Development of a bioactive, piezoelectric PVDF-TrFE scaffold with evaluation of tissue reaction for potential in nerve repair

Current biomaterials for trauma-associated tissue repair often fail to recapitulate the complex signaling environment required for effective integration and regeneration, particularly in modulating immune responses post-implantation. To address these limitations, we developed a multi-cue electrospun scaffold incorporating physiologically relevant chemical, electrical, and physical signals. Using blend electrospinning, we functionalized poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) with cell-secreted, decellularized extracellular matrix (dECM) to enhance cellular responses and limit foreign body reactions. The resulting scaffolds were systematically characterized <i>in vitro</i> for their structural, biochemical, and piezoelectric properties, and evaluated for their ability to support Schwann cell adhesion, metabolism, and repair-associated morphology in the context of peripheral nerve injury (PNI). <i>In vivo</i> subcutaneous implantation in rats demonstrated reduced foreign body giant cell formation at 7 days, and by 28 days, signs of regenerative healing, including vascularization and nerve tissue formation, were observed near the implantation site. Overall, these dECM-integrated PVDF-TrFE scaffolds effectively modulate immune responses and promote regenerative cell phenotypes. This work highlights the potential of bioactive, electroactive, and biomimetic scaffolds as next-generation implantable platforms for tissue engineering and repair.