Integrative Tissue Engineering in the Spinal Cord

Mayo Clinic, Rochester MN

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Abstract

DESCRIPTION (provided by applicant): An integrative, tissue-engineering approach to treat spinal cord injury will be evaluated in a rat transection model. A biodegradable implant with controlled microarchitecture will be developed and fabricated from poly(lactic-co-glycolic acid) (PLGA). Implant architecture will be evaluated and characterized with scanning electron microscopy, confocal microscopy, and X-ray micro-computed tomography. Chondroitinase ABC (C-ABC), an enzyme shown to break down the proteoglycan-rich scar that results from injury, will be encapsulated in PLGA microspheres, and its bioactivity and release kinetics will be evaluated in vitro. Techniques for incorporating C-ABC into the polymer implant will be investigated, and the distribution and release of C-ABC from the implant will be described. Schwann cells will be harvested from neonatal rat pup sciatic nerves, expanded in cell culture, and suspended in Matrigel for incorporation into the polymer implant. Adult Sprague-Dawley rats will be anesthetized before receiving thoracic 8-9 laminectomies and spinal cord transections. Various implants will be inserted into the spinal canals and the dura closed over them. Spinal cords will be harvested at multiple time points, split longitudinally, and fixed for histology, immunohistochemistry, and scanning electron microscopy (SEM). Morphologic evaluation of tissue repair will be performed on tissue sections, while functional assays will be employed for assessment of neurological recovery. Experimental groups and controls will be evaluated for determining the effects of each implant component, as well as their various combinations, on axon regeneration and functional recovery.