Chondroitin Sulphate and Gas Foaming Concurrently Improve Articular Cartilage Regeneration in Electrospun Poly(L-lactide-co-ε-caprolactone)/Silk Fibroin Based Scaffolds

Degenerated cartilage tissues remain a burgeoning issue to be tackled, while bioactive engineering products available for optimal cartilage regeneration are scarce. In the present study, two-dimensional (2DS) poly(L-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF)-based scaffolds were fabricated by conjugate electrospinning method, and then cross-linked with chondroitin sulfate (CS) to further enhance their mechanical and biological performance. Afterwards, three-dimensional PLCL/SF scaffolds (3DS) and CS-crosslinked three-dimensional scaffolds (3DCSS) with tailored size were successfully fabricated by in situ gas foaming in a confined mold and subsequently freeze-dried. Gas-foamed scaffolds exhibited high porosity, rapid water absorption, and stable mechanical properties. While all of the scaffolds exhibited excellent cytocompatibility in vitro ; 3DCSS showed better cell seeding efficiency and chondro-protective effect as compared to the other scaffolds. Histological analysis of chondrocytes-seeded constructs after cultivation for up to 6 weeks in vitro also confirmed that 3DCSS scaffolds supported the formation of cartilage-like tissues along with the more secretion of cartilage-specific extracellular matrix than that of the other groups. The reparative potential of 3DCSS was further evaluated in an articular cartilage defect model in rabbits, which exhibited a well-integrated boundary and attenuated inflammation demonstrating less expression of pro-inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Taken together, the engineered biomimetic 3DCSS may provide a well-suited therapeutic option for cartilage tissue regeneration applications.