Transform Off-the-Shelf Synthetic Grafts to Autologous Conduits for Coronary Artery Bypass Grafting
Abstract
Coronary arterial disease is the leading cause of death in the United States in both women and men. Arterial disease of the heart alone costs well over $2.5B for the Department of Veterans Affairs (VA) system alone. Current coronary artery bypass grafting requires harvesting of the patient’s own vessels as grafts. Veterans and Service members frequently suffer from comorbidities such as diabetes, which increases the risks of conduit harvesting. Further, limb amputation and chest trauma related to military service rob Veterans of these common sources of grafts for use during coronary bypass operations. As such, certain Veterans cannot even receive this routine lifesaving procedure. In fact, up to one-third of patients lack appropriate grafts during bypass grafting. To meet this challenge, we design grafts made of rubbers and plastics that are designed and patented specifically for vascular grafts. Unlike current grafts on the market or in clinical trials, the patients’ own body will change our grafts over time to their own vessels. This is demonstrated in rat aorta and carotid arteries. Existing grafts cannot even be used in arteries less than 6 mm in diameter. Our approach eliminates cell harvesting surgeries and avoids long cell-culture time associated with traditional tissue engineering strategies. In rat models, which have the same blood pressure as human, our synthetic grafts transform into host vessels. These neo-vessels are populated by the same kind of cells and the same types of molecules external to the cells as native vessels. In a 3-month follow-up study in rat carotid arteries, the synthetic graft performs similarly to the vein graft harvested from the same animal. The two aims of this project will finalize graft design parameters and test the grafts in a pig coronary artery bypass grafting model. Specific Aim 1: Finalize graft fabrication methodology and select the best design using a rat carotid artery model. Our graft is composed of an elastic porous inner tube and a robust sheath. Studies to date indicate that the inner tube performs well. This project will finalize the design of sheath material and the sheath fiber diameter. To select the best design for the pig study, we will use male and female adult rats to examine the graft in carotid arteries: a small diameter artery subjected to bending and twisting. We will compare the remodeled grafts with adjacent arteries, and the unoperated arteries on the other side of the neck. We will examine the function of the cells within the grafts, the type of molecules made by the cells, the mechanical properties, and the architecture of the tissue to gain a holistic view on the transition from a synthetic graft to a biological vessel. Specific Aim 2: Evaluate the performance of the selected grafts in a pig coronary artery bypass grafting model. Pig is one of the best models for human in bypass grafting. We will make pig-sized grafts of the best performing design in Aim 1. We will implant the grafts to bypass the closed coronary artery in the pig heart. We will examine how well blood flows in the grafts, how strong and elastic are the grafts, and how cells are organized in the grafts during the 6-month follow-up. Dr. Green has performed thousands of coronary artery bypass grafting procedures in civilian and Veteran patient populations. We appreciate the challenges associated with our project, and our study to date indicates that our graft design will meet these challenges. When successfully implemented, the impact of this project is well beyond coronary artery bypass grafting. This technology will transform reconstructive procedures and replantations of amputated tissues. This technology will similarly offer robust hemodialysis access grafts for kidney failure patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910298
Entities
People
- Randall Green
Organizations
- State University of New York Upstate Medical University
- United States Army