title: A novel internal fixator device for peripheral nerve regeneration.
abstract: Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension--traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA.
authors.forename: Ting-Hsien
authors.initials: TH
authors.lastname: Chuang
authors.forename: Robin E
authors.initials: RE
authors.lastname: Wilson
authors.forename: James M
authors.initials: JM
authors.lastname: Love
authors.forename: John P
authors.initials: JP
authors.lastname: Fisher
authors.forename: Sameer B
authors.initials: SB
authors.lastname: Shah
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D019344:Lactic Acid; D008297:Male; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries / Q000473:pathology* / Q000628:therapy*; D010525:Peripheral Nerves / Q000473:pathology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D044968:Regenerative Medicine / Q000379:methods; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid