the role of regenerative medicine · • mscs or buffy coat seeded in a biological or artificial...
TRANSCRIPT
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Department of Orthopaedics
Polytechnic University of Marche
Ancona - Italy
A. Gigante
The role of Regenerative Medicine
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• Articular environment (patient – pathology – grade – side/size)
• Scaffolds
• Cells
TISSUE ENGINEERING
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• Biological environment (patient – pathology – grade – side/size)
• Scaffolds
• Cells
TISSUE ENGINEERING
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* Natural polymers
SCAFFOLDS FOR CARTILAGE
• Hydrogels (agarose - alginate) Wang et al., 2007
• Chitosans Muzzarelli et al., 1995
• Synthetic materials (PLA - PGA – PDS)
• Human cartilaginous matrix
• Hyaluronic acid* Pavesio et al., 2003
• Collagen types I and II* Gigante et al., 2003
• Collagen I* + Hydroxyapatite Roveri et al., 1998
• Polysaccharides* (CS photocrosslinkable) Li et al., 2004
• Fibrin gel* Homminga et al., 1993
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Biomimicry
BIOMATERIALS PROPERTIES
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CELLS SCAFFOLD
BIOMIMIC SCAFFOLDS
• Collagen I membranes for tendon repair: effect of collagen fiber orientation on cell behavior. Gigante A et al. J Orthop Res. 2009 Jun; 27(6):826-32.
• Adult mesenchymal stem cells for bone and cartilage engineering: effect of scaffold materials. Gigante A et al. Eur J Histochem. 2008; 52(3):169-74.
• Engineered articular cartilage: influence of the scaffold on cell phenotype and proliferation. Gigante A et al. J Mater Sci Mater Med. 2003 Aug;14(8):713-6.
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CARTILAGE EXTRACELLULAR MATRIX
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COLLAGEN
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• Chondrocytes in suspension covered by a
membrane (II generation);
• Chondrocytes grown on biological or artificial
scaffolds (MACI – III generation);
• Microfracture covered by a membrane
(AMIC);
• MSCs or buffy coat seeded in a biological or
artificial scaffolds.
SCAFFOLDS
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• invasiveness
(mini-open approach or
arthroscopic method)
• operative time
• patient discomfort
Chondrocytes – microfractures – MSCs
grown on biological or artificial scaffolds
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COLLAGEN AS SCAFFOLD
CELLS
CELLS FROM MICROFRACTURES
MESENCHIMAL STEM CELLS (buffy coat)
DIFFERENTIATED CHONDROCYTES
TWO STEPS
ONE STEPS
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MACI® & NOVOCART® 3D
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MACI type I, III collagen (porcine)
Safranin O S-100
protein
Cell density 106
mln/cm2
Gigante et al., 2006
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Not controlled, prospective study,
mono and multicentric data
Clinical experience
D’Anchise R., Manta N., Prospero E., Bevilacqua C., Gigante A.
Autologous implantation of chondrocytes on a solid collagen scaffold after two years of follow up.
J Orthopaed Traumatol 6: 36-43, 2005.
Cherubino P., Grassi F.A., Bulgheroni P., Ronga M.
Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report.
J Orthop Surg., 11(1): 10-5, 2003
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• 59 consecutive cases (10 ♂ - 5 ♀)
• Median age 31
• Follow up 3-5 years
• 51 isolated – 8 multiple lesions
• 33 trauma and microtrauma
• 9 OCD
• 8 degenerative
• 0 connective disease
Patients and methods
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Indications
Knee
2 cm2 – max 8 cm2 - mean 4 cm2
Ankle
1 cm2 – max 4 cm2 - mean 2 cm2
33 trauma and microtrauma - 9 OCD
8 degenerative – 0 connective disease
Patients and methods
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Associated treatment:
• 9 ACL reconstructions
• 7 valgus osteotomies
• 9 p.f. distal realignments
Patients and methods
Distal realignment and patellar ACI: mid term results in a
selected population.
Gigante A, Enea D, Greco F,
Bait C, Denti M, Schonhuber H, Volpi P
Knee Surg Sports Traum Arthr 2009 ; 17:2-10
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Isolated lesions
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Multiple lesions
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Degenerative lesions: “unshouldered lesions”
• MACI + tissucol + polar sutures
Patients and methods
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14 MACI:
Grading III-IV Outerbridge
Size > 2cm2
Causes:
» 7 malallineaments
» 5 trauma
» 2 doc
Patella and throclea
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Glued + sutured membrane Patella
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Glued + sutured membrane
Patella
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Patella: Glued + sutured membrane + TTT
Distal realignment and patellar ACI: mid term results in a selected population.
Gigante A, Enea D, Greco F, Bait C, Denti M, Schonhuber H, Volpi P
Knee Surg Sports Traum Arthr 2009 ; 17:2-10
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Knee: maci by arthroscopy
Arthroscopic Delivery of Matrix-Induced Autologous Chondrocyte Implantation:
International Experience and Technique Recommendations
F. Cortese, M. McNicholas, G. Janes, S. Gillogly, S.P. Abelow, A. Gigante, N. Coletti
Cartilage, 2011, in press
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6 ankle (talus) Gigante et al., JBJS, 2005
ANKLE Ankle: maci by arthroscopy
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• Subjective knee function state
VAS (1,2,3,6,12 and 24 M)
• Objective finding:
1. ICRS-surgeon form part
(1: normal; 2: nearly normal;
3: abnormal; 4: severely abnormal)
2. Lysholm and Tegner scores at
baseline and after 6, 12 and 24 months
Materials and methods
“Modified ICRS score”
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TIME
(MONTHS)
0 1 6 12 24 36
N PATIENT/
KNEE 5,42
±1,5
2,71
±1,4
1,03
±1,5
0,45
±0,8
0,21
±0,4
0,23
±0,4
VAS
FUNCTIONAL STATE
TIME
(MONTHS)
0 1 6 12 24 36
2.55±0.
51
* 1.12±0.
31
1.06±0.
27
1.00±0.
25
1.03±0.
25
00:00
01:12
02:24
03:36
04:48
06:00
preop. 6 months 24 months
VAS
Function
Clinical Results at 3 years
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IKDC SCORE (from ICRS score)
TIME (MONTHS) 0 6 12 24 36
Functional
test
3.23
±0.45
1.04
±0.39
1.28
±0.37
1.00
±0.25
1.00
±0.02
Ligament
examination
1.17
±0.34
1.05
±0.27
1.07
±0.28
1.06
±0.28
1.06
±0.58
Passive
motion Deficit
1.06
±0.29
1.03
±0.23
1.00
±0.25
1.00
±0.25
1.00
±0.36
Effusion/
compartment
s findings
2.25
±0.49
1.26
±0.36
1.16
±0.33
1.04
±0.27
1.04
±0.17
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Jamshidi needle mm. 3 Ø deep > 5 mm
2nd look and biopsy
• 12 - 24 months
• 22 cases fron multicentric national study
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2nd look and biopsy at 12 months
MACI at medial condyle and ACL reconstruction
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Feature/score 0 1 2 3
I. Surface Discontinuities/
irregularities
Smooth/
continuous
II. Matrix Fibrous tissue Fibrocartilage Misture:
hyaline/fibro
cartilage
Hyaline
III. Cell distribution Individual
cells/disorga
nized
Clusters Mixed/columnar-
clusters
Columnar
IV. Cell population
viability
<10% viable Partially viable Predominantly
viable
V. Subchondral Bone Detached/fractur
e/callus at
base
Bone
necrosis
Increased
remodelling
Normal
VI. Cartilage
mineralization
Abnormal/inappr
opriate
location
Normal
ICRS Visual Histological Assessment Scale
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Membrane completely reabsorbed at 12 months
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ICRS Visual Histological Assessment Scale
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Feature/score 0 1 2 3
V. Subchondral Bone Detached/fractu
re/callus at base
Bone
necrosis
Increased
remodelling
Normal
VI. Cartilage
mineralization
Abnormal/inappr
opriate location
Normal
ICRS Visual Histological Assessment Scale
19/22
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The histological data have confirmed that the regenerated cartilage is a typical hyaline cartilage, with a straight tide-mark with subchondral bone, well-organized cell-clusters and strong reactivity for hyaline markers.
MACI: conclusions
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The cost efficiency
of this technique
remains to be evaluated
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COLLAGEN AS SCAFFOLD
CELLS
CELLS FROM MICROFRACTURES
MESENCHIMAL STEM CELLS (buffy coat)
DIFFERENTIATED CHONDROCYTES
TWO STEPS
ONE STEPS
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Cells from buffy coat + collagen membrane
ONE STEP
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MERG
membrana per riparazione guidata
• autologous
• lower costs
• one step
• multi-potent?
ONE STEP
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Buffy coat (marrow cells) + Collagen scaffold (MERG)
7 biopsies > 1 year
Gigante A. and Calcagno S.
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MERG 7 biopsies > 1 year
Gigante A., Calcagno S., Cecconi S., Ramazzotti D., Manzotti S., Enea D.
Use of collagen scaffold and bone marow concentrate as a one step cartilage repair in the knee.
Int. J. Immunopathol. Pharmacol., 24 (suppl.2), 69-72, 2011
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• Articular environment (patient – pathology – grade – side/size)
• Scaffolds
• Cells
TISSUE ENGINEERING
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Thanks