A light-cured injectable composite hydrogel based on chitosan and decellularized matrix modulates stem cell aggregation behavior for accelerating cartilage defect repair

Cartilage repair remains a formidable challenge because of its limited regenerative capacity. Construction of a biomimetic hydrogel matrix that can induce cell aggregation is a promising therapeutic option. Cell aggregates are more beneficial than dissociated cells for improving survival and chondrogenic differentiation, thereby facilitating cartilage repair. Herein, we report a light-cured injectable composite hydrogel with cellular aggregation properties for cartilage defect repair that combines methacrylated chitosan (CSMA) and a methacrylate-modified decellularized extracellular matrix (dECMMA). The CSMA promotes cell aggregate formation by enhancing cadherin expression. The dECMMA retains many inherent components and bioactive factors, thereby providing a more natural microenvironment for cell proliferation and differentiation. By precisely adjusting the compositions of the CSMA and dECMMA, it was possible to fine-tune their physicochemical properties and biochemical cues. The results showed that a composite hydrogel composed of 2 % (m/v) CSMA and 5 % (m/v) dECMMA exhibited good injectability, appropriate degradability and mechanical properties, and regulated the formation of bone marrow mesenchymal stem cell aggregates. Transplantation of the composite hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) into a cartilage defect model demonstrated effective hyaline cartilage repair. Thus, light-cured injectable composite hydrogels embedded with BMSCs holds clinical promise for cartilage defect repair.