Enhanced osteochondral repair with hyaline cartilage formation using an extracellular matrix-inspired natural scaffold

Osteochondral defects pose a great challenge and a satisfactory strategy for their repair has yet to be identified. In particular, poor repair could result in the generation of fibrous cartilage and subchondral bone, causing the degeneration of osteochondral tissue and eventually leading to repair failure. Herein, taking inspiration from the chemical elements inherent in the natural extracellular matrix (ECM), we proposed a novel ECM-mimicking scaffold composed of natural polysaccharides and polypeptides for osteochondral repair. By meticulously modifying natural biopolymers to form reversible guest–host and rigid covalent networks, the scaffold not only exhibited outstanding biocompatibility, cell adaptability, and biodegradability, but also had excellent mechanical properties that can cater to the environment of osteochondral tissue. Additionally, benefiting from the drug-loading group, chondrogenic and osteogenic drugs could be precisely integrated into the specific zone of the scaffold, providing a tissue-specific microenvironment to facilitate bone and cartilage differentiation. In rabbit osteochondral defects, the ECM-inspired scaffold not only showed a strong capacity to promote hyaline cartilage formation with typical lacuna structure, sufficient mechanical strength, good elasticity, and cartilage-specific ECM deposition, but also accelerated the regeneration of quality subchondral bone with high bone mineralization density. Furthermore, the new cartilage and subchondral bone were heterogeneous, a trait that is typical of the natural landscape, reflecting the gradual progression from cartilage to subchondral bone. These results suggest the potential value of this bioinspired osteochondral scaffold for clinical applications.