Date of Award

2024-08-01

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

Advisor(s)

Sylvia Natividad-Diaz

Abstract

According to the American Heart Association and World Health Organization, cardiovascular diseases (CVDs) are the leading cause of death worldwide. Monolayer cell culture (2D) and animal models are conventional methods to study CVDs, however, they limit researcherâ??s ability to simulate the human cardiovascular cellular microenvironments and accurate predication of pharmaceutical drug responses. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), biomaterials, and microfluidic technologies can be combined to create a controlled, reproducible 3D platform to study physiologically-relevant cellular responses to biochemical and physical changes in the microenvironment. My dissertation work demonstrates the development of novel self-driven microfluidic devices designed with capillary action fluid flow principles that can be fabricated with 3D Stereolithography (SLA) printing and polymer casting methods. The integration of 3D cardiovascular tissue models within these microfluidic devices allowed for the evaluation of cell organization, function, and responses to biochemical and physical changes within the system. This work is significant because the 3D cardiovascular tissue models demonstrated differences in cellular morphology and structural reorganization in devices with or without microposts up to 5 days in culture relative to standard culture methods. Multiple cell types were cultured in 3D within the microfluidic devices, including human umbilical vein endothelial cells (HUVECs), human AC16 cardiomyocytes, hiPSC-CMs, SKBR3 breast cancer cells, and patient derived xenograft (PDX) breast cancer cells, demonstrating the versality of the microfluidic devices. Furthermore, the microfluidic device was integrated into two specific technology applications (TA), including a cardiovascular-breast cancer tissue model (TA-1) and cardiovascular model in simulated microgravity (TA-2). The TA-1 results indicate hiPSC-CMs are susceptible to reduced viability when treated with Herceptin, a HER2+ breast cancer chemotherapy drug. The TA-2 results demonstrated hiPSC-CMs cultured in microgravity maintained their phenotype relative to control studies in standard culture conditions. This work provides significant advancements in the design, fabrication, and study of capillary-driven microfluidic devices and their use as a platform for CVD research in multiple areas of biotechnology research.

Language

en

Provenance

Received from ProQuest

File Size

141 p.

File Format

application/pdf

Rights Holder

Aibhlin Alexis Esparza

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Included in

Biomedical Commons

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