Teresa Lee
Pronouns: She/Her/Hers
Research Mentor(s): Alvaro Rojas-Peña
Research Mentor School/College/Department: /
Program: RS
Session: Session 1 (9:00am – 9:50am)
Authors: Olivia Lee, Angela Ebreo
Abstract
Patients that require intense cardiovascular care may require extracorporeal membrane oxygenation (ECMO), which allows blood to be “cleaned,†oxygenated, and warmed before circulating back into the patient. Since this procedure can increase the risk of thrombus formation, systemic anticoagulation (e.g., heparin) is routinely used. On the other hand, systemic anticoagulation can cause undesired bleeding or heparin-induced thrombocytopenia (HIT). This study aimed to develop and optimize a more cost-efficient surface anticoagulation method where only the inner surface of the blood-encountering polymer surfaces within the ECMO circuit is modified by a novel technique (semi-impregnation) to release nitric oxide (NO) gas, which has antithrombotic and antibacterial properties. The study also used a new lipophilic, tertiary thiol NO donor (1 g/ml S-nitrosoadamantanethiol, SNAT). Methods: To optimize the NO donor loading and the NO release profile with the least effect on the mechanical properties, different organic swelling solutions of 1:3:1 and a 2:1:2 ratios of acetone, plasticizer, and methanol, respectively were used to semi-impregnate the polymer tubing surface (3/8†ID polyvinyl-chloride, PVC) of the extracorporeal circuit (ECC). During the in vitro tests, first the tensile strength (Young’s modulus) of the ECCs prepared by using 1:3:1 or 2:1:2 solutions was compared using a texture analyzer. The effect of impregnation duration time (4 h, 12 h) on polymer tensile strength was also tested. Samples were analyzed with an ozone chemiluminescent NO analyzer to determine the NO release profile over time. The antibacterial properties (biofilm formation) of the semi-impregnated ECC were assessed in a bioreactor for up to a week for S. aureus and P. aeruginosa bacteria strains. Results: First the tensile strength/Young’s modulus of groups (1:3:1; 2:1:2) with different swelling time (4 h, 12 h) was compared: the group swelled for 4 h was the most similar to that of a naïve control compared impregnation time of 12 h. Thus we prepared the rest of the circuit with a swelling time of 4 h only. Next, the tensile strength of SNAT ECC with 1:3:1 and 2:1:2 solvent ratios was compared to the control. There was no statistical difference (p-value 0.06) between the Young’s Modulus of the 1:3:1 polymer (5.8 MPa, n=3) vs. naïve control (7.2 MPa, n=3). However, the Young’s Modulus of the 2:1:2 polymer (4.1 MPa, n=3) differed significantly from the control (p-value 0.007). The average SNAT loading (data±SEM) of the semi-impregnated ECC was higher with the 2:1:2 ratio (11.7%±0.6, n=8), than with the 1:3:1 (5.5%±0.3, n=9). The 1:3:1 polymer exhibited a NO release of 1.0±0.3 x 10-10 mol min^-1 cm^-2 flux units while the 2:1:2 polymer had a higher NO release of 6.9±2 flux units after 2 weeks. For P. aeruginosa and S.aureus, the 2:1:2 polymer had a ca.3 log reduction in biofilm formation and the 1:3:1 group showed a smaller ca. 1 log reduction for both strains when compared to the control group. Conclusion: This study with the optimization of the NO-releasing chemistry and the impregnation technique proves to be more cost-efficient (50%) compared to full impregnation. We can achieve a high NO loading, a prolonged NO release profile, and a larger log reduction in biofilm formation by using a more apolar swelling solvent despite using less NO donor solution and the impregnation technique proves we can maintain the structural integrity of the circuit. The semi-impregnation with the novel NO donor SNAT can expand on the anticoagulation palette of surface modification in extracorporeal circuit applications.
