Smart conductive nanofibers integrating electrical stimulation for enhanced fibroblast alignment and collagen deposition in chronic wound repair

• Nanofibrous scaffolds doped with graphene showed enhance conductivity. • Scaffolds mechanical stiffness was mantained when subjected to repeated stresses in torsion and tension mode. • Conductive scaffolds, when exposed to ES, promoted in-vitro fibroblast alignment and supported cell adhesion and proliferation. • In-vivo lesions were fully re-epithelialized after 18 days when treated with conductive scaffolds in combination with ES Chronic skin wounds affect millions globally, causing significant patient morbidity and posing a major healthcare challenge. Conventional treatments, such as gauze dressings, wound debridement, and pressure off-loading, often fail to accelerate healing or reduce inflammation, resulting in low healing rates and frequent wound recurrence. Emerging studies evidenced the critical role of endogenous electric fields generated by transepithelial potentials in regulating cell migration and wound repair. The use of exogenous electrical stimuli aim to mimic these bioelectric cues, promoting fibroblast alignment, collagen deposition, angiogenesis, and re-epithelialization, thus promoting wound healing. Given these premises, this study focuses on the design and the development of electrospun nanofibrous scaffolds based on polycaprolactone and collagen, doped with conductive graphene nanosheets to support electrical current flow and enhance wound healing. High conductive and biocompatible graphene has been selected since it facilitates efficient electrical signal transmission and this should stimulate cellular responses, critical for tissue regeneration. The scaffolds were characterized for morphology, mechanical properties, degradation, surface wettability, zeta potential, and electrical conductivity. In-vitro assays confirmed scaffolds biocompatibility and fibroblast proliferation and adhesion onto the nanofibers with and without electrical treatment. Conductive Gr-loaded scaffolds in combination with electrical stimulation proved to support orientated aligned fibroblast growth. In-vivo studies on a murine model showed a significantly improved wound closure, tissue re-epithelialization and organized collagen deposition when the conductive scaffold was combined with external electrical stimulation.