An engineered triple-network alginate/gelatin hydrogel mediates osteochondral regeneration through temporal...

Osteochondral defects (OCDs) present a significant clinical challenge due to the limited self-repair capacity of cartilage. Although platelet-rich plasma (PRP) holds therapeutic potential, its efficacy is limited by the rapid release of growth factors (GFs). In this study, we developed an injectable triple-network hydrogel, PRP@OSA-GEL, composed of oxidized sodium alginate (OSA), gelatin, and PRP. Crosslinked via dynamic Schiff base bonds, a fibrin network, and Ca²⁺-mediated ionic interactions, the hydrogel exhibits robust mechanical properties, self-healing, injectability, and sustained factor release. In vitro, it enhanced chondrocyte migration, matrix synthesis, and chondrogenic differentiation of BMSCs by temporally modulating the PI3K-AKT pathway. In a rabbit OCD model, implantation significantly improved hyaline cartilage and subchondral bone regeneration, with seamless integration. Furthermore, the hydrogel helped maintain cartilage homeostasis in human cartilage explants. These results indicate that PRP@OSA-GEL is a promising biomaterial for OCD repair, providing a clinically viable approach for sustained regenerative therapy.