Hybrid hydrogel system integrating thermoresponsive microspheres and KGN-loaded nanofibers enables efficient...

Articular cartilage has limited self-repair ability, and effective therapies for defects remain challenging. Injectable hydrogels are attractive for cartilage tissue engineering as they can fill irregular defects and mimic the native extracellular matrix (ECM). However, current hydrogels often suffer from dense microstructures, poor mechanical stability and inadequate biological signaling, restricting tissue regeneration. In this study, a multifunctional injectable hydrogel system based on oxidized dextran and carboxymethyl chitosan (ODex/CMCS) was developed by integrating degradable gelatin microspheres (GMs) and kartogenin-loaded cross-linked gelatin fibers (KGN@GFs). The GMs served as thermosensitive, dissolvable porogens that generated an interconnected porous structure within the hydrogels to enhance nutrient diffusion, cell infiltration and tissue ingrowth, while the KGN@GFs provided sustained KGN release and additional mechanical reinforcement. The resulting composite hydrogels exhibited favorable injectability, self-healing capability and a porous architecture conducive to cell survival and spatial organization. In vitro experiments demonstrated good cytocompatibility and significantly enhanced chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, implantation in rabbit cartilage defect models revealed that the ODex/CMCS/KGN@GFs/GMs hydrogel effectively promoted hyaline-like cartilage regeneration and integration with surrounding tissue. Collectively, this work presents a structurally and functionally optimized injectable hydrogel system that synergistically combines biochemical and structural cues to promote cartilage repair.