Date of Award
Master of Science (MS)
Dr. Dan Simonescu, Committee Chair
Dr. Agneta Simionescu
Dr. Martine LaBerge
In the United States, 1 out of every 9 death certificates in 2013 referenced heart failure.1 Despite the outstanding need of treatment options for heart failure, heart transplantation remains the optimal treatment method. However, there is a severe shortage of donor hearts available for transplantation.2 Other available treatment options are not ideal because they do not fully restore function and are associated with creating other complications.3 Thus, there is a need for developing a living tissue engineered whole heart for transplantation to provide an alternative option for patients on the waitlist to receive a donor heart.
Our solution is to create acellular myocardial tissue scaffolds seeded with autologous cells corresponding to the patient’s heart. Once the cell seeded scaffold is conditioned and prepared to support life, it would not elicit an immune response post-implantation. The goal of this project is to reconstitute the endocardium in both ventricles of decellularized rabbit myocardium with clinically relevant cell types and hydrogels.
We first developed a bi-ventricle perfusion decellularization procedure which yielded fully acellular hearts. The shape, architecture, and most of the extracellular matrix components of the scaffolds were preserved. Some minor drawbacks included partial removal of the basal lamina components and increased scaffold porosity.
Next, we performed a series of cell seeding and hydrogel infusion experiments to develop a procedure for delivering the necessary components for rebuilding the endocardium. To help us reach our goal, several devices were designed and developed along the way including a 3-D printed stand and funnel for gravitational seeding and a rotational bioreactor system. Our final procedure utilized a layer-by-layer method for administering human endothelial cells, human fibroblast cells, collagen hydrogel, and fibrin hydrogel. Using different analysis techniques, we found hydrogels infused onto the surfaces of the ventricle cavities and cells affectively adhered to the linings of ventricles while remaining active through secreting matrix proteins. However, we could not fully cover the entire surfaces of the ventricles with our tissue engineered endocardium. Future work will be geared towards developing a uniform inner lining of the ventricles.
References for abstract
1. Mozaffarian, D. et al. Executive summary: Heart disease and stroke statistics-2016 update: A Report from the American Heart Association. Circulation 133, 447–454 (2016).
2. Transplant Trends. Available at: https://www.unos.org/data/transplant-trends/. (Accessed: 15th December 2017)
3. Momtahan, N., Sukavaneshvar, S., Roeder, B. L. & Cook, A. D. Strategies and Processes to Decellularize and Recellularize Hearts to Generate Functional Organs and Reduce the Risk of Thrombosis. Tissue Eng. Part B Rev. 21, 115–132 (2015).
Compton, Clayton Lewis, "Regeneration of the Ventricular Endocardium Within Acellular Whole Rabbit Hearts Using a Layer-by-Layer Seeding Method" (2018). All Theses. 3138.