Project Details
Projekt
The influence of NO releasing and DNase functional surface on platelet activation and resulting NET formation in oxygenator thrombosis – an in vivo and in vitro evaluation
Subject Area
Medical Physics, Biomedical Technology
Term
since 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 347367912
Extracorporeal lung assist (ECLA) is a life saving measure for patients suffering from acute pulmonary failure. Despite several improvements of recent ECLA devices (e.g. anticoagulant coatings, reduced shear stress, miniaturization), the technology is still prone to diverse complications. Thrombus formation on the membrane is still one of the most critical events. New concepts are needed to reach the next level in ECLA technology, aiming towards long-term hemocompatible and implantable artificial lungs. The process of thrombus formation is influenced from many different factors. Besides the intrinsic- , extrinsic-, and plasmatic-coagulation, the crosstalk between platelets (PLTs) and neutrophil granulocytes plays an essential role. Neutrophil extracellular trap (NET) release is triggered by the contact of neutrophils to activated PLTs. NETs are webs of decondensated nuclear DNA, which promote the connection of fibrin, platelets and other blood cells to a stable clot, and provide an anchoring point for platelets and neutrophils. Thus, NETs critically influence the process of stable thrombus formation on the oxygenator membrane, which is a very frequent event during ECLA therapy. To target oxygenator thrombosis this project aims at the following, new local anticoagulation strategies:1. Polymethylpentene (PMP) oxygenator membranes will be covalently coated with NO releasing (NOrel) microgels to prevent PLT-activation.2. DNase functional microgels will be coated on PMP-membranes to target NET-formation.3. A combination of both coatings will be applied to PMP-membranes to identify possible additive effects.After a stepwise optimization of these three coatings, we will perform extensive testing using in vitro test circuits with human blood and an in vivo ECMO mice model to analyse and compare the effectiveness of the coatings with respect to a reduction of oxygenator thrombosis.
DFG Programme
Priority Programmes
Subproject of
SPP 2014:
Towards an Implantable Lung
Co-Investigators
Professor Dr. Andrij Pich; Professor Dr. Jan Rossaint
