title: Chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel promote peripheral nerve regeneration in rats.
abstract: Treating peripheral nerve defects represents a clinical challenge, and nerve conduits lacking an internal scaffold lead to limited large nerve gap regeneration. Here, we bridged 10-mm sciatic nerve defects in rats with a chitosan conduit filled with 0, 0.5, or 1.0 mg of simvastatin in Pluronic F-127 hydrogel. We assessed subsequent nerve regeneration using the sciatic functional index (SFI), electrophysiological assessments, Fluoro-Gold (FG) retrograde tracing, gastrocnemius muscle mass measurements, and histological and immunohistochemical assessments of nerve regeneration. Ten weeks after implantation, the chitosan conduit filled with simvastatin/Pluronic F-127 hydrogel promoted nerve regeneration; there were significant increases in the SFI, compound muscle action potential peak amplitude, motor nerve conduction velocity, FG-labeled neuron number in the dorsal root ganglia, myelin sheath thickness, axon diameter, gastrocnemius wet weight, and muscle fiber area percentage in the gastrocnemius muscle (all p < 0.05). The expression levels of neurotrophic factors, such as pleiotrophin, hepatocyte growth factor, vascular endothelial growth factor, and glial cell line-derived neurotrophic factor, were also found to be increased. The results suggest that chitosan conduits filled with simvastatin/Pluronic F-127 hydrogel improved peripheral nerve regeneration and functional recovery in rats, which may have been related to the increased expression of several endogenous neurotrophic factors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 787-799, 2018.
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Hai
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.affiliation: Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, 100191, China.
authors.forename: Yingsheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Beijing, 100191, China.|Beijing Key Laboratory of Spinal Diseases, Beijing, 100191, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Song
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D020442:Poloxamer / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology*; D019821:Simvastatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D020100:Hydrogels; D020442:Poloxamer; D048271:Chitosan; D019821:Simvastatin
keywords: Pluronic F-127 hydrogel; chitosan conduit; endogenous neurotrophic factors; peripheral nerve injury; simvastatin