Biopolymer-nanotube nerve guidance conduit drug delivery for peripheral nerve regeneration: In vivo structural and functional assessment

Peripheral nerve injuries account for roughly 3% of all trauma patients with over 900,000 repair procedures annually in the US. Of all extremity peripheral nerve injuries, 51% require nerve repair with a transected gap. The current gold-standard treatment for peripheral nerve injuries, autograft repair, has several shortcomings. Engineered constructs are currently only suitable for short gaps or small diameter nerves. Here, we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine (4-AP) for peripheral nerve regeneration in a critical-size (15 mm) rat sciatic nerve transection model. The results of functional walking track analysis, morphometric evaluations of myelin development, and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft controls. Repaired nerves showed formation of thick myelin, presence of S100 and neurofilament markers, and promising functional recovery. The conduit's aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation, while the sustained release of 4-AP may increase nerve conduction, and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic factors. Overall, our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.
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Highlights • Nerve guidance conduit platform with tunable scaffold properties for repair and regeneration of large-gap nerve injuries. • Sustained 4-aminopyridine release amplifies neurotrophic factor release by Schwann cells to promote axon regeneration. • Longitudinally aligned scaffold pores and controllable physicochemical properties provide guidance for axon regeneration. • Critical-size rat sciatic nerve defect healing both structurally and functionally resembled autograft control treatment. • Innovative and transformative scaffold technology imbued with structural and functional features for tissue regeneration. • Scaffold enable tailorable release profiles for small molecules proteins and electrical stimulation for tissue regeneration.