A soft-hard hybrid scaffold for osteochondral regeneration through integration of composite hydrogel and biodegradable magnesium

Osteochondral injuries are prevalent and difficult to treat in clinical practice. Traditional tissue engineering typically results in poor integration at the calcified cartilage interlayer, since they cannot address different needs from the cartilage and the supporting subchondral bone. This study presents a hybrid biological scaffold integrating soft and hard components to systematically adopt to osteochondral regeneration. The upper section consists of bioactive hydrogel, kartogenin (KGN), and bone marrow stromal cells (BMSCs), replicating mechanical properties and chondrogenic potential of nature hyaline cartilage. The lower section utilizes a biodegradable metal magnesium (Mg) alloy scaffold with customized porous structure, providing mechanical response comparable to trabecular bone, along with regulated degradation and enhanced angiogenesis and osteogenesis. The bioactive hydrogel is compressed into the pores of Mg scaffold. Notably, the unique combination not only significantly improves mechanical response and fatigue resistance of the cartilage section but also maintains interface stability throughout the repair process. Accordingly, the hybrid scaffold effectively promotes the regeneration of both cartilage and subchondral bone simultaneously by upregulation of osteogenic and chondrogenic specific genes. Overall, this work provides valuable insights for treating osteochondral injuries by material–structure–function integrated strategies.