Author + information
- Valentina Lintas1,
- Emanuela Fioretta1,
- Petra Dijkman1,
- Etem Caliskan2,
- Hector Rodriguez3,
- Nikola Cesarovic4,
- Simon Hoerstrup5 and
- Maximilian Emmert6
- 1University of Zurich, Zurich, Switzerland
- 2Clinic for Cardiac Surgery, University Hospital of Zurich, Zurich, Switzerland
- 3University Hospital of Zurich, Zurich, Switzerland
- 4Universitätsspital Zürich, Zürich, Switzerland
- 5University Zuerich, Zuerich, Switzerland
- 6UniversitätsSpital Zürich, Zurich, Switzerland
In the past decade transcatheter valve replacement technologies have remarkably evolved and are in the process to be extended to intermediate and lower risk patients. Nonetheless, all current bioprostheses used for such approaches are predisposed to tissue deterioration and calcification, hence limiting their durability. Transcatheter based tissue engineered heart valves (TEHVs) may overcome these limitations and may thus represent a next generation transcatheter aortic valve replacement (TAVR) concept facilitating lifelong valve substitutes. After the promising outcomes of such TEHVs in the pulmonary position, we here report the proof-of-concept of novel off-the-shelf transcatheter aortic TEHVs using a state-of-the-art, anatomically orienting delivery system.
Off-the-shelf TEHVs derived from human fibroblasts were cultured in a bioreactor, decellularized and sewn onto anatomically orienting TAVR systems (JenaValve, Irvine, US). The valves were implanted transapically into sheep (n=3) and tested for acute functionality including angiography and transesophageal echocardiography. Thereafter they underwent macroscopy and histological assessment. 3D CT reconstruction of the TEHV positioning within the aortic root was performed post-mortem.
Valve delivery and deployment were successful in all animals. Upon implantation, angiography demonstrated correct positioning and good acute functionality. Echocardiographic examination displayed sufficient valve function with proper leaflet mobility, satisfactory coaptation with a mild-to-moderate insufficiency and negligible paravalvular leak. At explantation, the valves showed intact pliable leaflets without thrombi or crimping damages. Histology revealed a dense collagenous matrix with scaffold residuals.
This proof-of-concept study showed good and encouraging initial performance of our novel off-the-shelf TEHVs as aortic valve replacements. Further in-vitro functionality tests and chronic animal studies are underway to validate these findings. Once proven its long-term efficacy, this technology could serve as a basis to provide next generation regenerative aortic valve substitutes for younger patient populations.
OTHER: Pre-Clinical/First In-Human Studies