HAMA-SBMA hydrogel with anti-inflammatory properties delivers cartilage organoids, boosting cartilage regeneration.

Cartilage tissue lacks blood supply, which limits its ability to self-repair. Cartilage organoid (CO) technology, which replicates the structure and function of cartilage, holds significant promise. However, it is essential to maintain cellular function and ensure secure fixation at the site of injury. Therefore, we loaded allogeneic bone marrow mesenchymal stem cells (BMSCs) onto decellularized extracellular matrix microparticles of porcine articular cartilage (CEP) to construct CO-CCO, which demonstrated characteristics of articular cartilage. Additionally, betaine sulfonate methacrylate (SBMA) was incorporated into hyaluronic acid methacrylate (HAMA) to synthesize a novel hydrogel, HAMA-SBMA (HS), characterized by its adhesive properties, promotion of chondrogenesis, and inhibition of inflammation. In Vivo studies revealed that the combination of HS and CCO (HS + CCO) exhibited excellent repair efficacy in both rat and sheep models of cartilage defects. Mechanistically, we found that HS + CCO promoted cartilage repair by activating the Frizzled-related protein (Frzb), which inhibited inflammatory factors and enhanced the expression of the adhesion factor integrin ɑ5β1. This strategy, which combines hydrogels and organoids, enhances cartilage repair, offering substantial potential for clinical applications in cartilage regeneration.