Biocompatible, Ion-Conductive Hydrogel-Filled Nerve Conduit for Peripheral Nerve Regeneration

Peripheral nerve injury can result in a loss of sensation and muscle control. Native axon regeneration rates are insufficient to bridge a large gap due to severe damage, leading to a permanent loss of function. Contemporary use of autografts as a treatment, while effective, is limited by donor-site morbidity. Conductive nerve guides can provide mechanical support for regenerating axons, while electrical conductivity provides bioelectrical cues. However, conventional materials used to provide electrical conductivity to hydrogels are not biodegradable and can induce inflammation, which can further impede regeneration. To address these issues, a biodegradable conductive hydrogel containing choline-based bioionic liquid (BioIL) was designed to bridge large nerve gaps and support native axon regeneration. Choline, a small molecule precursor of various biomolecules, combined with a gelatin-based hydrogel, creates a biodegradable and resorbable hydrogel. Conjugation of BioIL to a gelatin methacrylol (GelMA) hydrogel, followed by saline submersion, imparted an ionic conductivity to the hydrogel. Ion-conductive GelMA/BioIL hydrogels supported the myelination function of Schwann cells and the axon outgrowth from dorsal root ganglia in vitro. Implantation of GelMA/BioIL-filled poly(l-lactide-co-caprolactone) nerve conduit in a rat model of peripheral nerve injury improved the recovery of motor and sensory function. The engineered GelMA/BioIL hydrogel increased the number of regenerated axons, improved the myelination of regenerated axons, and reduced the atrophy of downstream muscle. These results support the use of a BioIL-functionalized hydrogel in creating effective, biocompatible nerve conduits for peripheral nerve regeneration.