Pre-clinical results recently published in Science Translational Medicine demonstrate that valve remodeling can be successfully guided towards native-like form and function via computationally optimizing the valve design
A recent collaborative study of the University of Zurich, Eindhoven University of Technology, and the German Heart Center Berlin has demonstrated that the long-term remodeling and functionality of tissue-engineered heart valves can be successfully guided and predicted using computational modeling. The results of this integrated in silico, in vitro, and in vivo study have been published in Science Translational Medicine.
Contemporary heart valve replacements do not consist of living tissue and, therefore, they cannot grow or remodel in response to changes in demands or somatic growth of the patient. Tissue-engineered heart valves (TEHVs) have the potential to overcome these limitations due to their intrinsic growth and remodeling capacity. Still, the observed evolution of TEHVs in pre-clinical studies is often far from optimal due to insufficient understanding of the mechanobiological mechanisms responsible for valve adaptation. One of the major problems in this context is the gradual development of leaflet shortening, which ultimately leads to a loss of valve functionality, usually within a few months after implantation.
In the current study, the authors used computational modeling to propose a valve design to minimize and ideally prevent the development of leaflet shortening via providing a superior, more native-like, mechanical state to the infiltrating cells. This valve design was implemented in the in vitro culture procedure, and subsequently tested via long-term in vivo experiments in a translational sheep model, where almost all the implanted valves demonstrated clinical grade performance during the full one-year follow-up period. Moreover, the observed remodeling response towards native-like configurations of the valves could be accurately predicted using computational remodeling algorithms. Particularly this latter aspect has important value for clinical translation, as it enables the evaluation of the robustness and safety of the technology, and allows for further design optimizations in the future.
The work in this study was performed within the EU-funded LifeValve project (FP7/2007-2013, under grant agreement no. 242008), coordinated by the University of Zurich. The pre-clinical experiments and analysis were performed at the German Heart Center Berlin and the University of Zurich. At the Eindhoven University of Technology, the computational work was performed, and the valves were produced using patented technology.
Read the full article here: https://stm.sciencemag.org/content/10/440/eaan4587