Long-term durable repaired cartilage induced by SOX9 in situ with bone marrow-derived mesenchymal stem cells

Background: Microfracture is a common procedure for cartilage repair, but it often produces inferior fibrocartilage.We previously reported that a super positively charged SOX9 (scSOX9) promoted hyaline-like cartilage regeneration by inducing bone marrow derived mesenchymal stem cell differentiation into chondrocytes in vivo.Here we examined the long-term efficacy of cartilage repair induced by microfracture with scSOX9 by assessing the biomechanical property of the repaired cartilage.Methods: A cartilage defect was created at the right femoral trochlear groove in New Zealand female rabbits and microfracture was performed.The scSOX9 protein was administered at the site of microfracture incorporated in a collagen membrane.Results: At 12 and 24 weeks, scSOX9 treatment induced hyaline-like cartilage while collagen-membrane alone induced fibrocartilage and mutant scSOX9-A76E poorly induced cartilage repair.The cartilage matrix in scSOX9-treated group showed highly enriched proteoglycan content.Consistent with the histological feature and the thickness of the repaired cartilage, the mechanical property of scSOX9-induced cartilage was also similar to that of normal cartilage.Conclusion: This long-term in vivo study demonstrated that in combination with microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage which was durable in long-term.This technology has the potential to translate into clinical use for cartilage repair to prevent progression to osteoarthritis.