In situ tissue engineering of heart valves: Balancing in the dark

At the end stage of heart valve disease, surgical replacement of the diseased valve often is required either via surgical or transcatheter routes. Currently available heart valve prostheses have resulted in an enhanced quality of life and survival rates however at the price of significant drawbacks. The protheses are non-living structures that lack the ability to grow and remodel. In situ tissue engineering (TE) is a technique that aims to overcome these drawbacks. The technique builds up on the regenerative potential of the recipient’s body to remodel an off-the shelf implant i.e., scaffold that is designed to favor host cell adhesion and tissue formation and provide valve functionality immediately upon implantation. To manufacture TE heart valves (HVs), various scaffolds have been explored. In this thesis we focus on bioresorbable synthetic scaffolds. For successful in situ TE of HVs, the synthetic scaffold should support tissue formation while controlled degradation occurs until native-like functional tissue is achieved. This touches upon a crucial challenge of in situ TE of HVs: getting the correct balance between appropriate tissue formation and scaffold degradation.
In this thesis we investigate the feasibility of synthetic scaffolds for in situ TE of HVs with a focus on translational research using animal models. In the first part we explore the current state-of-the-art of valve implantations in large animals and the quality of reporting. In the second part, executed in animal studies, we evaluate how the design of the synthetic scaffold influence the in situ TE processes in vivo.