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DELAYED IMPLANTATION OF INTRAMEDULLARY CHITOSAN CHANNELS CONTAINING NERVE GRAFTS PROMOTES EXTENSIVE AXONAL REGENERATION AFTER SPINAL CORD INJURY

Nomura, Hiroshi M.D., Ph.D.; Baladie, Bilal Ph.D.; Katayama, Yusuke M.A.Sc.; Morshead, Cindi M. Ph.D.; Shoichet, Molly S. Ph.D.; Tator, Charles H. M.D., Ph.D.

doi: 10.1227/01.NEU.0000316443.88403.16
Experimental Studies

OBJECTIVE: We describe a new strategy to promote axonal regeneration after subacute or chronic spinal cord injury consisting of intramedullary implantation of chitosan guidance channels containing peripheral nerve (PN) grafts.

METHODS: Chitosan channels filled with PN grafts harvested from green fluorescent protein rats were implanted in the cavity 1 week (subacute) or 4 weeks (chronic) after 50-g clip injury at T8 and were compared with similarly injured animals implanted with either unfilled channels or no channels. Functional recovery was measured weekly for 12 weeks by open-field locomotion, after which histological examination was performed.

RESULTS: The implanted channels with PN grafts contained a thick tissue bridge containing as many as 35,000 myelinated axons in both the subacute and chronic spinal cord injury groups, with the greatest number of axons in the channels containing PN grafts implanted subacutely. There were numerous green fluorescent protein-positive donor Schwann cells in the tissue bridges in all animals with PN grafts. Moreover, these Schwann cells had high functional capacity in terms of myelination of the axons in the channels. In addition, PN-filled chitosan channels showed excellent biocompatibility with the adjacent neural tissue and no obvious signs of degradation and minimal tissue reaction at 14 weeks after implantation. In control animals that had unfilled chitosan channels implanted, there was minimal axonal regeneration in the channels; in control animals without channels, there were large cavities in the spinal cords, and the bridges contained only a small number of axons and Schwann cells. Despite the large numbers of axons in the chitosan channel–PN graft group, there was no significant difference in functional recovery between treatment and control groups.

CONCLUSION: Intramedullary implantation of chitosan guidance channels containing PN grafts in the cavity after subacute spinal cord injury resulted in a thicker bridge containing a larger number of myelinated axons compared with chitosan channels alone. A chitosan channel containing PN grafts is a promising strategy for spinal cord repair.

Toronto Western Research Institute, Toronto Western Hospital, Toronto, Canada (Nomura)

Department of Chemical Engineering and Applied Chemistry, University of Toronto, and Department of Chemistry, Institute of Biomaterials and Biomedical Engineering, Toronto, Canada (Baladie)

matREGEN, Toronto, Canada (Katayama)

Department of Surgery and Institute of Medical Sciences, University of Toronto, and Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, Canada (Morshead)

Department of Chemical Engineering and Applied Chemistry, University of Toronto, and Department of Chemistry, Institute of Biomaterials and Biomedical Engineering, Terrence Donnelly Centre for Cellular and Biomolecular Research, Toronto, Canada (Shoichet)

Toronto Western Research Institute, Toronto Western Hospital and University of Toronto, Toronto, Canada (Tator)

Reprint requests: Charles H. Tator, M.D., Ph.D., Toronto Western Research Institute, Toronto Western Hospital and University of Toronto, Room 12-435, McLaughlin Wing, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. Email: charles.tator@uhn.on.ca

Received, October 19, 2007.

Accepted, March 10, 2008.

Copyright © by the Congress of Neurological Surgeons