Topographical design principles for osteochondral tissue engineering

The osteochondral unit has a complex hierarchical structure where cartilage and subchondral bone show different physical, chemical, and functional properties. Replicating this structure remains a major challenge in osteochondral tissue engineering. Among various scaffold design factors, surface topography has emerged as a powerful regulator of cell behavior, but its rational integration into osteochondral constructs is still limited. This review systematically explores how topographical features affect cartilage and bone regeneration, focusing especially on feature size and anisotropy. Evidence across in vitro and in vivo studies indicates that nanoscale topographies better support chondrogenic differentiation and cartilage-like extracellular matrix formation by resembling natural cartilage, with isotropic features helping maintain chondrocyte shape. In contrast, microscale features tend to promote osteogenic differentiation, mineralization, and bone tissue organization, although osteogenic responses have also been observed on certain nanoscale topographies that mimic trabecular bone spaces. Anisotropic topographies further improve tissue-specific responses by guiding cell alignment and promoting organized matrix deposition across both cartilage and bone regions. Overall, these results highlight surface topography as a key design parameter for coordinating osteochondral regeneration. These complementary effects suggest that combining multi-scale and spatially graded topographies could imitate natural tissue architecture, enabling coordinated regeneration of cartilage and bone and offering a promising approach for functional osteochondral repair. Therefore, this review outlines practical design principles to guide the development of next-generation biomaterials for functional osteochondral repair.