Silk gel recruits specific cell populations for scarless skin regeneration

Scarless skin regeneration is not achieved although various biomaterials have been investigated on trial-and-error manner. There is no predictable way to link a specific biomaterial with in vivo cell populations which dominate the skin repair. In this study, single-cell RNA sequencing was conducted to investigate the cellular mechanism of two prevailing biomaterials used in skin regeneration, silk fibroin gel and alginate gel. We found that these two gels induced different cell population structures in vivo. Compared with the alginate-derived hydrogel, silk fibroin-derived hydrogel induced more pro-regenerative macrophages and recruited more hair follicle stem cells, which contributed to almost scarless skin regeneration. Besides, an off-the-shelf silk gel scaffold was fabricated and exhibited more efficacy than autologous skin grafts in porcine models. These findings exhibited the promises of the silk gel for skin regeneration and illustrated a predictable strategy for biomaterial selection based on cell populations recruitment.