Multiscale and Multiphysics Optimization of an Implantable Biohybrid Lung

• Applicant: Dr.-Ing. Sotirios Korossis, Ph.D.
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Medical Physics, Biomedical Technology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 348028075

The aim of this project is to develop computational models for optimizing the design and operation, as well as assessing the post-operative performance of a biohybrid intracorporeal membrane oxygenator (iCMO). Specifically, this project will focus on developing a computational modelling platform for interrogating different oxygenator geometries, gas-exchange membrane configurations and integrated blood pump units, in terms of haemodynamics, and its association to thrombogenicity within the oxygenator, oxygenator membrane gas species transport, cannulation technique, and operation mode for different degrees of lung dysfunction. Currently, the only long-term option for patients suffering from end-stage lung disease is lung transplantation. The patients in the lung transplantation list, however, greatly outnumber the available lung transplants, resulting in only a small percentage of patients receiving a lung transplant. Extracorporeal membrane oxygenation (ECMO) is an established therapeutic tool in modern intensive care units, which is primarily employed as a bridge to transplantation. The most frequent complications associated with the use of ECMO are thrombosis, and associated thromboembolism, and inflammatory reaction that arise from the direct blood contact with the artificial ECMO components. These complications limit ECMO usage to between 4-6 weeks and in specialized intensive care units, where it is used almost exclusively in sedated patients receiving invasive mechanical ventilation. The development of an improved oxygenator that can be used for months or even years, significantly improving the prospects and quality of life of patients, represents a step change in assisted oxygenation as a bridge, or as an alternative, to lung transplantation. To achieve this, oxygenators need to become fully haemocompatible and partially, or fully implantable. This entails the overcoming of a number or obstacles, including oxygenator and pump unit miniaturization for easy and safe implantation, vascular access and gas delivery, and gas-exchange membrane haemocompatibility to avoid coagulation and infection, as well as the optimization of parameters such as oxygenator and pump geometry, configuration and in situ positioning, and operating conditions for different degrees of lung dysfunction. Recent advances in computational power and software have made possible the development of sophisticated 3D multiphysics and multiscale models that are able to predict the haemodynamics and gas-species transport and their effect on oxygenator and pump unit function and operation. With a view to an implantable hollow-fiber biohybrid lung that is fully endothelialised to provide the necessary haemocompatibility, the proposed research will generate a fully assessed (in silico and in vitro) implantable oxygenator and integrated pump unit prototype, which will be able to be safely endothelialised prior to implantation.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2014: Towards an Implantable Lung