Peripheral Nerve Regeneration Using a Keratin-Based Scaffold: Long-Term Functional and Histological Outcomes in a Mouse Model

Abstract

The management of peripheral nerve injuries with segmental defects is a challenge to both patient and surgeon. Repairs under tension have a poor prognosis; sensory nerve allografts have donor site morbidity and suboptimal motor recovery, but remain the gold standard. The development of conduit-based repair strategies has evolved and these are promising for sensory nerves and short defects; however, no conduit filler is clinically available that improves motor recovery equivalent to sensory autografts. In this study, motor recovery using keratin-based hydrogel filler was compared with that for sensory nerve autografts and empty conduits. Fifty-four mice were randomized into 3 treatment groups: empty conduit, sural nerve autograft, and keratin hydrogel-filled conduit. Animals were followed for 6 weeks, 3 months, and 6 months. Outcomes included compound motor action potential (CMAP), nerve area, myelinated axon number and density, and myelinated axon diameter. Neuromuscular recovery with keratin was greater than with empty conduits in most outcome measures. Nerves that regenerated through the keratin hydrogel had lower conduction delays, greater amplitudes, more myelinated axons, and larger axons than nerves that regenerated through empty conduits. Sensory nerve autografts and keratin hydrogel were statistically equivalent in CMAP measurements at 6 months. Moreover, keratin-filled conduits demonstrated greater axon density and larger average axon diameter than both empty conduits and autograft at 6 months. In a mouse tibial nerve model, keratin hydrogels significantly improved electrophysiological recovery, compared with empty conduits and sensory nerve autografts, at an early time point of regeneration. Keratin hydrogels also produce long-term electrical and histological results superior to empty conduits and equivalent to sensory nerve autografts.