Electrospun PLGA/PCL Nanofiber Film Loaded with LPA Promotes Full-Layer Wound Healing by Regulating the Keratinocyte Pyroptosis

Electrospun nanofibers have a number of qualities that make them a suitable choice for skin wound healing. Lysophosphatidic acid (LPA) stimulates the keratinocytes and fibroblasts to proliferate, differentiate, and migrate and enhances skin wound healing. Here, we developed the electrospun scaffolds contained in polycaprolactone (PCL) and polylactic-<i>co</i>-glycolic acid (PLGA). The scaffolds loaded with LPA nanoparticles retained a porous nanofiber structure and showed better physicochemical properties and biocompatibility. The scaffold continuously releases LPA to quickly initiate cell signaling and maintain long-term anti-inflammatory activity. In this study, we found that PP scaffold with LPA reduces the disordered collagen deposition and the thickness of the newborn epidermis, improves skin healing, and reduces scar formation. Explaining the mechanism of LPA mineralized tissue regeneration in skin wound healing, LPA inhibited the pyroptosis of keratinocyte, a cell death process that induces inflammation and scar formation by inhibiting the expression of TNF-α and β-catenin proteins. Thus, the electrospun PP scaffold with LPA can be potentially developed as a therapeutic avenue to target skin wound healing.