Hyaluronic acid-based biphasic scaffold with layer-specific induction capacity for osteochondral defect regeneration

The repair of cartilage and subchondral bone defects, especially the former, remains a challenge in clinical practice. An increasing number of studies have shown that the use of biomaterials has great advantages in regulating tissue repair, with lower cost and risk than the use of cytokines or cells. However, great challenges remain because of the marked differences between cartilage and subchondral bone. Here, biphasic osteochondral scaffolds with layer-specific differentiation were designed and developed. Hyaluronic acid (HA) was used as the matrix in the upper and lower layers, and differences in physicochemical properties and biological properties between the two layers were realized by different chemical crosslinking methods. The cartilage regeneration layer exhibited stress relaxation from the HA hydrazone crosslinking dynamics. Additionally, a porous HA hydrogel with dominant elasticity was prepared for subchondral bone repair. Importantly, a 3D-printed scaffold bracket could keep close integration of two layers and provided mechanical support, aiding the long-term tissue regeneration process. The in vitro and in vivo results indicated that the HA-base bilayer scaffold consisting of a dynamic HA layer and a porous HA layer realized the simultaneous integrated regeneration of articular cartilage and subchondral bone. Such scaffolds represent potential new materials for osteochondral regeneration.