| Peripheral nerve injury is a relevant clinical concern. Although surgical management of these injuries has improved over time, the current "gold standard" for nerve transection injury, autograft, has many limitations. Nerve conduits are used as an alternative to autograft surgery but they are currently recommended for the repair of small defects (≤ 3cm) in small diameter sensory nerves only. Use of filler materials inside the conduit have been shown to increase the defect size in which conduits can be effective and can result in greater functional recovery in animal models.;This work uses a novel conduit filler derived from a human hair keratin biomaterial hydrogel with the goal of promoting the clinical translation of an effective alternative to autograft surgery. The work consists of 3 aims based upon the hypothesis that keratin hydrogel enhances peripheral nerve regeneration by early cellular interactions in the injured peripheral nervous system: 1) To demonstrate the efficacy of the keratin hydrogel in a clinically relevant non-human primate model 2) To investigate the keratin hydrogel's effect on inflammatory and regenerative cells in the injured peripheral nervous system using a rat sciatic nerve study 3) To characterize keratin's influence on cellular interactions using a simplified culture system.;Methods for this work include nerve conduction studies by electrophysiology, functional testing, histology and histomorphometry of nerve and muscle tissue, immunogenicity testing, isolation and culture of primary Schwann cells, and in vitro proliferation, migration, and cytokine expression assays.;Electrophysiological and histological outcome measures in the non-human primate study showed that keratin hydrogel significantly enhanced median nerve regeneration over 12 months compared to a saline control. The rat study and in vitro assays provided evidence that keratin hydrogel influences peripheral nervous system cellular response to injury and that this altered cellular response may contribute to enhancement of peripheral nerve regeneration. Future work based on the studies in this document may ultimately result in a clinically available alternative to autograft surgery for peripheral nerve injury patients. |
