Schwann cells in combination with GAG-mimetic scaffolds for spinal cord repair

Author

• Sharareh Hashemi, New Jersey Institute of Technology

Document Type

Dissertation

Date of Award

5-31-2020

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

Treena Livingston Arinzeh

Second Advisor

Stella Elkabes

Third Advisor

Martin Oudega

Fourth Advisor

Bryan J. Pfister

Fifth Advisor

Teresa Wood

Abstract

Spinal cord injury (SCI) being a devastating neurological dysfunction can cause extensive irreversible neuronal loss and axonal damage. Fifty-four cases of spinal cord injury per million people occur annually in the United States. Due to the loss of glial cells and demyelination of axons, the neuronal function of surviving neurons is disrupted leading to permanent loss of sensory and motor functions. The glial scar formed by astrogliosis at the chronic stage protects undamaged tissues, but it is known to be a major barrier for axonal regeneration. The limited regeneration capacity of spinal cord makes it challenging to successfully treat the damaged tissue. To date, there is no effective strategy to completely restore neurological function. An effective treatment must provide a protective and less stressful environment to support and maintain neuronal survival and axonal regeneration, reduce scar formation, and promote remyelination. Neural tissue engineering strategies using biomaterials that more closely mimic the physicochemical properties of native extracellular matrix (ECM) during neural development may be a promising strategy to promote axonal regrowth. During neural development, glycosaminoglycans (GAGs), which are sulfated polysaccharides in the ECM, have been known to play important roles in axonal guidance and growth. Depending upon the degree of sulfation, GAGs can inhibit or promote axonal regeneration. The GAG-mimetic cellulose sulfate (CelS), which can be synthesized to have varying degrees of sulfation, is investigated in this study as a tissue engineering approach to promote axonal regeneration. Aligned oriented fibrous scaffolds containing gelatin blended with CelS are investigated to promote axonal regeneration and extension. CelS with two different degree of sulfation are used in this study, either partially sulfated cellulose (pCleS) with sulfate groups predominantly at the 6-carbon position of the monosaccharide unit and fully sulfated cellulose (fCelS) with sulfate groups predominantly at the 2-, 3-, and 6- carbon positions of the monosaccharide unit. Since native GAGs play an important role in growth factor binding depending on their degree of sulfation, both pCelS and fCelS are investigated for neurotrophic binding. Scaffolds are further evaluated for their potential in promoting neurite extension in the presence of Schwann cells (SCs) and astrocytes. This study demonstrates GAG-mimetic scaffolds are capable of promoting neurite extension with or without SCs. In combination with SCs, they support SC survival, and SC-induced neurite extension and myelination depending upon the degree of sulfation. The GAG-mimetic scaffolds also support neurite extension in the presence of astrocytes without stimulating astrogliosis. This study demonstrates the aligned fibrous GAG-mimetic scaffolds may hold promise for spinal cord repair.

Recommended Citation

Hashemi, Sharareh, "Schwann cells in combination with GAG-mimetic scaffolds for spinal cord repair" (2020). Dissertations. 1872.
https://digitalcommons.njit.edu/dissertations/1872