Spatiotemporally controlled delivery of biological effectors from nanofiber scaffolds accelerates skin wound healing in porcine models

Skin wound healing is a dynamic process, yet scaffolds enabling stage-specific modulation remain limited. We fabricated a nanofiber scaffold from FDA-approved materials, consisting of two outer layers of radially aligned and random poly(ε-caprolactone) fibers and a middle layer of electrosprayed phase-change microparticles loaded with platelet-derived growth factor-BB (PDGF-BB)/vascular endothelial growth factor (VEGF) in the periphery and PDGF-BB/epidermal growth factor (EGF) in the center. Near-infrared irradiation through a photomask enabled spatiotemporal control of growth factor release, aligning PDGF-BB, VEGF, and EGF delivery with specific phases of wound healing to promote vascularization, cell proliferation, and tissue remodeling. In a preclinical porcine model, it enhanced closure and modulated the microenvironment by activating PI3K-Akt, MAPK, and immune pathways, up-regulating genes for survival and repair while down-regulating those linked to apoptosis and inflammation. With scalable manufacturing and large-animal efficacy, this scaffold holds translational potential for skin wound healing.