Poster Z17 - Bio-ionic Hydrogel for Biodegradable, Ion-Conductive Peripheral Nerve Guides

Introduction: While peripheral nerves have some capacity for regeneration, the rate of regeneration is insufficient to restore function in many cases of peripheral nerve injury (PNI). Renervation following injury is impeded by axon apoptosis and muscle atrophy. Therefore, medical intervention is required to restore motor control in many cases of PNI. PNI are currently treated clinically using autografts. However, autografts are limited by the source and donor site morbidity. Biomaterial nerve conduits can be used to facilitate axon regrowth across large defects. Conductive biomaterials pose a particularly attractive option for fabrication of nerve guides due to their ability to conduct native electrical signals, accelerating axon extension. However, conductive materials commonly used for nerve conduit fabrication can be cytotoxic and have limited degradation in vivo. Using a biocompatible ionic liquid, we investigate the use of a biodegradable ion-conductive hydrogel in facilitating peripheral nerve regeneration.

Materials and

Methods: Conductive hydrogel nerve guide conduits were fabricated by photo-crosslinking of 10% acrylated bio-ionic liquid (Bio-IL) and 10% gelatin methacryloyl (GelMA) in an electrospun poly(lactide-co-caprolactone) conduit using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as a photoinitiator. Electrical conductivity was measured using potentiostatic. Biocompatibility of the hydrogels was assessed in vitro using a live/dead assay. Nerve conduits filled with Bio-IL/GelMA or GelMA were sutured to sciatic nerve defect in a rat model of peripheral nerve injury. Filled hydrogel nerve conduits were compared to empty nerve conduits. Rats receiving each conduit were analyzed for compound muscle action potential (CMAP), sensory response, gait, and gastrocnemius muscle structure at 8 weeks following injury.

Results, Conclusions, and Discussions: Hydrogels conjugated with 10% BioIL demonstrated a 2-fold increase in conductivity (5 x 10^(-4) S/m) over GelMA hydrogels. Further increases on BioIL concentration did not lead to further increase in conductivity. Therefore, 10% BioIL hydrogels were used in further fabrication of hydrogel conduits. Hydrogels with 10% BioIL demonstrated in vitro biocompatibility similar to GelMA hydrogels. At 8 weeks following implantation, BioIL/GelMA conduit animals saw improved CMAP compared to those implanted with empty conduits. BioIL/GelMA conduit implanted rats also demonstrated increased sensory response, and greater recovery of walking gait compared to GelMA filled conduit and empty conduit implanted animals. Mass of the gastrocnemius muscle from BioIL/GelMA animals experienced less decreased compared to GelMA or empty conduit implanted animals, demonstrating reduced muscle atrophy. Histological analysis of individual muscle fibers correlated with overall muscle mass findings, with greater decrease of fiber diameter in GelMA and empty conduit groups.
By conjugating of choline, an ionic biomolecule, to a hydrogel backbone we are able to fabricate a biocompatible hydrogel nerve conduit with increased conductivity. In a rat model of sciatic nerve injury, implantation of the BioIL/GelMA hydrogel conduits was able to improve functional recovery, as measured by CMAP, response to tactile sensory stimuli, and walking gait. Structural recovery of the muscle was also improved in BioIL/GelMA conduit group. Overall, results demonstrate that the use a BioiL conjugated, ion conductive nerve conduit may be used facilitate recovery in peripheral nerve injuries.

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