Defense Date

11-9-2021

Graduation Date

Fall 12-19-2021

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

Committee Chair

Ellen S. Gawalt

Committee Member

Michael Van Stipdonk

Committee Member

Jeffrey Evanseck

Committee Member

Wilson Meng

Keywords

Self-assembled monolayers, corrosion, Ticagrelor, thrombosis, vascular stent

Abstract

Percutaneous coronary interventions are a widely used cardiovascular surgery which is typically accompanied by the insertion of a vascular stent. After the procedure patients are put on dual anti-platelet therapy (DAPT) to prevent stent thrombosis, a common complication to this procedure in which platelets aggregate in the blood vessel on the inserted stent. Systemic deactivation of platelets in patients via oral DAPT results in patients becoming bleeding risks in future medical procedures, necessitating the development of a localized delivery system for anti-platelet medications from the surface of the stent. A novel anti-thrombogenic vascular stent coating has been prepared by covalent linking of Ticagrelor onto the surface of low carbon stainless steel grade 316L (SS316L) and Cobalt Chromium L605 (CoCr). The surface of stents were functionalized with an amine terminated self-assembled monolayer (SAM). The functionalized surface was modified via the Mitsunobu reaction, forming a covalent secondary amine linkage between the molecules in the monolayer and Ticagrelor. Surface characterization by diffuse reflectance infrared spectroscopy confirmed the presence of TIC on the surface. Atomic force microscopy and contact angle goniometry established significant chemical changes to the surface post-reaction, consistent with surface immobilization. Following analytical characterization, protection against thrombus formation was evaluated using platelet rich plasma and scanning electron microscopy, an ELISA assay, and flow cytometry. Platelets did not adhere to the modified substrates and platelet inhibition was localized to the surface so that platelet activation was not inhibited in a systemic manner.

Language

English

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