Experimental investigations and modeling of biohybrid heart valves including tissue maturation – from in vitro to in situ tissue engineering

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The long-term function of biohybrid implants (e.g. heart valves) is significantly related to the production of the extracellular matrix (ECM) with regard to quantity and quality. The ECM has to provide long-term structural support to withstand a large number of mechanical load cycles (90,000 opening and closure procedures of the heart valve per day). Different production approaches (in vitro, in situ and perioperative) to achieve optimal ECM production have been proposed. The integration of a load orientated textile structure into the implant serves, during the production process, as (i) a biomimetic reinforcement and (ii) a guide for the direction of growth of the ECM. The evaluation of the optimal balance between load-bearing reinforcement and remaining biomechanical stimuli on the ECM, to cause desirable orientation into the load direction, is empirically hardly possible. As a result, a demand for suitable models arises to simulate the implant under in vitro and in vivo conditions and to further support the design planning phase. The aim of this project is to enhance the simulation and modelling tool developed in the previous project, to accurately predict the mechanical behavior of biohybrid heart valve implants throughout the in-vitro and in-vivo maturation processes. Furthermore, to model the degradation and damage of the mechanical properties after implantation due to high cycle fatigue. By gradually including the results of the subprojects P1 (hydrogel material), P2 (mechanical properties of scaffold), P6 (degradation behavior of the material) and P7 (textile reinforcement) this model will assist the product design (regarding the technical configuration of the textile reinforcement). It will generate insights into the complex growth and remodeling process and thus support the optimization of the biohybrid implant for all the cultivation methods. The validation of the simulation tool is captured by a trial in a large animal model using all three maturation methods. Validation is especially important to study the long-term damage of the heart valve (TexValve).