PLGA nanofibers carrying rhFGF1 for the effective treatment of skin wounds in diabetic mice

Diabetic foot ulcers are among the most common complications of diabetes and can lead to delayed wound healing. Fibroblast growth factor (FGF1) is a classic drug for the treatment of skin wounds but has the disadvantages of a short half-life and instability. Poly (lactic-co-glycolic acid) (PLGA) nanofibers are sustained-release biomaterials that have potential for use as therapeutic delivery systems. However, the therapeutic effect of PLGA loaded with recombinant human FGF1 (rhFGF1) on diabetic wound healing is unknown. Therefore, this study aimed to explore the therapeutic effects of PLGA-rhFGF1 in type 2 diabetic (T2D) wound mice. We found that PLGA offers good sustained release, which enhances the stability and bioactivity of rhFGF1. PLGA-rhFGF1 promoted wound closure, re-epithelialization and the expression of keratin 10 and keratin 14 in T2D mice on day 14. PLGA-rhFGF1 significantly decreased the levels of TNF-α and IL-6 in serum and skin tissues as well as the level of IL-1β in skin tissues. Moreover, PLGA-rhFGF1 decreased the mRNA levels of CXCL1, MCP1 and MIP2, and the fluorescence intensity of F4/80 and Ly6G in T2D wound mice and increased the collagen content and the protein expression of collagen I in the dermis of T2D wounds. PLGA-rhFGF1 also increased blood flow; the mRNA levels of the angiogenesis-related factors VEGF, Ang-1 and eNOS and the fluorescence intensity of CD31 in T2D wound mice. These data indicate that PLGA releases rhFGF1 slowly and promotes skin wound healing in T2D mice. The mechanisms through which PLGA-rhFGF1 produces these effects involve decreased inflammation and the promotion of granulation, re-epithelialization and angiogenesis.