title: Repair of peripheral nerve defects in rabbits using keratin hydrogel scaffolds.
abstract: Entubulation of transected nerves using bioabsorbable conduits is a promising alternative to sural nerve autografting, but full functional recovery is rarely achieved. Numerous studies have suggested that scaffold-based conduit fillers may promote axon regeneration, but no neuroinductive biomaterial filler has been identified. We previously showed that a nerve guide filled with keratin hydrogel actively stimulates regeneration in a mouse model, and results in functional outcomes superior to empty conduits at early time points. The goal of the present study was to develop a peripheral nerve defect model in a rabbit and assess the effectiveness of a keratin hydrogel filler. Although repairs with keratin-filled conduits were not as consistently successful as autograft overall, the use of keratin resulted in a significant improvement in conduction delay compared to both empty conduits and autograft, as well as a significant improvement in amplitude recovery compared to empty conduits when measurable regeneration did occur. Taking into account all study animals (i.e., regenerated and nonregenerated), histological assessment showed that keratin-treated nerves had significantly greater myelin thickness than empty conduits. These data support the findings of our earlier study and suggest that keratin hydrogel fillers have the potential to be used clinically to improve conduit repair.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA.
authors.forename: Paulina S
authors.initials: PS
authors.lastname: Hill
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Apel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barnwell
authors.forename: Tom
authors.initials: T
authors.lastname: Smith
authors.forename: L Andrew
authors.initials: LA
authors.lastname: Koman
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Mark
authors.initials: M
authors.lastname: Van Dyke
mesh_terms: D000818:Animals; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena / Q000187:drug effects; D048091:Guided Tissue Regeneration; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007633:Keratins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D011817:Rabbits; D020127:Recovery of Function / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007633:Keratins; D003094:Collagen