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治愈。然而，捐献器官的有限供应导致世界各地许多人死亡。尽管体外肺辅助设备（ECLA）可以在有限的时间内接管肺的功能，但像植入式阿尔蒂肺（IAL）这样的持久解决方案仍然遥不可及。目前的ECLA系统都是基于中空纤维（HF）膜的，它们与所需的O2和CO2交换率作斗争，并最终避免了血液凝固。血液凝固是由中空纤维排列所固有的不可避免的死区引起的。因此，没有基于现有系统构建植入式设备的技术路径。过去几年来，增材制造技术的巨大进步使得能够制造更复杂的几何形状。这使我们能够构想出全新的系统，克服当前的技术前沿。数学优化的结构，所谓的三重周期最小表面（TPMS），承诺上级表面体积比，改善被动混合和消除死区。这些TPMS结构是从根本上改善膜性能和有机模拟设计的理想选择。在我们的前一个SPP项目“ECMO应用的3D打印膜架构”中，我们成功制造了TPMS形状的多孔3D膜，并证明了其优于中空纤维膜。在这一重大里程碑的鼓舞下，我们现在提出开发第一个真正的植入式阿尔蒂肺。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：凭借医学专业知识和对IAL手术可能性的估计，将确定艾德关于形状，体积和与患者/空气供应连接的几何约束。我们将推导出的IAL的设计策略，通过模拟和开发的IAL的最佳架构，以最大限度地提高几何约束内的气体交换。由此产生的复杂架构将在增材制造的帮助下制造。将采用先进的膜制造方法来满足本项目的需要。最后，第一个植入式阿尔蒂肺将在本项目的框架内使用新的先进动物模型系统进行体外、离体和体内测试。这个项目的路径走向植入式阿尔蒂肺。

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.