Design and Optimization of a Blood Vessel Mimic Bioreactor System for the Evaluation of Intravascular Devices in Simple and Complex Vessel Geometries

Abstract

Coronary artery disease affects millions of people and the ability to detect and treat the disease is advancing at a rapid rate. As a result, the development of intravascular technologies is the focus of many medical device manufacturers. Specifically, coronary stent implantation is being performed in an increasing number of patients and a number of new stent designs have been introduced to the market, resulting in the need for improved preclinical testing methods. An in vitro tissue engineered "blood vessel mimic" (BVM) system has previously been established and its feasibility for the initial testing of newly emerging intravascular technology has been demonstrated. There are limitations that exist with this original design, however, and the focus of this thesis was to both improve and expand upon the original model. Therefore, research was conducted based on two specific aims. The first aim was to develop a more ideal BVM system to accommodate a wider range of stent lengths and diameters, while allowing for easy graft insertion and seal-ability. The second aim was to develop next generation BVM systems, v focused on future needs and technology, such as long, angulated and bifurcated geometries.The work described in this thesis demonstrates that a BVM chamber can be created which has the advantages of easy graft insertion and seal-ability, as well as the ability to accommodate varying sizes of vessel scaffolds, all while maintaining the needs of a tissue engineering bioreactor system. The next generation BVM systems presented demonstrate that the BVM concept can be expanded to meet the needs of long, angulated and bifurcated geometries. Overall, the work in this thesis describes the design and optimization of an in vitro blood vessel mimic bioreactor system for the evaluation of intravascular devices, specifically coronary stents, in simple and complex vessel geometries.vi ACKNOWLEDGEMENTS First, I would like to acknowledge and thank the members of my thesis committee: Dr. Kristen O'Halloran Cardinal, Dr. Trevor Cardinal and Dr. Lily Laiho. Thanks for all your guidance and input and for providing assistance and ideas throughout the project.

Tissue-engineered blood vessel mimics in complex geometries for intravascular device testing

“…Ultimately, multifunctional bioreactors were designed and constructed to support multiple BVM geometries. More detailed parts lists and assembly instructions are available [19,20].…”

Development of In Vitro Tissue Engineered Blood Vessel Mimics in Complex Geometries for Coronary Stent Testing

“…Because the ePTFE scaffold currently used to develop straight BVMs is flexible, previous designs proposed that straight ePTFE scaffolds simply be bent into coronary geometries. To mimic the specific coronary bends defined by the American College of Cardiology and the American Heart Association, previous designs proposed three geometries for bent scaffolds: a scaffold bent less than 45 degrees, a scaffold bent 90 degrees, and a scaffold bent 180 degrees [71]. Some coronary bifurcations observed in clinical practice are T-shaped [73], and previous designs proposed that two straight ePTFE scaffolds be sutured together in a T-shape to mimic a T-shaped coronary bifurcation ( Figure 2.3 A).…”

The Characterization of Biofilm Attachment to Metal Interfaces: Effects of Substratum Properties

“…A section of the flow tube is incorporated through an external pulsatile pump in order to create flow in the system, and a media reservoir was added in order to keep the media levels high and prevent air bubbles travelling through the system. Also, there are several valves and stop cocks used to control the flow through the bioreactor (Leifer 2008). This system can be used to seed and culture Human Umbilical Vein Endothelial Cells (HUVECs), which are very complex eukaryotic cells.…”