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Zwitterionic Poly-Carboxybetaine Coating Reduces Artificial Lung Thrombosis in Sheep and Rabbits

32 Pages Posted: 24 Jan 2019 First Look: Accepted

See all articles by Rei Ukita

Rei Ukita

Carnegie Mellon University - Department of Biomedical Engineering

Kan Wu

University of Washington - Department of Chemical Engineering

Xiaojie Lin

University of Washington - Department of Chemical Engineering

Neil M. Carleton

Carnegie Mellon University - Department of Biomedical Engineering

Noritsugu Naito

Carnegie Mellon University - Department of Biomedical Engineering

Angela Lai

Carnegie Mellon University - Department of Biomedical Engineering

Chi Chi Do-Nguyen

Carnegie Mellon University - Department of Biomedical Engineering

Caitlin T. Demarest

Carnegie Mellon University - Department of Biomedical Engineering

Shaoyi Jiang

University of Washington - Department of Chemical Engineering

Keith Cook

Carnegie Mellon University - Department of Biomedical Engineering

Abstract

Current artificial lungs fail in 1-4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N=5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220-300s (N≥5). Here, DOPA-pCB reduced fibrin formation (p=0.06) and gross thrombus formation by 59% (p < 0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs.

Keywords: artificial lung, thrombosis, zwitterion, carboxybetaine, 3,4-dihydroxyphenylalanine (DOPA)

Suggested Citation

Ukita, Rei and Wu, Kan and Lin, Xiaojie and Carleton, Neil M. and Naito, Noritsugu and Lai, Angela and Do-Nguyen, Chi Chi and Demarest, Caitlin T. and Jiang, Shaoyi and Cook, Keith, Zwitterionic Poly-Carboxybetaine Coating Reduces Artificial Lung Thrombosis in Sheep and Rabbits (January 22, 2019). Available at SSRN: https://ssrn.com/abstract=3320741

Rei Ukita (Contact Author)

Carnegie Mellon University - Department of Biomedical Engineering ( email )

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

Kan Wu

University of Washington - Department of Chemical Engineering

Seattle, WA 98195
United States

Xiaojie Lin

University of Washington - Department of Chemical Engineering

Seattle, WA 98195
United States

Neil M. Carleton

Carnegie Mellon University - Department of Biomedical Engineering

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

Noritsugu Naito

Carnegie Mellon University - Department of Biomedical Engineering

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

Angela Lai

Carnegie Mellon University - Department of Biomedical Engineering

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

Chi Chi Do-Nguyen

Carnegie Mellon University - Department of Biomedical Engineering

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

Caitlin T. Demarest

Carnegie Mellon University - Department of Biomedical Engineering

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

Shaoyi Jiang

University of Washington - Department of Chemical Engineering

Seattle, WA 98195
United States

Keith Cook

Carnegie Mellon University - Department of Biomedical Engineering ( email )

5000 Forbes Avenue
Scott Hall 4N201
Pittsburgh, PA 15213-3891
United States

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