Platform Technologies to Advance Clinically Relevant Tissue Engineered Heart Valve Products
Year: 2014
Type: dissertation
Abstract: Diseased heart valves are commonly replaced by mechanical, bioprosthetic, or allograft heart valves. These replacements provide major improvements in cardiac function and quality of life, but have significant limitations and eventually require surgical replacement within 15-20 years. These risks are particularly prominent in pediatric patients and young adults. The field of tissue engineering and regenerative medicine, which combines scaffolds and cells, holds great promise in developing living replacement heart valves that would self-repair and grow in size along with the growing children.\nThe long-term goal of this project is to generate living, tissue-engineered heart valves from biological scaffolds and autologous stem cells – a goal that hinges on our ability to create tissue devices that withstand mechanical stresses immediately upon implantation without posing risks of immunological rejection. We hypothesized that these valves can be generated by optimal integration of three main factors: acellular heart valve root scaffolds, autologous stem cells, and construct preconditioning in a bioreactor. Furthermore, we hypothesized that the valves would not be generated without advanced bioreactor systems for the development, conditioning, and translation to clinical practice.\nTo reach this goal, we developed integrated platform technologies for complete aortic valve root (AVR) decellularization, stem cell seeding, and dynamic conditioning before implantation. Unique features include universal “no touch” valve-mounting devices, decellularization in a purpose-designed pulsatile perfusion system, and techniques for in vitro re-vitalization with adipose tissue-derived stem cells (hADSCs) followed by progressive conditioning in our heart valve bioreactors. Acellular porcine AVRs seeded with autologous (sheep) ADSCs were implanted in 10 sheep as right ventricle to pulmonary artery shunts with complete clamping of the pulmonary aorta.\nResults showed perfect decellularization of the entire porcine AVR and almost complete seeding with ADSCs. Bioreactor studies revealed stem cell pre-differentiation into cells resembling valvular interstitial cells as a response to dynamic stimulation. Animal studies with follow-ups to 12 months are ongoing.\nNovel customized devices and bioreactor systems are vital to the successful development of tissue engineered heart valve products, especially in preparation for clinical translation. Herein is described some of the basic equipment and expertise necessary for the successful development of tissue-engineered cardiovascular products.
Source: TigerPrints (Clemson University)
Author: Leslie Neil Sierad
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2890346309