Author ORCID Identifier

https://orcid.org/0009-0003-7834-3601

Document Type

Dissertation

Date of Award

2023

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Daniel Engebretson

Abstract

Cardiovascular disease (CVD) is a pressing global health issue with significant socioeconomic consequences. Within the spectrum of CVDs, peripheral artery disease (PAD) and aortic disease necessitate the development of effective and safe treatments. To achieve this, various research models are employed to investigate molecular mechanisms of cells, understand cellular interactions in vascular diseases, assess biocompatibility, and test and evaluate medical devices. This dissertation examines research models and their applications in the advancement of treatments for vascular diseases. For the evaluation of liposome delivery systems in PAD, an ApoE-/- cellular mouse model was employed to investigate the cellular uptake of liposomes compared to wild-type cells, specifically focusing on the preferential uptake by diseased cells. This analysis allowed for a deeper understanding of the targeting capabilities and limitations of liposomal drug delivery in PAD treatment. The dissertation further utilizes a simple vascular benchtop model for the development and optimization of a sirolimus drug coating formulation for drug-coated balloons in PAD treatment. By isolating and simplifying the complexities of the vascular system, the model facilitated the evaluation of the release profile of drug films and dip-coated drug-coated balloons, thereby streamlining the development of the drug delivery system. Swine animal models were used to assess a paclitaxel drug-coated balloon for below-the-knee applications. This model provided a more clinically relevant platform for testing the safety and efficacy of drug-coated balloons. Lastly, the dissertation focuses on the development of a training rehearsal model for aorta stent graft deployment, specifically for thoracoabdominal aortic aneurysm (TAAA) treatment. The study involved end-user interviews to define user needs, conceptualization, design, feasible prototype fabrication, testing, and evaluation. This developing training model has the potential to enhance the proficiency of clinicians in deploying stent-grafts, ultimately improving patient outcomes. In conclusion, this dissertation emphasizes the importance of various research models in investigating vascular disease treatments, providing valuable insights into the development of novel therapies and medical devices for the effective management of cardiovascular diseases. By employing a range of research models, the dissertation contributes to a more comprehensive understanding of vascular model strengths and limitations in the development of therapeutic interventions.

Subject Categories

Analytical, Diagnostic and Therapeutic Techniques and Equipment

Keywords

Cardiovascular Disease, Research Model

Number of Pages

141

Publisher

University of South Dakota

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