Electroactive polypyrrole-coated nanofibrous scaffolds as stimuli-responsive platforms for skin tissue regeneration

Stimuli-responsive scaffolds have emerged as advanced platforms in tissue engineering by enabling dynamic interactions with the cell microenvironment. Among external stimuli, electrical cues are particularly relevant for skin regeneration, as endogenous bioelectric signals regulate cell migration, proliferation, and extracellular matrix deposition during wound healing. In this study, electrically conductive nanofibrous scaffolds were developed for skin tissue engineering by integrating biomimetic architecture, electroactive properties, and external electrical stimulation. Electrospun polycaprolactone and zein nanofibers were functionalized through in-situ polypyrrole polymerization, to obtain conductive scaffolds preserving fiber morphology, porosity, and mechanical properties. In-vitro experiments using human adipose-derived stem cells demonstrated that scaffold conductivity and electrical stimulation synergistically sustain cell viability compared to non-conductive substrates and unstimulated controls. Confocal microscopy revealed improved cell adhesion, elongation, and alignment, together with enhanced collagen type I deposition. Gene expression analysis showed selective upregulation of Col1A1 and CXCR4 in electrically stimulated conductive scaffolds, indicating increased extracellular matrix production and migratory signaling. To elucidate the electrical behavior of the system, finite element in-silico modeling was performed in both in-vitro culture wells and a rat wound model, demonstrating that conductive scaffolds modulate current density distributions, providing controlled electrical cues at the cell–material interface. In-vivo evaluation in a rat full-thickness skin wound model confirmed the safety and efficacy of the systems, showing accelerated wound closure, organized collagen deposition, dermal regeneration, and scaffold biodegradation without inflammatory responses. Overall, this integrated experimental and computational study highlights the potential of electrically stimulated conductive nanofibrous scaffolds as effective platforms for skin regenerative medicine.