Surfactin-reinforced gelatin methacrylate hydrogel accelerates diabetic wound healing by regulating the macrophage polarization and promoting angiogenesis

Abstract Chronic wound healing is a severe complication that threatens the life of diabetic patients because of the damaged skin microvasculature and prolonged inflammation at the wound site. Novel wound dressing materials with the outstanding wound repair specialty are highly needed. Herein, a new hydrogel was developed with attractive capabilities in stiffness, swelling, self-healing, and biocompatibility, for the treatment of chronic wound in diabetes. The hybrid hydrogel was achieved by firstly synthesizing gelatin methacrylate (GelMA), then microbial lipopeptide-surfactin (SF) together with the photoinitiator were added before being crosslinked with 60 s of UV (i.e., GelMA-SF hydrogels). With the increase of SF concentrations, the porosity and tensile modulus of GelMA-SF hydrogels decreased, while the ultimate stress and compression modulus significantly increased compared with GelMA hydrogels. The feasibility of GelMA-SF hydrogels was tested by treating skin wounds in type I diabetic rats without coverage in vivo. For the first time, the study introduced SF to the GelMA network and revealed the mechanisms of the GelMA-SF hydrogels to promote diabetic wound healing via regulating macrophage polarization and promoting angiogenesis. The dynamic multifunctional hydrogel materials show great promise in the regeneration of difform wounds, especially, in situations with impaired angiogenesis and persistent inflammatory responses.