Electroactive electrospun nanoplatform combined with electrical stimulation modulates anti-inflammatory macrophage polarization for enhanced wound healing.

Introduction: Immune regulation is critical for tissue repair, particularly through the polarization of anti-inflammatory macrophages. While biological and chemical stimuli can modulate macrophage polarization, the effects of physical stimuli remain underexplored. This study investigates the use of an electroactive nanofibrous scaffold combined with exogenous electrical stimulation (ES) to modulate macrophage polarization for tissue regeneration. Methods: An electroactive, aligned nanofibrous scaffold composed of polyurethane and carbon nanotubes (PU/CNT) was fabricated via electrospinning. Its ability to modulate macrophage polarization was assessed in vitro and in vivo under exogenous ES. Evaluations included biocompatibility tests, analysis of macrophage phenotype-specific gene (Arg1, IL-10, TNF-α, IL-6) and protein (IL-10) expression via qPCR, ELISA, and immunohistochemistry, and in vivo wound healing assessment. Results: The nanofibrous scaffold exhibited excellent conductivity and good biocompatibility both in vitro and in vivo. Exogenous ES significantly promoted the polarization of macrophages toward the anti-inflammatory M2 phenotype. This was confirmed by the upregulation of M2-associated genes (Arg1, IL-10) and the protein IL-10, alongside the downregulation of M1-associated genes (TNF-α, IL-6). Discussion: This work establishes that the conductive PU/CNT scaffold can effectively deliver exogenous ES to polarize macrophages toward a regenerative phenotype. It provides a novel strategy for immune modulation and a promising tool for advancing macrophage-based therapies in tissue engineering.