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

生物混合心脏瓣膜的实验研究和建模，包括组织成熟——从体外到原位组织工程

• 批准号: 403471716
• 负责人: Professor Dr. Stefan Jockenhövel
• 金额: --
• 依托单位: Rektor der Universität Siegen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/403471716?language=en
• 关键词: Experimental; investigations; modeling; biohybrid; heart

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).

生物混合植入物（例如心脏瓣膜）的长期功能与细胞外基质（ECM）的产量和质量显著相关。ECM必须提供长期的结构支撑，以承受大量的机械负载循环（每天90，000次心脏瓣膜的打开和关闭手术）。已经提出了不同的生产方法（体外，原位和围手术期），以实现最佳的ECM生产。在生产过程中，将负载定向的纺织结构整合到植入物中用作（i）仿生增强和（ii）ECM生长方向的引导。根据经验，评估ECM上的承重加固和剩余生物力学刺激之间的最佳平衡，以使其在载荷方向上产生理想的定向几乎是不可能的。因此，需要合适的模型来模拟体外和体内条件下的植入物，并进一步支持设计规划阶段。本项目的目的是增强先前项目中开发的模拟和建模工具，以准确预测生物混合心脏瓣膜植入物在体外和体内成熟过程中的机械行为。此外，模拟植入后由于高周疲劳引起的机械性能退化和损坏。通过逐步纳入子项目P1（水凝胶材料）、P2（支架的机械性能）、P6（材料的降解行为）和P7（织物加固）的结果，该模型将有助于产品设计（关于织物加固的技术配置）。它将深入了解复杂的生长和重塑过程，从而支持所有培养方法的生物杂交植入物的优化。通过使用所有三种成熟方法在大型动物模型中进行试验来捕获模拟工具的验证。验证对于研究心脏瓣膜（TexValve）的长期损伤尤为重要。