title: Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts.
abstract: Despite spontaneous sprouting of peripheral axons after transection injury, peripheral regeneration is incomplete and limited to short gaps, even with the use of autograft tissue, which is considered to be the "gold" standard. In an attempt to obviate some of the problems associated with autografts, including limited donor tissue and donor site morbidity, we aimed to synthesize a synthetic nerve guidance channel that would perform as well as the nerve autograft. Given that the patency of the nerve guidance channel is critical for repair, we investigated a series of nerve guidance channel designs where patency and the resulting regenerative capacity were compared in a transected rat sciatic nerve injury model. Three tube designs were compared to autograft tissue: plain, corrugated and coil-reinforced tubes of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate). Of the three designs, the coil-reinforced tubes demonstrated superior performance in terms of patency. By electrophysiology and histomorphometry, the coil-reinforced tubes demonstrated outcomes that were comparable to autografts after both 8 and 16 weeks of implantation. The nerve action potential (NAP) velocity and muscle action potential (MAP) velocity for the coil-reinforced PHEMA-MMA tube was 54.6+/-10.1 and 10.9+/-1.3 m/s, respectively at 16 weeks, which was statistically equivalent to those of the autograft at 37.5+/-7.9 and 11.3+/-2.0 m/s. The axon density in the coil-reinforced tube was 2.16+/-0.61x10(4) axons/mm2, which was statistically similar to that of the autograft of 2.41+/-0.62x10(4) axons/mm2 at 16 weeks. These coil-reinforced tubes demonstrated equivalence to autografts for nerve regeneration, demonstrating the importance of channel design to regenerative capacity and more specifically the impact of patency to regeneration.
authors.affiliation: matREGEN Corporation, 200 College Street, Suite 28, Toronto, Ont., Canada M5S 3E5.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Katayama
authors.forename: Rivelino
authors.initials: R
authors.lastname: Montenegro
authors.forename: Thomas
authors.initials: T
authors.lastname: Freier
authors.forename: Rajiv
authors.initials: R
authors.lastname: Midha
authors.forename: Jason S
authors.initials: JS
authors.lastname: Belkas
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000473:pathology; D003094:Collagen / Q000737:chemistry; D019245:Compressive Strength; D003692:Delayed-Action Preparations / Q000737:chemistry; D004594:Electrophysiology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology / Q000627:therapeutic use; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods*; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use*; D020007:Implants, Experimental; D008297:Male; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects*; D009417:Nerve Tissue / Q000637:transplantation*; D011102:Polyhydroxyethyl Methacrylate / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000293:injuries / Q000503:physiopathology*; D014182:Transplantation, Autologous
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D008689:Methacrylates; D016220:Fibroblast Growth Factor 1; D011102:Polyhydroxyethyl Methacrylate; C059480:poly(hydroxyethyl methacrylate-methacrylic acid)hydrogel; D003094:Collagen