Date of Award

5-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering and Sciences

First Advisor

Christopher A. Bashur

Second Advisor

Vipuil Kishore

Third Advisor

Yi Liao

Fourth Advisor

Venkat Keshav Chivukula

Abstract

Endothelial cells (ECs) are vital for maintaining proper vascular function and regulating processes such as hemostasis and inflammation. Disruption of endothelial cells integrity can lead to several pathological conditions, including coronary artery disease, vascular cognitive impairment, and dementia (VCID). Alterations in ECs distribution may lead to compromised blood-brain barrier (BBB) function, facilitating the passage of blood components and contributing to conditions such as Alzheimer's disease. Additionally, disruptions in ECs function can lead to early-stage thrombosis and intimal hyperplasia, resulting in graft failure in small-diameter (

This study aimed to develop innovative approaches for drug delivery to the BBB and TEVGs to improve endothelialization and mitigate associated risks. To this end, microbubbles (MBs) and electrospun-based constructs were employed to deliver active compounds. MBs were engineered using perfluorocarbon (PFC) to transport carbon monoxide and restore endothelial cells at the BBB in vitro. Furthermore, fibrin-coated polycaprolactone (PCL) constructs were utilized to deliver the UPI peptide and enhance endothelialization in proposed TEVGs, both in vitro and in vivo. Additional modifications were implemented to optimize the release profile of the UPI peptide and evaluate its specificity for endothelialization. The findings of this study suggest that these novel techniques hold promise for improving endothelialization at targeted sites

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