Gellan gum/alginate-based Ca-enriched acellular bilayer hydrogel with robust interface bonding for effective osteochondral repair

The treatment of osteochondral (OC) defects remains challenging because of the lack of economical and feasible therapeutic strategies for OC repair and reconstruction. In this study, we report an integrated bilayer hydrogel with robust interface binding force (40 kPa) by facilitating the diffusion of calcium ions to the secondary crosslink of the bilayer hydrogel, in which gellan gum and sodium alginate acted as the chondral layer, gellan gum and hydroxyapatite acted as subchondral layer. This integrated construct has high cytocompatibility, and can seed with mesenchymal stem cells (MSCs) related to different functional protein expression for cartilage and bone formation, respectively. Furthermore, in the rabbit critical-sized osteochondral defect model (4.0 mm in diameter and 8.0 mm in depth), the calcium enriched hydrogel act as a calcium reservoir, promote neovascularization at week 4, and repair the critical defect at week 8, demonstrating the feasible preparation of an acellular hydrogel for OC repair.