A lifelong transcatheter aortic valve prosthesis

ongoing

Transcatheter aortic valve implantation (TAVI) techniques have revolutionized the therapy options for valvular heart disease. Initially developed for elderly high-risk patients, TAVI is being extended to younger patients and may become a first-line treatment in the near future. However, the available bioprostheses for TAVI are prone to degeneration, and patients may thus require multiple re-interventions, significantly affecting their life quality. To date, a native-analogous TAVI prosthesis with in-situ remodeling capacity does not exist. Tissue engineered (TE) heart valves represent a potential solution, but are not yet suitable for high-pressure applications and lack clinical translation because of uncontrolled in-vivo remodeling, impairing their long-term functionality. In the TAVI4Life project, I aim to develop and validate a novel TAVI prosthesis for young patients with the unique ability to transform into a fully autologous valve within the body and last for life. This project will go far beyond previous TE concepts by engineering a novel decellularized human ECM and a bioresorbable stent and applying an unconventional bioengineering approach combining in-vitro, in-silico, and in-vivo TE methods. First, I will engineer and characterize a clinical-grade ECM for high-pressure conditions and test patient-specific immuno- and hemocompatibility profile (in-vitro). Next, using computational modeling, I will design and develop a bioresorbable stent and implement an analytical valve design to develop the transcatheter prosthesis (in-silico). Finally, I will evaluate valve performance and remodeling in a preclinical large animal model (in-vivo). This highly multidisciplinary approach will lead to a valve prosthesis that lasts for life, as guided in-situ tissue remodeling will enable their long-term performance. The clinical impact will be enormous as, particularly for young patients, the TAVI4Life will significantly enhance their life expectancy and quality of life.