Bilayer Hydrogel Scaffold with Directional Micro‐Channels and Mechanical Gradient to Promote Osteochondral Repair

Osteochondral defect is a severe health concern, particularly in the elderly, while, with limited medical treatment options. It is urgent to develop osteochondral regeneration scaffolds that integrate multiple biological cues to promote cartilage and subchondral bone repair simultaneously. In this study, osteochondral scaffolds featuring both a mechanical gradient and unidirectional micro-channels are constructed based on a bilayer hydrogel design. The soft layer, composed of a polymeric double network, mimics the mechanical properties of cartilage. The relatively stiff layer, reinforced with nanohydroxyapatite (nHAp), aligns with the subchondral bone feature. The combination of bilayer structure provides a mechanical cue to mimic the heterogeneous modulus of the native osteochondral tissue. The bilayer design contributes to the differentiation of bone mesenchymal stem cells (BMSCs) into chondrocytes and osteoblasts, correspondingly. Moreover, the unidirectional micro-channels crossing the bilayer provide a topological cue, which facilitates the directional migration of cells. In vivo implanting in a rat osteochondral injury model demonstrates enhanced regeneration of cartilage and bone after 12 weeks. These findings suggest that the bilayer hydrogel scaffold, through the integration of mechanical and topological cues, offers a biomimetic 3D extracellular matrix with promising potential for osteochondral repair.