Implementation of Photosensitive, Injectable, Interpenetrating, and Kartogenin-Modified GELMA/PEDGA Biomimetic Scaffolds to Restore Cartilage Integrity in a Full-Thickness Osteochondral Defect Model.

Abstract

Cartilage defects caused by mechanical tear and wear are challenging clinical problems. Articular cartilage has unique load-bearing properties and limited self-repair ability. The current treatment methods, such as microfractures and autogenous cartilage transplantation to repair full-thickness cartilage defects, have apparent limitations. Tissue engineering technology has the potential to repair cartilage defects and directs current research development. To enhance the regenerative capacities of cartilage in weight-bearing areas, we attempted to develop a biomimetic scaffold loaded with a chondroprotective factor that can recreate structure, restore mechanical properties, and facilitate anabolic metabolism in larger joint defects. For enhanced spatial control over both bone and cartilage layers, it is envisioned that biomaterials that meet the needs of both tissue components are required for successful osteochondral repair. We used gelatin methacrylate (GELMA) and polyethylene glycol diacrylate (PEGDA) light-cured dual-network cross-linking modes that can significantly increase the mechanical properties of scaffolds and are capable of restoring function and prolonging the degradation time. Once the hydrogel complex was injected into the osteochondral defect, in situ UV light curing was applied to seamlessly connect the defect repair tissue with the surrounding normal cartilage tissue. The small molecule active substance kartogenin (KGN) can promote cartilage repair. We encapsulated KGN in biomimetic scaffolds so that, as the scaffold degrades, scaffold-loaded KGN was slowly released to induce endogenous mesenchymal stem cells to home and differentiate into chondrocytes to repair defective cartilage tissue. Our experiments have proven that, compared with the control group, GELMA/PEGDA + KGN repaired cartilage defects and restored cartilage to hyaline cartilage. Our study suggests that implementing photosensitive, injectable, interpenetrating, and kartogenin-modified GELMA/PEDGA biomimetic scaffolds may be a novel approach to restore cartilage integrity in full-thickness osteochondral defects.