Spatiotemporally controlled delivery of biological effectors from nanofiber scaffolds accelerates skin wound healing in porcine models
Xindan Zhang, Bowen Gong, Feng Rao, Hongtao Hu, Feng Tian, Yonglai Lu, Liqun Zhang, Younan Xia, Jiajia Xue
Abstract
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.