Bioinspired Aligned Electroconductive Hydrogel Nanofiber Patch Enhances Peripheral Nerve Repair through Mechanosensitive Calcium Influx and Focal Adhesion Kinase/Protein Kinase B Pathway Activation.

Abstract

Peripheral nerve injury (PNI) results in the loss of motor function and sensory perception. Effective repair of the injured peripheral nerves hinges on the coordinated actions of Schwann cell recruitment, neurite outgrowth, and immunoregulation. Herein, we develop an electroconductive and immunomodulatory nerve patch composed of collagen-like aligned hydrogel nanofibers. This patch is constructed using electrospinning and photo-crosslinking, followed by tannic acid (TA) and poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) modification to impart antioxidant and electroconductive properties. TA modification significantly enhances substrate surface hydrophilicity, fosters cell adhesion and spreading, alleviates the toxic effects of inflammation on cells. Although PEDOT:PSS deposition decreases substrate hydrophilicity, it exhibits no significant effect on cell spreading and oxidation resistance. Moreover, it effectively improves electroconductive features and accelerates neuronal differentiation through mechanosensor-mediated calcium and focal adhesion kinase/protein kinase B (FAK/AKT) pathways. In vivo experiments using a rat sciatic nerve injury model demonstrate that the bioinspired patch maintains close conformal contact with the injured nerve and form a tightly coupled electrical bridge with the electroresponsive neural tissue. This ultimately facilitates nerve regeneration and enables both anatomical and functional recovery without evident muscle atrophy. Collectively, our findings highlight the potential of the bioinspired patch as a promising platform for enhancing PNI repair. STATEMENT OF SIGNIFICANCE: Bioinspired materials that mimic the native extracellular matrix (ECM) represent a promising strategy for peripheral nerve injury (PNI) repair by supporting endogenous neurogenesis and guiding tissue regeneration. Herein, we developed an electroconductive and immunomodulatory nerve patch consisting of collagen-like aligned hydrogel nanofibers, sequentially functionalized with tannic acid (TA) and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) to introduce antioxidant and electroconductive capabilities. This bioinspired patch effectively promoted cell adhesion and spreading, mitigated immune responses, and established a stable electrical interface with electroresponsive neural tissues, ultimately accelerating neuronal differentiation and regeneration by activating the mechanosensor-mediated calcium and focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathways. Our findings highlight this functionalized patch as a promising platform for enhancing PNI repair.