Morgan Caudill
Research Mentor(s): Orsolya Lautner-Csorba
Mentor Department: Medicine
Authors: Morgan Caudill, Tridib Chakraborty, Ryan Kauffman, Joseph Hill, Robert Bartlett, Gergely Lautner, Alvaro Rojas-Peña, Orsolya Lautner-Csorba
Session: Session 4 (1:00pm – 1:50pm)
Presentation Type: Oral
Abstract
Objective: Biomaterials are essential tools in medical applications and gaining more attention – especially those that try to mimic the body’s natural mechanism. One of the biggest challenges in extracorporeal membrane oxygenation (ECMO) – employed in the event of complex cardiac and/or respiratory organ failure – is bleeding and clotting. To mitigate this, our laboratory has developed an antithrombogenic extracorporeal circuit (ECC) by incorporating a novel nitric oxide (NO) donor molecule into a medical grade circuit tubing to eventually avoid the need of systemic anticoagulation. S-nitroso-1-adamantanethiol (SNAT), is the nitrosated derivative of the ‘lipophilic bullet’ 1-adamantanethiol, which is a powerful molecule used in various disease treatments. The novel SNAT-modified medical grade circuit releases NO similar to our body’s endothelium to accomplish the same anticoagulatory effects. Methods: To construct the ECC, a surface modification process called “semi impregnation†was employed, created by infusing the inner lumen of the circuit with the NO donor (SNAT) dissolved in a combination of organic solvents. The NO release profile of the circuit was analyzed by an NO analyzer at initial creation, along with after 1 month of storage (at -20°C (n=3), at room temperature, RT (n=3)). The mechanical strength of the SNAT ECC was measured by a texture analyzer and the data was compared to the untreated ECC (control). Scanning electron microscopy (SEM) was also used to characterize the surface roughness of the SNAT ECC. After thorough in vitro testing, the antithrombogenic capacity of the SNAT ECC was challenged in a short-term rabbit model of arteriovenous shunt. The animal’s hemodynamics were recorded along with important coagulation parameters such as: platelet count, platelet function (aggregometry), thrombin clotting time, fibrinogen, d-dimer, plasma-free hemoglobin (PfHb), and methemoglobin (MetHb) as a marker for NO toxicity. Results: The normal endothelial level of NO is 0.5-4 x 10-10 mol min-1 cm-2 and our SNAT circuit provided that for an impressive 21-day long period in a gradually decreasing fashion. After a month-long storage at RT, the circuit only released adequate NO (>0.5 flux) for a day, however, at -20°C, the storage stability was significantly better (measurement still ongoing) and is in line with typical freshly made circuits. The mechanical testing showed no difference when the Young’s modulus of the SNAT ECC (4.8±0.32 MPa) was compared to the control circuit (4.7±1.09 MPa). The SEM showed no difference in surface characteristics between the control and the SNAT ECC. These data suggested that the SNAT ECC was viable for in vivo testing. After 4h of continuous blood exposure of the circuits, minimal thrombus formation was observed in the SNAT ECC (0.5 ±0.4 cm2), with the platelet counts being preserved, and flow rates being adequate. Further, the MetHb, the PfHb and D-Dimer (hemolysis), as well as the fibrinogen levels remained below clinical relevance. The thrombin clotting time did not change significantly compared to baseline or control. However, the untreated control circuit showed significant clot formation (10.95 ±0.95 cm2), fluctuating flow conditions and decreasing cell counts. Conclusions: The in vitro and in vivo testing have demonstrated the excellent antithrombogenic properties of the novel SNAT-based technology in ECCs. Our future objectives include assessing long-term storage stability (>months) to ensure functionality over time, as well as conducting leaching and cytotoxicity studies to further confirm biocompatibility.
