Osteochondral tissue regeneration faces persistent hurdles due to its complex composition and gradient physiological structure. Timely mechanical support during the formation of new cartilage is critical for achieving osteochondral defect reconstruction. Therefore, there is a need for biomimetic scaffolds that promoting structural integrity and functional recovery of osteochondral defects. Inspired by the inherent components and physiological structures of the natural osteochondral extracellular matrix (ECM), we presented a printable ink composed of natural polysaccharides (bacterial cellulose) and peptides (gelatin methacryloyl) to fabricate biomimetic scaffolds with layer-specific features for osteochondral defect repair. The biomimetic scaffolds exhibited a tightly bonded heterogeneous structure with cartilage layer incorporated TEMPO-oxidized bacterial cellulose (TOBC) nanofibers and subchondral bone layer augmented with enzymatically mineralized TOBC (m-TOBC) nanofibers, and stable mechanical properties. In vitro biological assessments demonstrated the exceptional biocompatibility of the biomimetic scaffold and enhanced chondrogenic/osteogenic differentiation of BMSCs. More importantly, the biomimetic scaffold significantly facilitated the effective reconstitution of both cartilage and subchondral bone tissues in a rat osteochondral defect model. Therefore, this biomimetic scaffold, designed based on natural biochemical and structural models, could serve as a promising material for osteochondral defect regeneration.
