Biofabrication of osteochondral composite scaffolds: advances in multi-material bioprinting, functional microenvironment engineering and orthopedic translation.

Abstract

Osteochondral defects are challenging to repair due to the complex structure of the osteochondral unit. Current clinical methods often fail to achieve long-term cartilage-bone integration. Recent advances in multi-material bioprinting enable the construction of biomimetic scaffolds with graded architectures and region-specific functions. This review summarizes progress in biofabricating osteochondral composite scaffolds, focusing on multi-material bioprinting and zonal microenvironment engineering. Key topics include bioink design, gradient scaffold architectures, hybrid manufacturing, spatiotemporal delivery systems, multicellular biofabrication, vascularization, immunomodulation, and stimuli-responsive biomaterials. We also discuss in vitro and in vivo evaluation approaches and major translational barriers such as mechanical mismatch, long-term stability, scalability, and regulatory issues. The integration of multimaterial bioprinting, adaptive biomaterials, and programmable microenvironments may facilitate the development of osteochondral implants with improved tissue integration and translational potential. Future studies should prioritize long-term osteochondral integration, vascular coordination, manufacturing reproducibility, and clinically relevant validation.