Twelve Hours In Vitro Biocompatibility Testing of Membrane Oxygenators

Berne, Christian; Grottke, Oliver; Tillmann, Sabine; Honickel, Markus; Kopp, Rüdger; Rossaint, Rolf

doi:10.1097/mat.0000000000000252

Cited by 13 publications

(14 citation statements)

References 27 publications

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“…Haemolysis indicated by the increase of fHGB after 240 minutes of circulation, is within the same range as previously performed in vitro tests using these test circuits, 14,16 and is not uncommon in clinical ECMO administration. 20 PLT activation after 5 minutes of circulation is similar in both groups, which demonstrates that the prior centrifugation has no measurable impact on the activation of the remaining PLTs in the PLTgroup.…”

Section: Discussionsupporting

confidence: 78%

Platelet count reduction during in vitro membrane oxygenation affects platelet activation, neutrophil extracellular trap formation and clot stability, but does not prevent clotting

et al. 2021

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Introduction: Due to improved technology and increased application the mortality during extracorporeal membrane oxygenation (ECMO) is constantly declining. Nevertheless, complications including haemorrhage or thrombus formation remain frequent. Local mitigation of coagulation within an ECMO system to prevent thrombus formation on ECMO components and optimizing systemic anticoagulation is an approach to reduce clotting and bleeding complications at once. Foreign surfaces of ECMO systems, activate platelets (PLTs), which besides their major role in coagulation, can trigger the formation of neutrophil extracellular traps (NETs) contributing to robust thrombus formation. The impact of a reduced PLT count on PLT activation and NET formation is of paramount importance and worth investigating. Methods: In this study platelet poor (PLT–) and native (PLT+) heparinized human blood was circulated in two identical in vitro test circuits for ECMO devices for 6 hours. PLT reduction was achieved by a centrifugation protocol prior to the experiments. To achieve native coagulation characteristics within the test circuits, the initial heparin dose was antagonized by continuous protamine administration. Results: The PLT– group showed significantly lower platelet activation, basal NET formation and limited clot stability measured via thromboelastometry. Fluorescent and scanning electron microscope imaging showed differences in clot composition. Both groups showed equal clot formation within the circuit. Conclusions: This study demonstrated that the reduction of PLTs within an ECMO system is associated with limited PLT activation and NET formation, which reduces clot stability but is not sufficient to inhibit clot formation per se.

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Section: Discussionsupporting

confidence: 78%

Platelet count reduction during in vitro membrane oxygenation affects platelet activation, neutrophil extracellular trap formation and clot stability, but does not prevent clotting

et al. 2021

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“…It is a fact that many devices are made of materials that have a long history of innocuous use. Therefore, it may not be necessary to test for all endpoints delineated in ISO 10993 on these types of harmless materials, but only if the manufacturing process does not raise any new biocompatibility concerns [ 158 ]. Nevertheless, if the device materials, manufacturing processes, and intended use are not identical to a previously legally marketed device in the United States, then the FDA requires additional biocompatibility testing to be performed.…”

Section: Using the Results From A Previous Biocompatibility Testmentioning

confidence: 99%

The new U.S. FDA regulations on biocompatibility and reprocessing for medical devices

Reifschneider

2018

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The U.S. Food and Drug Administration ("FDA") regulates all medical devices in the United States. As part of its regulatory duties, the FDA provides guidance documents on various regulatory topics as mandated by the U.S. code of federal regulations. Since 2015, the FDA has begun to issue many substantial revisions to their guidance documents that directly affects the regulatory framework on biocompatibility, reprocessing, and sterilization.These regulatory issues are of paramount importance for many companies because of the potential high costs involved in changing their internal design, controls, manufacturing, and quality systems. This master’s thesis examines the various changes made by the FDA in recent years on the inter-related topics of biocompatibility, reprocessing, and sterilization. Some of the major changes by the FDA involve an increase in the importance of chemical characterization, a reduction in the use of animal testing, a requirement for an independent validation of the user instructions for reusable devices, and increased usability testing.The principal reasons for these major policy changes by the FDA are shown to be the major device scandals that recently involved duodenoscopes, metal-on-metal hip implants, and vaginal surgical mesh implants. Along with several other regulatory failures that made national news headlines in the United States, the FDA began to revise several of their previous medical device guidances. The information from this master’s thesis can be used by medical device developers and manufacturers, especially when they are located outside of the United States and lack sufficient regulatory affairs resources to provide independent advice and recommendations on these important FDA changes. A thorough analysis is made of the new FDA guidances to clarify several potentially difficult questions for medical device manufacturers, specifically the following: (1) "Use of International Standard ISO 10993-1, ‘Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process", (2) "Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling", and (3) "Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile". This master’s thesis is intended to provide not only an overview of the current FDA requirements, but to function as a guide for both researchers and engineers to improve their medical device design and development process.

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“…Not only the gas transfer rates over 12 hours but also coagulation activation, as well as some hemocompatibility parameters could be analyzed. 77 However, mainly because of blood deterioration it has not yet been possible to simulate long-term functionality in vitro for a relevant time frame as compared with therapy durations. In addition, to date, these tests are carried out with blood from healthy animals without the respective disease.…”

Section: Development Of Verification and Validation Methods For Lung mentioning

confidence: 99%

Toward a Long-Term Artificial Lung

et al. 2020

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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.

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Twelve Hours In Vitro Biocompatibility Testing of Membrane Oxygenators

Cited by 13 publications

References 27 publications

Platelet count reduction during in vitro membrane oxygenation affects platelet activation, neutrophil extracellular trap formation and clot stability, but does not prevent clotting

Platelet count reduction during in vitro membrane oxygenation affects platelet activation, neutrophil extracellular trap formation and clot stability, but does not prevent clotting

The new U.S. FDA regulations on biocompatibility and reprocessing for medical devices

Toward a Long-Term Artificial Lung

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