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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 T. Lam

Abstract

This body of work sets to investigate the layer specific effects of balloon angioplasty in a bilayer tissue engineering model. By investigating the media and adventitia, we may draw conclusions about the implications on mechanical and subsequent cellular effects from balloon angioplasty inflation times. Tissue engineering provides a unique opportunity to develop disease models with simplicity and controllability to show individual or combined contributions of biological make up and mechanical properties of human vasculature. Here a bilayer tissue engineering model was created using the Ring Stacking Method (RSM). In the RSM cells are seeded on fibrin hydrogel in a plate containing a concentrically placed post and over the course of several days the monolayer of cells self-assembles into a ring. Rings are then stacked and adhered to one another using fibrin glue to create a vessel. To create the bilayer model, the RSM method was adapted to create an adventitia using human dermal fibroblast cells. To achieve sufficient strength, a variety of methods were tested including cytokine stimulations to elicit collagen production, hydrogel modifications to include collagen gel, and incorporation of decellularized dermal matrix into the ring formation process. Bilayer tissues were created by adapting the ring formation process to first form the media ring using human aortic smooth muscle cells followed by creating a surrounding adventitia ring. These bilayer tissues were subjected to balloon angioplasty inflation times of 1- and 5- minutes. Tissues were immediately tensile tested following balloon angioplasty, in which mechanical changes were observed in the media with significant effects following inflation of 5 minutes. No mechanical change was observed in the adventitia irrespective of inflation time. Long term culture of tissues following inflation indicated increasing inflation times reduced contractile phenotype of smooth muscle cells with diminished contractile protein expression and increased mature collagen presence. Together, this work shows the successful creation of a bilayer tissue engineering model used to study the layer specific effects of balloon angioplasty.

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