Advisory Committee Chair
Advisory Committee Members
Brigitta C Brott
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Engineering
While cardiovascular stent technology has considerable advances, there are hurdles to overcome due to the dysfunctional stented arteries which fail to maintain vascular homeostasis. Current stent designs ignored the significance of promoting functional artery healing (pro-healing). Therefore, we developed a pro-healing nanomatrix coating for stent. Previous studies investigated its effect on individual vascular cell type. In natural artery, there are multiple vascular cell types that strongly affect stent performance. Thus, an in vitro vascular double-layer (VDL) system was used to observe stent effects on different vascular cell types. And the pro-healing ability and mechanism of the nanomatrix coated stent were studied in the VDL and a rabbit model, compared to commercial bare metal stent (BMS) and drug eluting stent (DES). In vitro results indicated that this stent coating could 1) improve endothelialization and endothelial functions, 2) regulate smooth muscle cell phenotype to reduce the proliferation and migration, 3) suppress inflammation through a multifactorial manner, and 4) reduce foam cell formation, extracellular matrix remodeling, and calcification. Consistently, in vivo results demonstrated that compared with commercial BMS and DES, this pro-healing nanomatrix coated stent enhanced reendothelialization with negligible restenosis, inflammation, or thrombosis. Thus, these findings indicate the unique pro-healing feature of this nanomatrix stent coating with superior efficacy. On the other side, in vitro atherosclerosis models are essential to evaluate vascular stent and therapeutics before in vivo and clinical studies, but significant limitations remain, such as the lack of three-layer vascular architecture and limited atherosclerotic features. Moreover, no scalable 3D atherosclerosis model is available for making high-throughput therapeutic evaluation. Herein, an in vitro 3D three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features (VSA) was developed with endothelial dysfunction, monocyte recruitment, macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells, and calcification initiation. Notably, a high-throughput functional VSA assay was created and the use of these assays for evaluating atherosclerosis therapeutics was also performed including conventional drugs, therapeutic candidates, and a potential gene therapy. It demonstrated that VSA is a valuable in vitro platform for vascular therapeutics and device evaluation with high efficiency and flexibility.
Zhang, Xixi, "Development and Evaluation of a Nanomatrix Coated Stent Using a Vascular Sheet With Atherosclerosis Model" (2023). All ETDs from UAB. 23.