Chondroitin sulfate cross-linked three-dimensional tailored electrospun scaffolds for cartilage regeneration

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, which were then cross-linked with chondroitin sulfate (CS) to further enhance their mechanical and biological performance. Afterwards, three-dimensional (3D) PLCL/SF scaffolds (3DS) and CS-crosslinked 3D scaffolds (3DCSS) with tailored size were successfully fabricated by an in-situ gas foaming in a confined mold followed by freeze-dried. Gas-foamed scaffolds displayed high porosity, rapid water uptake, and stable mechanical properties. While all of the scaffolds exhibited good cytocompatibility in vitro ; 3DCSS showed better cell seeding efficiency and chondro-protective effect compared to other scaffolds. Besides, 3DCSS scaffolds supported the formation of more mature cartilage-like tissues along with the best repair outcome in a rabbit articular cartilage defect model in vivo , as well as less expression level of pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α than that of the other groups. Taken together, 3DCSS may provide an alternative therapeutic option for cartilage tissue repair. • Chondroitin sulfate (CS) cross-linked gas-foamed scaffolds (3DCSS) were prepared by conjugate electrospinning and gas foaming. • 3DCSS possessed porous multi-layered structure and stable mechanical properties. • 3DCSS scaffolds induced neocartilage regeneration in vitro . • 3DCSS repaired articular cartilage defects in rabbits model in vivo . • 3DCSS reduced pro-inflammatory cytokines both in vitro and in vivo .