Toward a Long-Term Artificial Lung

Abstract

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 endstage heart failure, suitable long-term artificial lung systems are still at an early stage of development. Although a shortterm 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. ASAIO Journal XXX; XX:00-00.

Electron Microscopic Confirmation of Anisotropic Pore Characteristics for ECMO Membranes Theoretically Validating the Risk of SARS-CoV-2 Permeation

“…Plasma leakage has always been an issue, and its importance is once again recognized due to the current COVID-19 pandemic. In the future, it is necessary to develop next-generation membranes and systems with long-term durability suitable for treatment [ 31 ] of COVID-19 critically ill patients. Microstructured hollow fiber membranes that increase the gas exchange surface area were also proposed to improve oxygenator performance [ 32 ].…”

Artificial lungs––Where are we going with the lung replacement therapy?

“…An artificial lung should be able to sustain the gas exchange requirements of a normal functioning lung in a way that maintains appropriate blood pressure, decreases injury to blood cells, minimizes clotting, and the immunological response (Table 2). 21 …”

“…Engineering improvements to hollow fiber membrane gas exchangers are enabling longer term wearable systems 20 . Current extracorporeal life support (ECLS) devices are composed of oxygenation membranes produced from polymethylpentene or polypropylene (PP) 21 . Another suitable membrane material for a biohybrid lung assist device is polydimethylsiloxane (PDMS), which is nonporous and provides high gas permeability compared to other polymers 2 .…”

Introducing 3D-potting: a novel production process for artificial membrane lungs with superior blood flow design

“…The exchange is enabled through diffusion of oxygen and carbon dioxide through the HFMs. Despite all the advances in material science, anticoagulation administration, and optimization of the flow design, long-term use of MLs is limited to days or weeks at most due to lack of hemocompatibility [1]. Thrombus formation in combination with protein adsorption is the most frequent clinical complication and can lead to decreased gas transfer performance of the ML, increased embolic risk to the patient, or even mechanical failure of the device that is essential to the patient's survival [2,3].…”

“…Efficient and homogenous perfusion and shear rate distribution within the physiological range is essential to the design and improvement of MLs to avoid thrombosis and blood trauma [1,4,7,21]. The improvement of blood flow inside of MLs is, however, limited to the contour results of the potting process.…”