title: Robust CNS regeneration after complete spinal cord transection using aligned poly-L-lactic acid microfibers.
abstract: Following spinal cord injury, axons fail to regenerate without exogenous intervention. In this study we report that aligned microfiber-based grafts foster robust regeneration of vascularized CNS tissue. Film, random, and aligned microfiber-based conduits were grafted into a 3 mm thoracic rat spinal cord gap created by complete transection. Over the course of 4 weeks, microtopography presented by aligned or random poly-L-lactic acid microfibers facilitated infiltration of host tissue, and the initial 3 mm gap was closed by endogenous cell populations. This bulk tissue response was composed of regenerating axons accompanied by morphologically aligned astrocytes. Aligned fibers promoted long distance (2055 ± 150 μm), rostrocaudal axonal regeneration, significantly greater than random fiber (1162 ± 87 μm) and film (413 ± 199 μm) controls. Retrograde tracing indicated that regenerating axons originated from propriospinal neurons of the rostral spinal cord, and supraspinal neurons of the reticular formation, red nucleus, raphe and vestibular nuclei. Our findings outline a form of regeneration within the central nervous system that holds important implications for regeneration biology.
authors.affiliation: International Center for Spinal Cord Injury, Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA. hurtado@kennedykrieger.org
authors.forename: Andres
authors.initials: A
authors.lastname: Hurtado
authors.forename: Jared M
authors.initials: JM
authors.lastname: Cregg
authors.forename: Han B
authors.initials: HB
authors.lastname: Wang
authors.forename: Dane F
authors.initials: DF
authors.lastname: Wendell
authors.forename: Martin
authors.initials: M
authors.lastname: Oudega
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Gilbert
authors.forename: John W
authors.initials: JW
authors.lastname: McDonald
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000502:physiology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000737:chemistry*; D016501:Neurites / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy*; D055114:X-Ray Microtomography
chemical_list: D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)