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,… Click to show full abstract
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 in vitro 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). In vivo 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.