IGF1- and BM-MSC-incorporating collagen-chitosan scaffolds promote wound healing and hair follicle regeneration

Full-thickness skin injury affects millions of people worldwide each year. Although bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to promote cutaneous wound healing, they cannot functionally promote wound healing with the recovery of appendages such as hair follicles. We previously found that growth factor plus BM-MSCs could effectively promote wound healing and hair follicle regeneration. In the present study, we grafted insulin-like growth factor 1 (IGF1), a multifunctional cell growth factor, and BM-MSCs into a collagen-chitosan scaffold to investigate their effects on functional wound healing. Using scanning electron microscopy, histological staining, and quantitative analysis, we found that IGF1- and BM-MSC-incorporating collagen-chitosan scaffolds promote cutaneous wound healing with effective regeneration of hair follicles in a rat full-thickness skin injury model. In addition, IGF1/BM-MSCs inhibit inflammatory cytokines during wound healing. In vitro, we found that IGF1 promotes the proliferation and migration of BM-MSCs via the IGFR-mediated ERK1/2 signaling pathway. Collectively, in this study, we first demonstrated that IGF1 enhances BM-MSC-mediated wound healing as well as hair follicle regeneration. Our data suggest that the topical application of IGF1 and BM-MSCs incorporated in collagen-chitosan scaffolds can be used as a feasible and effective therapeutic approach to improve functional cutaneous wound healing.