Probiotic-Functionalized Silk Fibroin/Sodium Alginate Scaffolds with Endoplasmic Reticulum Stress-Relieving Properties for Promoted Scarless Wound Healing

Bioactive substances such as probiotics are becoming a research hotspot in the field of tissue regeneration due to their excellent regulatory functions. Here, we proposed to load Lactobacillus casei onto a bilayer silk fibroin/sodium alginate (SF/SA) scaffold to endow the scaffold with both antibacterial and regenerative properties. The performance of the scaffold was characterized systemically. The L. casei-loaded scaffolds (L-SF/SA) bring in lactic acid, which has antibacterial and wound healing properties. In vitro, the cell-free supernatant (CFS) of L. casei inhibited the transformation of fibroblasts to myofibroblasts and relieved the endoplasmic reticulum stress (ERS). In vivo, L-SF/SA accelerated the healing of infected wounds in SD rats. The L-SF/SA reduced the bacterial load, induced M2 polarization of macrophages, increased angiogenesis, regulated collagen ratio, and alleviated the ERS, thereby promoting scarless wound healing and increasing hair follicle regeneration. Therefore, probiotic-functionalized silk fibroin/alginate scaffolds showed potential in the infected wound healing.