Immunomodulatory and anabolic biphasic scaffold with hierarchical biomimetic structure directed osteochondral defect repair.

Repairing osteochondral tissue is challenging due to its hierarchical structure, mechanical heterogeneity, and the need for spatial control over stem cell differentiation. Advances in tissue engineering have facilitated the development of biphasic cartilage-bone integrated scaffolds for osteochondral repair. The cartilage layer, composed of an IGF-1-loaded polydopamine-ZIF8/HAMA hydrogel, mimicked native tissue and enabled controlled cytokine release. This layer promoted M2 macrophage polarization, enhanced BMSC migration and chondrogenesis, and improved cartilage anabolism. The subchondral bone layer was a nanoclay (XLS)-functionalized 3D bioglass scaffold, which provided superior mechanical strength and supported osteogenic differentiation. These layers were integrated via partial interpenetration of the HAMA hydrogel. Importantly, in vivo studies confirmed that our biphasic scaffold effectively promoted osteochondral defects regeneration in a rat lower femoral osteochondral defect model. Collectively, this biphasic scaffold system presents a promising therapeutic strategy for osteochondral tissue regeneration.