Aortic valve disease represents a major cause of death worldwide. Transcatheter aortic valve implantation (TAVI) has become a valid treatment option and is currently being extended to younger patients. However, available bioprostheses used for TAVI are prone to degeneration, and patients therefore often require multiple re-interventions.The EU-funded TAVI4Life project aims to develop an innovative bioengineered aortic valve prosthesis that combines a regenerative stent and a valve capable of undergoing guided in situ remodelling which is particularly beneficial for young patients. An unconventional bioengineering approach using in vitro, in silico, and in vivo methods will be taken for this novel prosthesis that transforms into a native-like aortic valve and lasts for life.
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, we 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 regenerative stent and applying an unconventional bioengineering approach combining in-vitro, in-silico, and in-vivo TE methods. First, we 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, we will design and develop a novel stent and implement an analytical valve design to develop the transcatheter prosthesis (in-silico). Finally, we 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.
