title: Relationship between scaffold channel diameter and number of regenerating axons in the transected rat spinal cord.
abstract: Regeneration of endogenous axons through a Schwann cell (SC)-seeded scaffold implant has been demonstrated in the transected rat spinal cord. The formation of a cellular lining in the scaffold channel may limit the degree of axonal regeneration. Spinal cords of adult rats were transected and implanted with the SC-loaded polylactic co-glycollic acid (PLGA) scaffold implants containing seven parallel-aligned channels, either 450mum (n=19) or 660microm in diameter (n=14). Animals were sacrificed after 1, 2 and 3months. Immunohistochemistry for neurofilament expression was performed. The cross-sectional area of fibrous tissue and regenerative core was calculated. We found that the 450microm scaffolds had significantly greater axon fibers per channel at the 1month (186+/-37) and 3month (78+/-11) endpoints than the 660microm scaffolds (90+/-19 and 40+/-6, respectively) (p=0.0164 and 0.0149, respectively). The difference in the area of fibrous rim between the 450 and 660microm channels was most pronounced at the 1month endpoint, at 28,046+/-6551 and 58,633+/-7063microm(2), respectively (p=0.0105). Our study suggests that fabricating scaffolds with smaller diameter channels promotes greater regeneration over larger diameter channels. Axonal regeneration was reduced in the larger channels due to the generation of a large fibrous rim. Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Krych
authors.forename: Gemma E
authors.initials: GE
authors.lastname: Rooney
authors.forename: Bingkun
authors.initials: B
authors.lastname: Chen
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Schermerhorn
authors.forename: Syed
authors.initials: S
authors.lastname: Ameenuddin
authors.forename: LouAnn
authors.initials: L
authors.lastname: Gross
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Bradford L
authors.initials: BL
authors.lastname: Currier
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Spinner
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Friedman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology*; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D019544:Equipment Failure Analysis; D048091:Guided Tissue Regeneration / Q000295:instrumentation* / Q000379:methods; D009416:Nerve Regeneration / Q000502:physiology*; D019736:Prostheses and Implants; D011474:Prosthesis Design; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000473:pathology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000601:surgery*; D016896:Treatment Outcome