Injectable visible light cross-linking aldehyde-based methacrylated hyaluronic acid hydrogels enhance cartilage repair via improved BMSC homing and chondrogenic differentiation

Self-repair of articular cartilage defects is a significant challenge that can be addressed using drug-infused hydrogels, which improve injection convenience and provide immediate in situ adhesion. In this study, we developed a hydrogel incorporating Lipo@Kartogenin (KGN) and the cationic functional peptide SKPPGTSS (SKP) linked to aldehyde-based methacrylated hyaluronic acid (AHAMA). The innovative injectable hydrogel responded to visible light, allowing cross-linking under white light (~30 s) and effective adhesion to cartilage tissue. The hydrogel facilitated the sustained release of KGN and SKP over approximately 28 days as it degraded, thereby promoting the homing and differentiation of endogenous bone marrow-derived mesenchymal stem cells (BMSCs). Transcriptome sequencing showed that Smad4 expression and activation of the TGF-β signaling pathway are fundamental to these processes. In vivo studies in Sprague-Dawley (SD) rats showed that this hydrogel supports optimal hyaline cartilage regeneration within 8 weeks. In conclusion, our visible light-responsive adhesive co-delivery hydrogel effectively recruited native BMSCs to cartilage lesion sites and provided an environment conducive to their differentiation into cartilage, thereby facilitating effective cartilage regeneration. This innovation represents a novel approach to the clinical repair of cartilage defects.