PLGA/SF/linagliptin wound matrix-induced membrane promotes diabetic wounds healing by inhibiting macrophage...

Diabetic wounds often exhibit delayed healing because of persistent inflammation, thus, remaining in the inflammatory phase. A key factor driving the delayed healing is pyroptosis, a proinflammatory form of programmed cell death which leads to the excessive release of inflammatory mediators. And macrophages are deeply involved in the entire process of wound inflammation. In this study, to regulate the pathological inflammation, we developed linagliptin-loaded hybrid PLGA [Poly(lactic-co-glycolic acid)]/SF(Silk Fibroin) membranes by electrostatic spinning. This advanced biomaterial with suitable physicochemical properties and biocompatibility is designed to provide a sustained release of linagliptin. Our in vitro experiments demonstrated that linagliptin effectively suppresses the macrophage pyroptosis through the noncanonical pathway, thereby reducing the secretion of key pro-inflammatory factors and improving the function of cells involved in wound healing. Furthermore, our in vivo experiments demonstrated that the PLGA/SF/linagliptin membrane promotes the healing of diabetic wounds and shortens the inflammatory phase of wounds, while improving skin regeneration. The collective results confirm the linagliptin's capacity to inhibit nonclassical pyroptosis and the PLGA/SF/linagliptin wound matrix-induced membrane's potential to promote wound healing. In conclusion, we have developed a novel wound matrix-inducing membrane with slow linagliptin release that promotes chronic wound healing by modulating macrophage pyroptosis.