Senior Director of Research and Operations The Stone Research Foundation, United States
Abstract: Articular cartilage damage significantly contributes to joint pain and leads to osteoarthritis (OA) if untreated. The Articular Cartilage Paste Graft technique repairs cartilage damage through autologous grafting of healthy bone and cartilage harvested from the intercondylar notch of the knee. Morselization of the damaged cartilage allows for infiltration of endogenous bone marrow stem cells resulting in de novo cartilage formation. Regeneration of normal hyaline cartilage is observed in one-third of patients; however, this technique lacks consistent defect fill and attachment of naive cartilage to neighboring tissue. We hypothesized that adding allogeneic human mesenchymal stromal cells (hMSCs) would amplify the effects of endogenous bone marrow stem cells and the addition of synthetic PEG hydrogel to the paste graft would serve as a scaffold to improve integration of regenerated tissue. In vitro, addition of hMSCs to human cartilage-hydrogel constructs increased GAG content significantly. Our in vivo rabbit model bolstered these findings, demonstrating the addition of MSCs and hydrogel to the paste graft resulted in almost full defect fill and significantly increased attachment to surrounding native tissue. Both histological analysis and confirmatory microCT imaging showed this combination of hMSCs, hydrogel, and autogenous paste treatment to consistently produce a robust repair of tissue architecture that integrated with endogenous tissue. Our novel paste graft construct harnesses the capacity of hMSCs to extensively regenerate and repair cartilage with the potential to prevent the onset of post-traumatic and degenerative OA. We are now advancing this approach into large animal trials under FDA and CVM guidance, with the future aim of significantly reducing the burden of cartilage injury and OA.
Funding Source: California Institute of Regenerative Medicine (DISC2-13131)
