TexValveMonitoring - Multimodal longitudinal imaging of biohybrid heart valves

与传统的合成解决方案相比，组织工程心血管植入物有许多优点。例如，它们可以适应个人条件，在儿科应用的情况下，甚至可以与孩子一起成长。然而，这种高适应性带来了重构错误和功能丧失的风险。因此，捕捉重塑过程基本特征的诊断程序对临床翻译至关重要。在PAK961的第一个学期，我们能够开发一种成像概念，使我们能够全面表征组织工程血管移植物（tevg）。本研究采用19F MRI对纺织支架的不可降解组分进行可视化，并用1H MRI对可降解组分进行氧化铁纳米颗粒（SPION）标记后的降解进行评估和量化。此外，我们能够使用分子MRI探针检测新的细胞外基质的合成，分子超声成像为我们提供了内皮细胞激活状态的重要信息。在该项目的第二阶段，我们计划将成像概念转移到组织工程心脏瓣膜。为此，必要的适应性是必要的：一方面，纺织支架的稳定性需要适应更高的机械应力。为此，将对新型“弹性蛋白样重组体”（ELR）进行测试。此外，我们需要对细胞合成细胞外基质有更深入的了解。这里，有趣的是，在体外条件下，我们只观察到胶原蛋白的沉积，而没有观察到弹性蛋白的沉积。内皮细胞和肌成纤维细胞之间αvβ3整合素介导的相互作用不足可能是一个原因。为了通过成像来观察这些过程，必须构建一个与MRI兼容的生物反应器，允许在MRI内控制组织工程心脏瓣膜的跳动，并在不污染或破坏瓣膜的情况下提供超声研究的通道。此外，成像技术必须适应心脏瓣膜的运动。这对于MRI来说尤其具有挑战性，因为小叶很薄，并且可能出现与血流相关的伪影。为了满足这些需求，MR指纹识别技术将与运动门控一起使用。此外，将研究MRI和磁颗粒成像（MPI）相结合是否为快速灵敏检测spion标记纤维的合理选择。因此，我们将为整个联盟开发并提供重要的监测方法，这些方法可用于在生物反应器成熟期间和体内植入后表征组织工程心脏瓣膜。

Tissue-engineered cardiovascular implants have many advantages over conventionally used synthetic solutions. For example, they can adapt to individual conditions and, in the case of pediatric applications, even grow with the child. However, the high adaptability carries the risk of faulty remodeling and thus loss of function. Diagnostic procedures that capture essential features of the remodeling process are, therefore, essential for the clinical translation. In the first term of PAK961, we were able to develop an imaging concept that allows us to comprehensively characterize tissue-engineered vascular grafts (TEVGs). Here, non-degradable components of the textile scaffold could be visualized by 19F MRI, and the degradation of degradable components after labeling with iron oxide nanoparticles (SPION) could be assessed and quantified by 1H MRI. Furthermore, we were able to detect the synthesis of new extracellular matrix using molecular MRI probes, and molecular ultrasound imaging provided us with important information about the endothelial activation state.In the second phase of the project, we plan to transfer the imaging concept to tissue-engineered heart valves. For this, essential adaptations are necessary: On one hand, the stability of the textile scaffold needs to be adapted to the higher mechanical stress. For this purpose, the novel "elastin-like recombinamers" (ELR) will be tested. Furthermore, we need to gain a deeper understanding of the synthesis of extracellular matrix by the cells. Here, it is interesting to note that under in vitro conditions, we only observed deposition of collagen, but not elastin. Insufficient αvβ3 integrin-mediated interactions between endothelial cells and myofibroblasts could be a cause here. To observe these processes by imaging, a bioreactor must be constructed that is MRI compatible, allows the controlled beating of tissue-engineered heart valves inside the MRI, and provides access for ultrasound studies without contaminating or destroying the valves. Furthermore, imaging techniques must be adapted to the moving heart valves. This is particularly challenging for MRI because the leaflets are thin, and flow-related artifacts are expected. To address these demands, the MR fingerprinting technique will be used together with motion gating. Furthermore, the combination of MRI and Magnetic Particle Imaging (MPI) will be investigated whether it is a reasonable option for the fast and sensitive detection of SPION-labeled fibers.Thus, we will develop and provide important monitoring methods for the entire consortium that can be applied to characterize tissue-engineered heart valves during bioreactor maturation and after in vivo implantation.