title: Enhanced femoral nerve regeneration after tubulization with a tyrosine-derived polycarbonate terpolymer: effects of protein adsorption and independence of conduit porosity.
abstract: Following complete nerve transection, entubulation of the nerve stumps helps guide axons to reconnect distally. In this study, a biodegradable and noncytotoxic tyrosine-derived polycarbonate terpolymer composed of 89.5 mol% desaminotyrosyl tyrosine ethyl ester (DTE), 10 mol% desaminotyrosyl tyrosine (DT), and 0.5 mol% poly(ethylene glycol) (PEG, molecular weight [Mw]=1 kDa) [designated as E10-0.5(1K)] was used to fabricate conduits for peripheral nerve regeneration. These conduits were evaluated against commercially available nonporous polyethylene (PE) tubes. The two materials are characterized in vitro for differences in surface properties, and the conduits are then evaluated in vivo in a critical-sized nerve defect in the mouse femoral nerve model. Conduits were fabricated from E10-0.5(1K) in both porous [P-E10-0.5(1K)] and nonporous [NP-E10-0.5(1K)] configurations. The results illustrate that adsorption of laminin, fibronectin, and collagen type I was enhanced on E10-0.5(1K) compared to PE. In addition, in vivo the E10-0.5(1K) conduits improved functional recovery over PE conduits, producing regenerated nerves with a fivefold increase in the number of axons, and an eightfold increase in the percentage of myelinated axons. These increases were observed for both P-E10-0.5(1K) and NP-E10-0.5(1K) after 15 weeks. When conduits were removed at 7 or 14 days following implantation, an increase in Schwann cell proteins and fibrin matrix formation was observed in E10-0.5(1K) conduits over PE conduits. These results indicate that E10-0.5(1K) is a pro-regenerative material for peripheral nerves and that the porosity of P-E10-0.5(1K) conduits was inconsequential in this model of nerve injury.
authors.affiliation: 1 New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey , Piscataway, New Jersey.
authors.forename: Mindy
authors.initials: M
authors.lastname: Ezra
authors.forename: Jared
authors.initials: J
authors.lastname: Bushman
authors.forename: David
authors.initials: D
authors.lastname: Shreiber
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Joachim
authors.initials: J
authors.lastname: Kohn
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005267:Femoral Nerve / Q000187:drug effects / Q000502:physiology*; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D011076:Polycarboxylate Cement / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry / Q000494:pharmacology*; D014741:Video Recording
chemical_list: D016326:Extracellular Matrix Proteins; D011076:Polycarboxylate Cement; D011108:Polymers; C005506:polycarbonate; D014443:Tyrosine