From the Chair in Engineering Organ Support Technologies, Department of Biomechanical Engineering, Faculty of Engineering Technologies, University of Twente, Enschede, The Netherlands.
Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Medical Faculty.
ASAIO J. 2020 Aug;66(8):847-854. doi: 10.1097/MAT.0000000000001139.
Only a very small portion of end-stage organ failures can be treated by transplantation because of the shortage of donor organs. Although artificial long-term organ support such as ventricular assist devices provide therapeutic options serving as a bridge-to-transplantation or destination therapy for end-stage heart failure, suitable long-term artificial lung systems are still at an early stage of development. Although a short-term use of an extracorporeal lung support is feasible today, the currently available technical solutions do not permit the long-term use of lung replacement systems in terms of an implantable artificial lung. This is currently limited by a variety of factors: biocompatibility problems lead to clot formation within the system, especially in areas with unphysiological flow conditions. In addition, proteins, cells, and fibrin are deposited on the membranes, decreasing gas exchange performance and thus, limiting long-term use. Coordinated basic and translational scientific research to solve these problems is therefore necessary to enable the long-term use and implantation of an artificial lung. Strategies for improving the biocompatibility of foreign surfaces, for new anticoagulation regimes, for optimization of gas and blood flow, and for miniaturization of these systems must be found. These strategies must be validated by in vitro and in vivo tests, which remain to be developed. In addition, the influence of long-term support on the pathophysiology must be considered. These challenges require well-connected interdisciplinary teams from the natural and material sciences, engineering, and medicine, which take the necessary steps toward the development of an artificial implantable lung.
由于供体器官短缺,只有一小部分终末期器官衰竭可以通过移植来治疗。虽然心室辅助装置等人工长期器官支持为终末期心力衰竭提供了治疗选择,作为移植前的桥梁或终末期的治疗方法,但合适的长期人工肺系统仍处于早期开发阶段。尽管目前可以短期使用体外肺支持,但目前可用的技术解决方案不允许在可植入人工肺方面长期使用肺替代系统。这主要受到以下多种因素的限制:生物相容性问题导致系统内形成血栓,尤其是在血流条件不生理的区域。此外,蛋白质、细胞和纤维蛋白沉积在膜上,降低气体交换性能,从而限制了长期使用。因此,需要协调基础和转化科学研究来解决这些问题,以实现人工肺的长期使用和植入。必须找到改善外来表面生物相容性、新抗凝方案、优化气体和血液流动以及这些系统小型化的策略。这些策略必须通过体外和体内测试进行验证,而这些测试仍有待开发。此外,还必须考虑长期支持对病理生理学的影响。这些挑战需要来自自然和材料科学、工程和医学的紧密联系的跨学科团队,朝着开发可植入人工肺的方向迈出必要的步骤。