Injectable ECM hydrogel for delivery of BMSCs enabled full-thickness meniscus repair in an orthotopic rat model

Meniscal injuries have poor intrinsic healing capability and are associated with the development of osteoarthritis. Decellularized meniscus extracellular matrix (mECM) has been suggested to be efficacious for the repair of meniscus defect. However, main efforts to date have been focused on the concentration, crosslinking density and anatomical region dependence of the mECM hydrogels on regulation of proliferation and differentiation of adult mesenchymal stem cells (MSCs) in vitro 2D or 3D culture. A systematic investigation and understanding of the effect of mECM on encapsulated MSCs response and integrative meniscus repair by in vivo rat subcutaneous implantation and orthotopic meniscus injury model will be highly valuable to explore its potential for clinical translation. In this study, we investigated the in situ delivery of rat BMSCs in an injectable mECM hydrogel to a meniscal defect in a SD rat model. Decellularized mECM retained essential proteoglycans and collagens, and significantly upregulated expression of fibrochondrogenic markers by BMSCs versus collagen hydrogel alone in vitro 3D cell culture. When applied to an orthotopic model of meniscal injury in SD rat, mECM is superior than collagen I scaffold in reduction of osteophyte formation and prevention of joint space narrowing and osteoarthritis development as evidenced by histology and micro-CT analysis. Taken together, these results indicate mECM hydrogel is a highly promising carrier to deliver MSCs for long-term repair of meniscus tissue, while preventing the development of osteoarthritis.