treatment ? The « big bulging round meniscus » (nor discoid neither extruded)

This Bulging Meniscus is not* a degenerative meniscus ejected outside the joint as in the OA but* a big degenerative meniscus

with a painful para-articular mass

2/For grade II and III degenerative meniscal tears there was a significant improvement in the IKDC subjective score one year after

the beginning of PRP-HA treatment, with a mean score of 7,96 (range 5 to 10/10) compared to 4.20 (range 0 to 6/10) before

3/A follow-up study at 2 years in August 2015 found 52% of subjects with a long-term improvement after only one injection

First Meniscal Study in Medipole GaronneEfficiency of PRP-HA

1/From August 2012 to June 2013, 93 patients (aged between 23 and 84 years, mean age 49, gender ratio: 24% females vs 75% males) suffering from Grade II or III (80% grade III) stable horizontal lesion (85% medial meniscus, 15% lateral meniscus, RR or RW meniscal area) were treated with only one i-a injection of CMTM

II/Kellgren and Lawrence (X-Ray) Moderate Grade II and Grade III Knee Osteo-Arthritis

Meniscal extrusion demonstated by US

is a sign for evolutive arthritis by rupture of perimeniscal

fixations

Davies-Tuck et al stated that « the development of new BMLs was associated with progressive knee cartilage pathology, while resolution of BMLs prevalent at baseline was associated with reduced progression of cartilage pathology »

(Arthritis Res Ther. 2010;12(1):R10, page 7)

US guidance for injection

MRI for post-PRP control (BME bio-marker)

2/The Early Detection and Early Treatment of BML/BME allows a good Prevention of OA and can delay the prosthetic stage

1/The Correlation between Bone Marrow Lesions (BML) Bone Marrow Edema (BME), Pain and Loss of Cartilage (OA)

PRP-HA for the treatment of OA is justified by

3/The Study of Sanchez which demonstrated the superiority of PRP versus Hyaluronic Acid for knee OA

Sanchez M, Anitua E, Azofra J, Aguirre JJ, Andia I. Intraarticular injection of an autologous preparation rich in growth factors for the treatment of knee OA : a retrospective cohort study.

Clin Exp Rheumatol. 2008;26:910–913

*From September 2013 to April 2014, 71 patients (34 females and 37 males, 40 and 84/mean age 63, mean BMI 26.83), KL II (33 patients) and KL III (38 patients)

*Failure to Classical Visco-Supplementation

*3 Injections by patellar way (US) with CMTM were done at Day 0, Month 2 and Month 6 and evaluated at these three time-points by the Womac scale and at a final follow-up at Month 9

Multicenter Trial of Cellular Matrix for the treatment of Knee OA (20 patients from Medipole Garonne included)

WOMAC Pain at Day 0, Month 2, Month 6 & Month 9(Multicenter Trial)

Pain was gradually decreasing after each injectionPRP-HA is effective when Classical Visco-Supplementation failed

Now, in November 2016, approximately 3 years after the OA study in Medipole Garonne, we reviewed in consultation half of patients (no news of the other half) with a satisfactory functionality, and no prosthetic device. These patients asked us a new injection. So we can confirm the durability of efficiency with CMTM intra-articular injection in comparison with a simple visco-supplementation (6 months in literature)

Woman 40 yo, overweight, KL III, internal pain 4/10 MRI at one month, pain 0/10

Obvious decrease of the hypersignal of medial femoral condyle (BME)

Other KL III, important decrease of BME and pain at one month after CMTM

III/Post-Traumatic OA (“osteo-chondritis”) with focal loss of superficial cartilage and

Bone Marrow Edema

Knee PTOA with BME of medial femoral condyle and superficial cartilage defect

(osteochondritis). Frontal plane (top) and axial plane (bottom) with a target signEdema and Pain highly decreased after US-guided PRP-HA at one month.

1/The BME Pattern is a non-specific finding

which could be found out of Traumatic Bone Bruise

and out of Osteo-Arthritis

2/We are using the « Anticatabolic Effect » of PRP-HA against BME

and algodystrophy

IV/Bone Marrow Lesions with Bone Marrow EdemaAlgoneurodystrophy Osteonecrosis and Stress FracturesUS guided sub patellar injection but MRI control of Edema

Knee Algoneurodystrophy after ligamentoplasty (before CMTM) : pain 6/10, lateral femoral condyle BME, small medial meniscal tear

Knee Algoneurodystrophy 5 weeks after CMTM : pain 1/10, BME 0, articular collection

Neer’s Test with PRP

CTX RayUS Target

V/ PRP-HA (CMTM) for Sub-acromial ConflictTendon Sheaths and Bursae

UltraSonographicGuidance+++

US guided PRP-HA (CMTM)1/Acromio-clavicular way

(needle tract)

Neer’s Test with CMTM for Sub-acromial Conflict (impigement syndrome)

US guided PRP-HA2/Sub-acromial way (needle tract)

Sub-acromial Conflict

and supra-spinatus tendon tear

Diffusion of PRP (hyperechogenic) into the

tendon tear and into subdeltoid bursa

Tendon Sheath : Tibialis Posterior Tendonitis with fluid collection

Before injection of US-guided PRP-HA

After injection of PRP-HA No fluid collection

Hip Bursitis : US-guided PRP-HAbetween Medius Gluteus Tendon and Trochanter major

Indications of PRP-HA for all the joints : Super PRP !

1/US guided PRP-HA can complete or replace classical VS :

*Limited action of HA alone (5 months)*PRP-HA 12 to 24 months

*HA is sometimes injected outside of the jointwithout US control (shoulder, forefoot, wrist, pubic joint…)

2/PRP-HA is better than for diabetic patients+++

3/PRP-HA is a good complement to surgery Post-operative recovery is better after PRP-HA (healing,

natural antalgic and anti-inflammatory effects, bacteriostatic)

4/Better results for the Knee then Hip and other

*Determining the best frequency for administering PRP-HA in the preventive treatment of OA is still unresolved !

*The purpose is to maintain a good clinical result for pain beyond one year and to delete surgical planning!

One PRP-HA injection each year for sportsmenor a course of one PRP-HA every two months

or 3 to 5 iterative i-a injections ?

*PRP-HA has the potential to reduce pain more effectively than Classical Visco-Supplementation, and to prevent or at least to slow the progression of meniscal lesions and OA

Conclusions (1)

*Protection of fibro-cartilaginous structures is clearly coupled with the protection of articular cartilage*We cannot ignore the fact that being overweight, or having traumatic instability or distortions of the skeleton disadvantages the therapeutic benefits of any treatment*Preventive treatment is extremely important regarding pain, functional limitation and cost of public health

Conclusions (2)

Early Screening(bio-markers+++, MRI)

+ Early Treatment

= Prevention and Efficiency

PRP-HA is a good complement to surgery

An association of techniques (HA + PRP + MSCs) will be more successful

than a single isolated technique if we want to make of a real cartilage

and not only a fibro-cartilage