title: Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection.
abstract: Bioengineered scaffolds have the potential to support and guide injured axons after spinal cord injury, contributing to neural repair. In previous studies we have reported that templated agarose scaffolds can be fabricated into precise linear arrays and implanted into the partially injured spinal cord, organizing growth and enhancing the distance over which local spinal cord axons and ascending sensory axons extend into a lesion site. However, most human injuries are severe, sparing only thin rims of spinal cord tissue in the margins of a lesion site. Accordingly, in the present study we examined whether template agarose scaffolds seeded with bone marrow stromal cells secreting Brain-Derived Neurotrophic Factor (BDNF) would support regeneration into severe, complete spinal cord transection sites. Moreover, we tested responses of motor axon populations originating from the brainstem. We find that templated agarose scaffolds support motor axon regeneration into a severe spinal cord injury model and organize axons into fascicles of highly linear configuration. BDNF significantly enhances axonal growth. Collectively, these findings support the feasibility of scaffold implantation for enhancing central regeneration after even severe central nervous system injury.
authors.affiliation: Department of Neurosciences, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Gao
authors.forename: Paul
authors.initials: P
authors.lastname: Lu
authors.forename: Bridget
authors.initials: B
authors.lastname: Bednark
authors.forename: Dan
authors.initials: D
authors.lastname: Lynam
authors.forename: James M
authors.initials: JM
authors.lastname: Conner
authors.forename: Jeff
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001672:Biocompatible Materials / Q000737:chemistry; D049108:Cell Enlargement; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005260:Female; D048091:Guided Tissue Regeneration / Q000295:instrumentation*; D054802:Molecular Imprinting / Q000379:methods; D009046:Motor Neurons / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012685:Sepharose / Q000737:chemistry*; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000601:surgery*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D001672:Biocompatible Materials; D012685:Sepharose