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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Biomedical Engineering
First Advisor
Mai Lam
Abstract
As the prevalence of cardiovascular diseases continues to rise worldwide, there is a substantial clinical need for vascular grafts to perform bypass and reconstructive surgeries. While autografts and synthetic polymer tubes represent the gold standards for these procedures, issues of limited availability and poor performance in small-diameter (<6mm) applications, respectively, remain unresolved. Tissue engineering has rapidly evolved to fulfill the need for alternative vascular grafts that mimic the native architecture and mechanics of vasculature. Recently, our lab has established a modular technique for fabricating biologically-engineered blood vessels (BEBVs) through cellular self-assembly. This work progressed our technique toward clinical translation by evaluating the use of minimally-invasive autologous cell sources; improving the mechanical integrity of the modular design; and assessing the grafts clinical applicability in vitro. First, adipose-derived mesenchymal stem cells (ASCs) and dermal fibroblasts harvested from patient tissues were assessed as autologous, minimally-invasive surrogates for smooth muscle cells and fibroblasts that reside in the vascular wall. Compared to tissues composed of vascular smooth muscle cells, ASC-based tissues had stiffer mechanical properties due to an increase in the deposition and maturation of collagen. Next, a variety of extracellular matrix hydrogels were examined as an exterior coating to improve the integration of modular tissue rings into vessels. Despite having the weakest mechanical properties as a material alone, fibroblast-embedded fibrin hydrogels supported cell viability and had the highest ultimate tensile strength as an exterior vascular coating following 2 weeks of culture in vitro. Lastly, tissue engineered vessels were examined for clinical applicability in vitro through burst pressure testing, suturability, as well as, endothelial cell and platelet compatibility. The developed BEBVs had an average burst pressure of 229 ± 23.8 mmHg and were successfully sutured to the abdominal aorta of a rabbit demonstrating their readiness for future short-term hemocompatibility studies in vivo.
Recommended Citation
Wonski, Bryan Thomas, "Development Of Biologically-Engineered Blood Vessels Towards Clinical Translation" (2023). Wayne State University Dissertations. 3916.
https://digitalcommons.wayne.edu/oa_dissertations/3916