Biomimetic Construction of a Biphasic Scaffold with Hierarchical Porous Structures and Topographical Interfaces for Osteochondral Repair

Cartilage is difficult to self-repair, and it is a great challenge in clinical practice. Herein, we developed a biomimetic biphasic scaffold with hierarchical porous structures and functionalized topographical interfaces for osteochondral repair. The hierarchical structures with macro/micro/nano scaffolds were fabricated via a combination of 3D printing and hydrothermal treatment. The cartilage phase (cartilage scaffold) was composed of a SilMA hydrogel (mimicking the compositional and mechanical properties of native cartilage), while the bone phase was a 3D-printed hydroxyapatite (HAp) porous scaffold (mimicking the mineral phase of subchondral bone). Then, the osteochondral interface was constructed by integrating the two phases through photo-cross-linking, forming a continuous and stable connection between the cartilage and bone layers. Mechanical tests confirmed that the biphasic scaffold possessed excellent load-bearing capacity, matching the biomechanical requirements of the osteochondral tissue microenvironment. In vitro experiments demonstrated that the scaffold effectively promoted the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes and osteoblasts, as evidenced by the enhanced expression of chondrogenic (Collagen II, Aggrecan) and osteogenic (Collagen I, Osteocalcin) markers. Furthermore, in vivo evaluations in an osteochondral defect model revealed significant regeneration of hyaline cartilage-like tissue in the cartilage phase and robust formation of subchondral bone in the bone phase, with a well-integrated osteochondral interface. Collectively, this study indicates that the biomimetic biphasic scaffold with hierarchical porous structures and topographical interfaces provides a promising therapeutic strategy for articular cartilage regeneration, offering potential clinical application value for osteochondral defect repair.