Three-dimensional porous gas-foamed electrospun nanofiber scaffold for cartilage regeneration.

To achieve optimal functional recovery of articular cartilage, scaffolds with nanofibrous structure and biological function have been widely pursued. In this study, two-dimensional electrospun poly(l-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF) scaffolds (2DS) were fabricated by dynamic liquid support (DLS) electrospinning system, and then cross-linked with hyaluronic acid (HA) to further mimic the microarchitecture of native cartilage. Subsequently, three-dimensional PLCL/SF scaffolds (3DS) and HA-crosslinked three-dimensional scaffolds (3DHAS) were successfully fabricated by in situ gas foaming and freeze-drying. 3DHAS exhibited better mechanical properties than that of the 3DS. Moreover, all scaffolds exhibited excellent biocompatibility in vitro. 3DHAS showed better proliferation and phenotypic maintenance of chondrocytes as compared to the other scaffolds. Histological analysis of cell-scaffold constructs explanted 8 weeks after implantation demonstrated that both 3DS and 3DHAS scaffolds formed cartilage-like tissues, and the cartilage lacuna formed in 3DHAS scaffolds was more mature. Moreover, the reparative capacity of scaffolds was discerned after implantation in the full-thickness articular cartilage model in rabbits for up to 12 weeks. The macroscopic and histological results exhibited typical cartilage-like character and well-integrated boundary between 3DHAS scaffolds and the host tissues. Collectively, biomimetic 3DHAS scaffolds may be promising candidates for cartilage tissue regeneration applications.