Innovative spiral nerve conduits: Addressing nutrient transport and cellular activity for critical-sized nerve defects

Large-gap nerve defects require nerve guide conduits (NGCs) for complete regeneration and muscle innervation. Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration. Still, most are tubular with inadequate pore sizes and lack surface cues for nutrient transport, cell attachment, and tissue infiltration. This study developed a porous spiral NGC to address these issues using a 3D-printed thermoplastic polyurethane (TPU) fiber lattice. The lattice was functionalized with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun aligned (aPHBV) and randomly (rPHBV) oriented nanofibers to enhance cellular activity. TPU lattices were made with 25 %, 35 %, and 50 % infill densities to create scaffolds with varied mechanical compliance. The fabricated TPU/PHBV spiral conduits had significantly higher surface areas (25 % TPU/PHBV: 698.97 mm 2 , 35 % TPU/PHBV: 500.06 mm 2 , 50 % TPU/PHBV: 327.61 mm 2 ) compared to commercially available nerve conduits like Neurolac™ (205.26 mm 2 ). Aligned PHBV nanofibers showed excellent Schwann cell (RSC96) adhesion, proliferation, and neurogenic gene expression for all infill densities. Spiral TPU/PHBV conduits with 25 % and 35 % infill densities exhibited Young's modulus values comparable to Neurotube® and ultimate tensile strength like acellular cadaveric human nerves. A 10 mm sciatic nerve defect in Wistar rats treated with TPU/aPHBV NGCs demonstrated muscle innervation and axon healing comparable to autografts over 4 months, as evaluated by gait analysis, functional recovery, and histology. The TPU/PHBV NGC developed in this study shows promise as a treatment for large-gap nerve defects. • Development of polymeric spiral micro-nanostructured nerve guidance conduits designed for large-gap nerve regeneration. • Tissue-pliant thermoplastic TPU spiral structure with aligned PHBV nanofibers to enhance transport and axon guidance. • Conduits offer controllable properties such as mechanical strength and surface topography for guiding axon regeneration. • Conduits promote Schwann cell proliferation, alignment, and neurotrophic factor secretion essential for axonal regrowth. • The nerve healing outcome in a rat sciatic nerve defect structurally and functionally resembled the autograft controls.