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Local Delivery of Polycations from a Hydrogel Scaffold for Treating Spinal Cord Injury

Thursday, July 21, 2022

10:00 AM-12:00 PM

BIOMED Master's Thesis Defense

Local Delivery of Polycations From a Hydrogel Scaffold for Treating Spinal Cord Injury

Gillian Carver, Master's Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Yinghui Zhong, PhD
Associate Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Spinal cord injury (SCI) is a severe condition with life altering function consequences. The approximately 17,000 new patients that suffer from SCI each year undergo a primary injury that causes SCI, then experience secondary injury as part of the body’s response to isolate the damaged area from healthy neurons, forming a glial scar. Although isolation of the injury site is important to protect surrounding neurons, secondary injury typically enlarges the area of injury and prevents recovery after SCI by creating a physical and chemical barrier through which healthy neurons cannot grow. Therefore, there is a need for a biomaterial that can encourage neuron growth past the glial scar and support neuron growth into the injury site. Agarose is a commonly used biomaterial for neural tissue engineering since it is mechanically similar to neurons and is a relatively inert biomaterial. Two polycations, chitosan and protamine, are investigated here for release from agarose hydrogels to promote neuron growth over inhibitory CSPGs, a common inhibitory molecule in the glial scar. Chitosan promotes neuron growth across CSPGs at a low dose but is toxic at higher dosages. Thiolated chitosan avoids the toxic effects of unmodified chitosan and promotes neuron growth across CSPGs for a wider range of dosages. Protamine is ineffective at low dosages and toxic at high dosages.

The original biomaterial design involved incorporation of a polyanion into the gel, but was discarded after it was found that polyanion was not immobilized in the gel and released at a greater quantity than the positive molecule. Subsequent experiments determined that protamine release was only tunable through increasing the temperature at which the agarose stock solution was dissolved. Chitosan release was tunable through increasing the dissolution temperature of agarose stock, increasing the relative agarose-drug concentration, modifying the drug and the agarose with reactive groups, and by increasing the molecular weight of the chitosan. Overall, a biomaterial that meets the drug release criteria can be fabricated by increasing the molecular weight of thiolated chitosan and incorporating this modified chitosan into an agarose hydrogel modified with divinylsulfone groups.

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