Multifunctional electrospun PCL/CNT/EGCG nerve conduits with a collagen hydrogel for enhanced sciatic nerve regeneration

Damage to peripheral nerves results in sensory, motor, and autonomic impairments, which are frequently accompanied by neuropathic pain. Effective strategies for nerve regeneration remain a major clinical challenge. We engineered nanofibrous nerve guidance conduits (NGCs) composed of poly(ε-caprolactone) (PCL), multiwalled carbon nanotubes (CNTs), and epigallocatechin gallate (EGCG), which were fabricated by electrospinning and subsequently filled with a collagen hydrogel. CNTs were incorporated to improve the mechanical strength, physicochemical properties, and electrical conductivity, whereas EGCG had anti-inflammatory and antioxidant effects. The scaffold morphology was evaluated by scanning electron microscopy (SEM) and atomic force microscopy (AFM). In vitro assays were used to assess mesenchymal stem cell (MSC) viability and morphology. Functional recovery was examined via sciatic nerve functional indices and gastrocnemius electromyography. At 12 weeks post-axotomy, stereological, immunohistochemical, MRI, and real-time PCR analyses of sciatic nerves and L4–L5 dorsal root ganglia revealed significant upregulation of neuronal markers (MAP2, β-tubulin III, and neurofilament) and Schwann cell markers (S100, and NF-200), suggesting enhanced neuronal maturation and myelination. Compared with the control conditions, the composite conduits promoted improved motor function, nerve conduction velocity, and muscle preservation. PCL/CNT/EGCG nanofibrous conduits, combined with a collagen hydrogel provide a favorable microenvironment for peripheral nerve regeneration. This strategy has translational potential for improving outcomes following peripheral nerve injury.