title: Long-term characterization of axon regeneration and matrix changes using multiple channel bridges for spinal cord regeneration.
abstract: Spinal cord injury (SCI) results in loss of sensory and motor function below the level of injury and has limited available therapies. The host response to SCI is typified by limited endogenous repair, and biomaterial bridges offer the potential to alter the microenvironment to promote regeneration. Porous multiple channel bridges implanted into the injury provide stability to limit secondary damage and support cell infiltration that limits cavity formation. At the same time, the channels provide a path that physically directs axon growth across the injury. Using a rat spinal cord hemisection injury model, we investigated the dynamics of axon growth, myelination, and scar formation within and around the bridge in vivo for 6 months, at which time the bridge has fully degraded. Axons grew into and through the channels, and the density increased overtime, resulting in the greatest axon density at 6 months postimplantation, despite complete degradation of the bridge by that time point. Furthermore, the persistence of these axons contrasts with reports of axonal dieback in other models and is consistent with axon stability resulting from some degree of connectivity. Immunostaining of axons revealed both motor and sensory origins of the axons found in the channels of the bridge. Extensive myelination was observed throughout the bridge at 6 months, with centrally located and peripheral channels seemingly myelinated by oligodendrocytes and Schwann cells, respectively. Chondroitin sulfate proteoglycan deposition was restricted to the edges of the bridge, was greatest at 1 week, and significantly decreased by 6 weeks. The dynamics of collagen I and IV, laminin, and fibronectin deposition varied with time. These studies demonstrate that the bridge structure can support substantial long-term axon growth and myelination with limited scar formation.
authors.affiliation: 1 Department of Chemical and Biological Engineering, Northwestern University , Evanston, Illinois.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Tuinstra
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Margul
authors.forename: Ashley G
authors.initials: AG
authors.lastname: Goodman
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Boehler
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Holland
authors.forename: Marina L
authors.initials: ML
authors.lastname: Zelivyanskaya
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cummings
authors.forename: Aileen J
authors.initials: AJ
authors.lastname: Anderson
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000473:pathology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D058630:Spinal Cord Regeneration; D013997:Time Factors
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D005353:Fibronectins; D007797:Laminin; D002809:Chondroitin Sulfates; D000110:Acetylcholinesterase; D015740:Calcitonin Gene-Related Peptide