title: Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.
abstract: Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.
authors.affiliation: 1] Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland [2] Department of Biological Sciences, Wichita State University, Wichita, KS, USA.
authors.forename: L
authors.initials: L
authors.lastname: Yao
authors.forename: W
authors.initials: W
authors.lastname: Daly
authors.forename: B
authors.initials: B
authors.lastname: Newland
authors.forename: S
authors.initials: S
authors.lastname: Yao
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: B K K
authors.initials: BK
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Madigan
authors.forename: A
authors.initials: A
authors.lastname: Windebank
authors.forename: A
authors.identifier: 0000000262924933
authors.initials: A
authors.lastname: Pandit
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D003094:Collagen; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D017628:Microglia / Q000502:physiology; D009416:Nerve Regeneration; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D054457:Tissue Scaffolds
chemical_list: D020933:Neurotrophin 3; D003094:Collagen