Spatiotemporally Delivery of Multiple Growth Factors from Electrospun Scaffolds through Photothermal Effect to Manipulate Skin Wound Regeneration

Due to the increasing incidence of full-thickness skin injuries caused by mechanical trauma, burns, as well as conditions like diabetes and malignant tumors, the repair of skin wounds has become a major medical challenge in the field of wound healing. During the process of skin wound repair, different types of growth factors play specific roles at various stages, collectively promoting wound healing. In this study, we fabricated a nanofiber scaffold with surface topographical features using electrospinning. Furthermore, the scaffold was functionalized to provide the required microenvironment for skin wound repair by incorporating growth factors. To enable the spatiotemporal controlled release of these growth factors, we combined photothermal therapy with phase change materials and introduced a photomask strategy. Specifically, a three-layered sandwich-like photothermal scaffold was prepared by in conjunction with coaxial electrospraying, using polycaprolactone as the base material. The scaffold consisted of an inner layer of radially aligned nanofibers, an outer layer of random nanofibers, and an intermediate layer containing growth factors and photothermal agents in the form of phase change microspheres. By utilizing near-infrared light irradiation and the photomask strategy, the spatiotemporal controlled release of the growth factors was achieved. The multi-layered structure of the scaffold was confirmed by surface morphology analysis, and the modified surface was found to promote cell adhesion according to water contact angle measurements. Photothermal experiments and studies on growth factor release demonstrated that the scaffold could achieve spatiotemporal controlled release while maintaining photothermal stability, and the released growth factors retained their pro-angiogenic activities. <i>In vitro</i> experiments showed that the scaffold not only promoted cell proliferation but also facilitated cell migration through the combination of its topographical surface and the spatiotemporal controlled release of growth factors. Finally, an animal full-thickness skin wound model was employed to evaluate the wound healing effectiveness of the scaffold, revealing the regulatory patterns and effects of growth factors <i>in vivo</i> under programmable photothermal stimulation. In conclusion, the nanofiber scaffold with photothermal-triggered controlled release of growth factors effectively integrates the topographical structure of the nanofibers with the controllable release of growth factors. It provides a novel approach for the design of skin wound repair scaffolds and their combination with photothermal therapy to promote skin wound healing. This research holds significant potential in the fields of tissue regeneration and controlled release.