3D bioprinted scaffolds for osteochondral regeneration: advancements and applications

Osteochondral defects, involving concurrent damage to articular cartilage and subchondral bone, pose significant clinical challenges due to their complex hierarchical structure and limited self-healing capacity. Traditional repair strategies often fail to replicate the biomechanical and biological gradients inherent to native osteochondral tissue, leading to suboptimal outcomes. Three-dimensional (3D) bioprinting has emerged as a transformative approach, enabling precise spatial deposition of biomaterials, cells, and signaling factors to construct biomimetic scaffolds with tailored gradients. This review systematically examines the physiological and pathological features of osteochondral units, emphasizing their zonal heterogeneity in extracellular matrix composition, mechanical properties, and cellular organization. Advancements in 3D bioprinting technologies are examined, and their efficacy in fabricating multi-layered and gradient scaffolds is evaluated. Key components of bioinks are discussed, focusing on optimizing bioink rheology, biocompatibility, and functional integration. Innovative strategies for embedding biochemical cues and designing continuous structural gradients are explored to address challenges in interfacial stress distribution and cell differentiation control. Furthermore, the design principles of biomimetic gradient scaffolds are highlighted for their critical role in facilitating osteochondral tissue regeneration. Finally, future directions are proposed, including high-resolution volumetric bioprinting, dynamic biomaterial development, and gene-activated scaffolds, aiming to bridge the gap between laboratory innovation and clinical application in osteochondral regeneration. This comprehensive analysis provides a roadmap for advancing 3D bioprinted solutions toward functional restoration of complex osteochondral defects.