| Skin, as the largest organ of the body, provides many essential functions. However, deep and extensive burns or "hard-to-heal" wounds can significantly compromise the health and well-being of the patients. Considering the limited availability and potential harvesting-induced morbidity of autografts, tissue-engineered autologous skin grafts would be an ideal alternative to address these challenges without immunorejection. However, current skin substitutes often suffer from a range of problems and the lack of suitable scaffold that can recapture the key features of native skin tissue is the most important one.;Utilization of biomimetic nanofibers for wound repair holds great promise due to their morphological and dimensional similarity to the native extracellular matrix (ECM). Electrospinning, a high voltage-driven spinning technique, enables cost-effective fabrication of nanofibers from versatile materials. Numerous progresses have been made to fabricate and characterize various nanofibers for wound repair and generation of skin grafts. However, little is known about how cell-residing microenvironments regulate the cellular responses and the associated mechanisms. In our studies, we explored the effects of several nanofiber properties, including fiber spatial arrangement, composition and topography of the fiber meshes on the phenotypic expression of human skin cells in relation to wound healing. We found that skin cells could detect and response to those subtle variations of nanofibers. For the first time, the associated nanofiber-induced signaling with such regulations was investigated. By intervening the integrin and TGF-β signaling, nanofibers differentially regulate the cellular responses related to wound healing. Based on our findings, nanofibers with optimal properties for wound healing could be adopted for the design of next-generation tissue-engineered skin grafts or wound dressing. |
