title: The use of keratin biomaterials derived from human hair for the promotion of rapid regeneration of peripheral nerves.
abstract: The management of trauma-associated nerve defects is difficult because of the absence of autologous donor motor or sensory nerves. Pre-clinical development and clinical experience has shown that damaged nerves can be surgically repaired using a tubular conduit interposed across the defect. Acceptable patient outcomes are achieved so long as the gap distance does not exceed a few centimeters. Although research in animals has demonstrated that nerve repair can be facilitated across slightly larger gaps by introducing a biomaterial filler into the conduit lumen, these biomaterials are not typically "neuroinductive" (i.e. capable of acting directly on regenerative cells to enhance nerve tissue formation beyond clinical limits). Moreover, their use does not often result in functional recovery equivalent to nerve autograft, the clinical gold standard. Here we show that a biomaterial gel made from the proteins found in human hair can mediate a robust nerve regeneration response, in part through activation of Schwann cells. In vitro, keratins extracted from human hair enhance the activity of Schwann cells by a chemotactic mechanism, increase their attachment and proliferation, and up-regulate expression of important genes. Moreover, these characteristics translate to improved functional nerve recovery in an animal model. These results suggest that a biomaterial derived from human hair keratins is neuroinductive and can facilitate an outcome comparable to autograft in a nerve injury model.
authors.affiliation: The Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sierpinski
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Garrett
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ma
authors.forename: Peter
authors.initials: P
authors.lastname: Apel
authors.forename: David
authors.initials: D
authors.lastname: Klorig
authors.forename: Thomas
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; D001672:Biocompatible Materials / Q000494:pharmacology*; D002460:Cell Line; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006197:Hair / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels; D007633:Keratins / Q000302:isolation & purification / Q000494:pharmacology* / Q000648:ultrastructure; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D010525:Peripheral Nerves / Q000098:blood supply / Q000187:drug effects* / Q000254:growth & development; D016062:Porosity; D051381:Rats; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D007633:Keratins