Sustained release of inhibitor from bionic scaffolds for wound healing and functional regeneration

Small molecules play remarkable roles in promoting tissue regeneration, but are limited by their burst release. Small molecules such as deferoxamine (DFO) have been released slowly from silk hydrogels and stimulated angiogenesis and wound healing, but failed to achieve functional recovery of skin. Various bioactive molecules are required to create a suitable niche for better skin regeneration by controlling their release behaviors. Herein, a small molecule SB216763, a GSK-3 inhibitor, was loaded on silk fibroin nanofibers (SNF), and then mixed with chitosan (CS) to prepare the small molecule-loaded composite bionic scaffolds (CSNF-SB). Given the interaction of SNF and SB216763, the sustained release of SB216763 for more than 21 days was achieved for SNF and CSNF-SB composite scaffolds. Compared to drug-free CSNF scaffolds, CSNF-SB showed better cell adhesion and proliferation capacity, suggesting bioactivity. The upregulated expression of β-catenin in fibroblasts in vitro revealed that the released small molecules maintained their function in composite scaffolds. Quicker and better wound healing was realized with the drug-loaded scaffolds, which was significantly superior to that treated with drug-free scaffolds. Unlike the DFO-loaded silk hydrogel system, hair follicle neogenesis was also found in the drug-loaded-scaffold treatment wounds, demonstrating functional recovery. Therefore, silk nanofibers as versatile carriers for different small bioactive molecules could be used to fabricate scaffolds with optimized niches and then achieve functional recovery of tissues. The small molecule-loaded bionic scaffolds have a promising future in skin tissue regeneration.