3DLung - Implantable Artifical Lung Based on Three-Dimensional Membranes

许多慢性呼吸道疾病只能通过肺移植来治愈。然而，捐赠器官的有限供应导致了世界各地的许多人死亡。尽管体外肺辅助装置(Ecla)可以在有限的时间内接管肺的功能，但像植入性人工肺(Ial)这样的持久解决方案仍然看不到。目前的ECLA系统都是基于中空fiBer(HF)膜，与所需的O2和CO2交换率作斗争，最终阻止flow诱导的血液凝结。血液凝结是由中空fiBER安排所固有的不可避免的死区引起的。因此，在现有系统的基础上建造可植入设备是没有技术途径的。在过去的几年里，添加剂制造技术的巨大进步使得制造更复杂的几何形状成为可能。这使我们能够设想全新的系统，这些系统将克服当前的技术前沿。经过数学优化的结构，即所谓的三周期最小表面(TPMS)，保证了优异的表面积与体积比，改进了被动混合并消除了死区。这些TPMS结构是从根本上改善膜性能和有机仿生设计的理想选择。在我们的前身SPP项目“用于ECMO的3D打印膜结构”中，我们成功地制备了TPMS形状的多孔3D膜，并证明了其相对于中空fi膜的优越性。在这一重大里程碑的鼓舞下，我们现在提议开发fi第一个真正可植入的人工肺。我们的跨学科工作组旨在通过以下工作计划实现这一雄心勃勃的目标：借助IAL的医疗专业知识和对手术可能性的估计，将识别与形状、体积和与患者/空气供应的连接有关的几何约束。我们将通过flow模拟得出IAL的设计策略，并开发IAL的最佳架构，以在几何约束下最大限度地实现气体交换。由此产生的复杂建筑将在加法制造的帮助下制造出来。将采用先进的膜制作方法来满足该项目的需要。最后，将在该项目的框架内使用新的先进的动物模型系统进行体外、体外和体内测试，以测试fi第一个可移植人工肺。这个项目为一种可植入的人工肺开辟了道路。

Many chronic respiratory diseases can only be cured by lung transplants. However, the limited availability of donor organs leads to many deaths worldwide. Although extracorporeal lung assist devices (ECLA) can take over the lung’s function for a limited time, lasting solutions like an implantable artificial lung (IAL) remain out of sight. Current ECLA systems, all based on hollow-fiber (HF) membranes, struggle with the required O2 and CO2 exchange rates and eventually suffer from flow-induced blood clotting. Blood clotting is caused by unavoidable dead zones inherent to hollow-fiber arrangements. Hence, there is no technological path to build implantable devices based on existing systems. The tremendous progress in additive manufacturing technology over the last years enables the fabrication of much more complex geometries. This allows us to conceive totally new systems that will overcome current technical frontiers. Mathematically optimized structures, so-called triply periodic minimal surfaces (TPMS), promise superior surface to volume ratios, improved passive mixing and elimination of dead zones. These TPMS structures are ideal for a fundamentally improved membrane performance and organomimetic design. In our predecessor SPP project ”3D-printed membrane architectures for ECMO application”, we successfully fabricated porous 3D-membranes in the shape of a TPMS and proved their superiority over hollow fiber membranes. Encouraged by this major milestone we now propose to develop the first truly implantable artificial lung.Our interdisciplinary working group aims to achieve this ambitious goal with the following work program: With the medical expertise and estimation of surgical possibilities for the IAL, the geometrical constraints regarding the shape, volume and connectivity to patient/air supply will be identified. We will derive design strategies for the IAL by flow simulations and develop the optimal architecture of the IAL to maximize gas exchange within the geometric constraints. The resulting complex architecture will be fabricated with the help of additive manufacturing. Sophisticated methods for membrane fabrication will be adapted to meet the needs of this project. Finally, the first implantable artificial lung will be tested in the framework of this project in-vitro, ex-vivo and in-vivo tests using new advanced animal model systems. This project paths the way towards an implantable artificial lung.