Cartilage Repair Center
Disclosures
I have the following potential conflicts of interest: Consulting payments/royalties and research support:
- Vericel, Aesculap, Cartiheal, Regentis, JRF, SBM, NuTech, S&N, Exactech
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Cartilage Repair Center Brigham and Women’s Hospital
Harvard Medical School
Update on Clinical Studies Andreas H. Gomoll, MD
Associate Professor of Orthopaedic Surgery
Cartilage Repair Center
• I’m sorry!
– If I didn’t quote your study
– If I quoted a study from “that guy…”
– If I didn’t quote enough studies in your field
– If I quoted too many studies outside your field
– If I bored you with detail
– If I didn’t give you enough detail
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State of cartilage research
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Methodology
• Recent clinical publications on cartilage repair
• Studies that presented something new or
controversial
• Not an exhaustive review
• Food for thought
• Invitation to dig in on your own
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• Focus on clinical studies in cartilage repair
– Bone marrow stimulation
– “Microfracture plus”
– Autologous cell based therapy
– Osteochondral autograft
– Osteochondral allograft
– Scaffolds
– PRP
– Stem cells
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• Bone marrow stimulation
– Abrasion arthroplasty
– Microfracture
– Subchondral drilling
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• Bert J – Arthroscopy (2015)
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• Scilla et al. – AJSM (2015)
• 52 NFL players with arthroscopic chondroplasty
• 67% returned to play at 8.2 post-op, average FU 5.9 years
• No correlation with age, lesion size or location, position played or draft round
• Players who also underwent MFX were 4.4x less likely to RTP
• Less is more for professional athletes
• No procedure is a home run, including MFx
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• “Microfracture plus”
– Concerns over tissue quality with regular MFx
– Augment to bone marrow stimulation
• Mechanically stabilize clot
• Provide more favorable environment for cell differentiation
• Can be solid scaffold or paste
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• Micronized cartilage ECM as an additive to MFx
• 5 horses
• Internal (contralateral knee) control of regular MFx
• Better histology with augmented MFx
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• Technique: BST-CarGel® plus MFX VS MFX alone
• Study design: RCT
• Population: n: BST-CarGel®(n = 34) VS (n = 26)MFX,
• Outcomes: WOMAC, SF-36, MOCART. FU: 1y.
• Results:
– MRI analysis: BST-CarGel greater treatment effect for lesion
filling (P = 0.017) and T2 relaxation times
– Overall Clinical improvement, no difference between groups
• Mounting evidence that augments improve tissue quality above simple
MFx. Clinical benefit remains to be determined
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• Autologous cell-based therapy
– Chondrocytes
– Cultured or from cartilage fragments
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• Technique: Autologous bone graft + autologous cartilage chips
• Study design: case series
• Population: n: 8, OCD lesion in the knee, lesion size 3.1cm2, depth 8.4
mm, age 32.
• Outcomes: IKDC, KOOS, Tegner, MOCART. FU: 1y.
• Results:
– Overall Clinical improvement
• Very interesting development given financial and regulatory reality,
limiting access to cultured cells and allografts
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• Technique: RCT ACI vs microfracture
• Population: multicenter, n: 40 ACI vs 40 MFX, FU=15 years.
• Outcomes: Lysholm, Tegner, VAS.
• Results:
– no significant differences between the treatment groups.
– Failure rate 42.5% ACI and 32.5% MFx (p=0.356)
– 4 in each group revised with TKR, and additional 4 each with HTO
– One center with 60% failure rate for ACI
– K-L 2+: 57% ACI and 48% MFx (p>0.05)
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• Peterson (AJSM 2010):
• 224 patients average 12.8 years post-op ACI
• 92% satisfaction and would do ACI again
• Minas (CORR 2014):
• 210 patients average 12 years post-op ACI
• 25% failure rate, Better survival with concomitant HTO
• Biant (AJSM 2014)
• 104 patients, minimum 10 years post-op ACI
• 26% failure rate, 98% would do it again
• Claes (KSSTA 2013):
• OA after ACL: 50% in patients with meniscus injury
• High failure rate compared with other long-term studies
• No attention to alignment, meniscal status
• High rate of OA but comparable to ACL
• Avoiding OA is the holy grail, definitely not there yet
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• Technique: Case series ACI (synthetic type I/III collagen membrane)
• Population: Patients younger than 18 years, FU=4.6years, mean age
16.7. mean lesion size of 4.0 cm2.
• Outcomes: IKDC, (KOOS-QOL), Short Form–12 (SF-12) and other
KOOS subscores.
• High reoperation rate (37.8%) and limitations in knee function even after
ACI (IKDC 64, KOOS sports 61,
• Good pain relief (KOOS pain 78)
• Important message for patients. Even in an ideal population (young,
healthy, thin), repair of larger defects does not provide a perfect knee. If
that is the goal/promise, then patients will be unhappy
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• Technique: Cohort ACI (injected vs seeded collagen membrane)
• Population: 84 patients younger than 18 years, FU=4.6years, mean age
16.7. mean lesion size of 4.0 cm2.
• Outcomes: IKDC, KOOS, MOCART.
• Seeded ACI has same outcomes, possibly lower failure rate, easier
technique, than traditional injection under patch.
• One step closer to less invasive ACI
Gomoll et al. – accepted AJSM 2016
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• Osteochondral allograft transplantation
– Regulatory restrictions and supply issues limit
availability
– Expanded storage times to preserve chondrocyte
viability
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• 16 dogs implanted with OCA preserved for 28 or 60 days after harvest
• Investigated new storage medium
• Chondrocyte viability at time of implantation 23-99%
• All successful grafts had >70% viability
• No graft with <70% viability was successful
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• 32 patients treated with preserved de-cellularized osteochondral allograft
• 72% failure rate, average follow-up 1.3 years
• 43% revision rate
• 19.6% survivorship at 2 years
• Need viable chondrocytes for even short-term survival of OCA graft
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• Technique: match-paired cohort: primary OCA (group 1) VS OCA after failure
of previous MFX (group 2). 46 patients in each group
– Previous MFX didn’t affect the survivorship and clinical outcomes.
– Survivorship 87.4% and 86% in groups 1 and 2 at 10 years.
– 87% and 97% in groups 1 and 2 were ‘‘satisfied’’ or ‘‘extremely satisfied”
• ACI after Microfracture with worse results. Criticized for pre-selection bias.
MFx group had failed a procedure before -> knee loser, nothing to do with
microfracture itself.
• Effect disappears once you remove altered subchondral bone
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• Technique: case series, OCA transplant limited to the femoral trochlea.
• Population: 29 knees in 28 patients (mean age, 30.2 years), size: 6.1
cm2. Mean FU: 7 years
– Overall survivorship:
• 100% at 5 years
• 91.7% at 10 years
– Satisfaction
• extremely satisfied (63%), very satisfied (26%)
• Excellent outcomes of OCA in trochlea. Have healthy respect for the
technical challenges due to the complex geometry
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• PRP and Stem Cells
– Fastest growing area in cartilage repair/OA
treatment research
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• Technique: RCT, double-blind, PRP Smart-PReP®2 system (Harvest
Autologous Hemobiologics, Norwell, MA) vs Hyaluronic acid (2 mL of
Hylan G-F 20, Synvisc ; Biomatrix, Inc, Ridgefield, NJ)
• Population: n: 24 PRP vs 34 HA, patients treated for talar chondral
lesion with arthroscopic debridement and microfracture
• Both PRP and HA injections improved outcomes.
• Mechanical and biological components to pain
• We have been carpenters for too long, need to become gardeners (Bill
Bugbee).
• PRP is not like PRP, just like HA is not like HA
• Will take a lot of work to determine “the best” composition for each
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• Technique: Cohort 1-stage technique of HA scaffold and BMAC vs MFx
• Population: n: 25 (HA-BMAC) vs 25 MFX, Patients were placed into the
HA-BMAC vs MFx groups based on health insurance coverage of BMAC
– Tegner, IKDC objective, and (KOOS) higher in HA-BMAC
– Lysholm and IKDC subjective: similar
– Worse outcomes in MFX for lesions >4 cm2 and multiple lesions
• Recognition that MFx damages subchondral bone
• BMAC allows higher MSC numbers without violating plate
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Summary
Surgical Options 2006 – Microfracture
– Osteochondral Autograft
– Osteochondral Allograft
– Autologous Chondrocyte Implantation
Cartilage Repair Center
Summary
Surgical Options 2016 – Microfracture
– Microfracture Plus
– Osteochondral Autograft
– Osteochondral Allograft
– Preserved Osteochondral Allograft
– Particulated Juvenile Allograft Cartilage
– Perforated Cryopreserved Allograft Cartilage
– Autologous Chondrocyte Implantation
– Stem Cells
Cartilage Repair Center
Summary • Many new techniques show structural benefits
• Challenge will be to demonstrate clinical benefits
• Critically evaluate new implants before widespread adoption
• Increased cost consciousness of health systems
• Difficulty for expanded autologous tissue grafts
• Cell-free scaffolds promising but still need to prove themselves
• Osteochondral allograft use has shown excellent results
• Access to allograft tissue remains limited
• Lot of work remains – our jobs are safe…
• Treatment of OA is both biggest challenge and potential
• Start thinking more biological, less mechanical