The effect of a polyurethane coating incorporating both a thrombin inhibitor and nitric oxide on hemocompatibility in extracorporeal circulation

Major, Terry C.; Brisbois, Elizabeth J.; Jones, Anna M.; Zanetti, Margaux E.; Annich, Gail M.; Bartlett, Robert H.; Handa, Hitesh

doi:10.1016/j.biomaterials.2014.05.036

Cited by 77 publications

(98 citation statements)

References 50 publications

(51 reference statements)

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“…Even though the argatroban circuits showed significant reduction in thrombus formation compared to the controls (Figure 7b), argatroban, a direct thrombin inhibitor, is only an anticoagulant; similar to heparin, it has no effect on preventing platelet activation. The platelet count data here confirms this and points to previous work that showed both an anticoagulant and antiplatelet agent, such as nitric oxide, are necessary to completely prevent ECC clotting 27 .…”

Section: Resultssupporting

confidence: 91%

“…Modifications were made to the technique established by Major et al 8 . Previous work utilized a 2 h incubation period for HMDI incorporation into CarboSil ® and overnight incubation for argatroban attachment to CarboSil®/HMDI.…”

Section: Resultsmentioning

confidence: 99%

“…In order to prevent thrombosis within the extracorporeal circuit, antithrombotic therapy is required. The potential for argatroban as a polymer surface coating was first evaluated by Major et al 8 . Results from that study showed that argatroban maintains its antithrombin activity when immobilized within a polymer coating, allowing its consideration as a nonthrombogenic coating material for ECLS devices.…”

Section: Discussionmentioning

confidence: 99%

“…Systemic anticoagulation, however, places patients at high risk for bleeding, which often can be life-threatening. Although extensive work has been done to develop extracorporeal circuits with nonthrombogenic surface properties, clinical success has been equivocal and the use of such devices has been limited to specific clinical scenarios 1–8 . The ideal biomaterial for extracorporeal circulatory devices is one that is similar to vascular endothelium.…”

Section: Introductionmentioning

confidence: 99%

“…Previous work by Major et al 8 demonstrated the potential for a combined direct thrombin inhibitor and nitric oxide releasing polymer as a nonthrombogenic surface coating for extracorporeal devices. This previous work demonstrated both antithrombin and antiplatelet effects in an ECLS circuit after 4 h blood exposure.…”

Section: Introductionmentioning

confidence: 99%

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The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation

Brisbois

Handa

et al. 2016

J. Mater. Chem. B

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A biomaterial with both antithrombin and antiplatelet properties is the ideal surface for use in extracorporeal circulation (ECC) as it targets both fibrin generation and platelet adhesion. A hemocompatible surface coating avoids the need for systemic anticoagulation by providing a local anticoagulant effect at the polymer-blood interface. Previous work has demonstrated the potential use of argatroban, a direct thrombin inhibitor, as a nonthrombogenic material for extracorporeal devices. The work reported here focuses on the characterization of argatroban linked to a polyurethane-silicone polymer, CarboSil®. Chemical immobilization, the amount of argatroban, incubation times, and saturation point were evaluated to achieve maximal antithrombin activity at the polymer surface. Cross-linked polymer coatings reacted with 10 and 30 µmole of argatroban were prepared and tested. These coatings resulted in argatroban activity levels of 0.131 µM and 0.446 µM, respectively. After refining the cross-linking process, argatroban activity increased by approximately 3.6 fold. Maintenance of activity and leaching from the polymer surface were also evaluated. Using the refined process for linking argatroban to polymer, the resulting polymer was applied as a surface coating to the inner lumen of poly(vinyl chloride) ECC circuit tubing and its antithrombin effect evaluated using a 4 h rabbit ECC model. Following 4 h of blood exposure, the argatroban circuit demonstrated significantly less thrombus formation compared to the control CarboSil® coating with a 4.1 cm2 thrombus average area for the control coating compared to 1.2 cm2 for the argatroban coating (n=4). There was no significant change in thrombin time from baseline in plasma from animals in which the argatroban coated circuit was used, with a thrombin time of 16.2 s at t=0 and 14.5 s after 4 h. These results demonstrate the potential efficacy of immobilized argatroban as a hemocompatible biomaterial for extracorporeal life support devices.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation

Brisbois

Handa

et al. 2016

J. Mater. Chem. B

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Introduction of Nature's Complexity in Engineered Blood‐compatible Biomaterials

Ippel

Dankers

2017

Adv Healthcare Materials

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Biomaterials with excellent blood-compatibility are needed for applications in vascular replacement therapies, such as vascular grafts, heart valves and stents, and in extracorporeal devices such as hemodialysis machines and blood-storage bags. The modification of materials that are being used for blood-contacting devices has advanced from passive surface modifications to the design of more complex, smart biomaterials that respond to relevant stimuli from blood to counteract coagulation. Logically, the main source of inspiration for the design of new biomaterials has been the endogenous endothelium. Endothelial regulation of hemostasis is complex and involves a delicate interplay of structural components and feedback mechanisms. Thus, challenges to develop new strategies for blood-compatible biomaterials now lie in incorporating true feedback controlled mechanisms that can regulate blood compatibility in a dynamic way. Here, supramolecular material systems are highlighted as they provide a promising platform to introduce dynamic reciprocity, due to their inherent dynamic nature.

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Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

Zhao

Feng

2020

Adv Healthcare Materials

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Cardiovascular devices have been widely applied in the clinical treatment of cardiovascular diseases. However, poor hemocompatibility and slow endothelialization on their surface still exist. Numerous surface engineering strategies have mainly sought to modify the device surface through physical, chemical, and biological approaches to improve surface hemocompatibility and endothelialization. The alteration of physical characteristics and pattern topographies brings some hopeful outcomes and plays a notable role in this respect. The chemical and biological approaches can provide potential signs of success in the endothelialization of vascular device surfaces. They usually involve therapeutic drugs, specific peptides, adhesive proteins, antibodies, growth factors and nitric oxide (NO) donors. The gene engineering can enhance the proliferation, growth, and migration of vascular cells, thus boosting the endothelialization. In this review, the surface engineering strategies are highlighted and summarized to improve hemocompatibility and rapid endothelialization on the cardiovascular devices. The potential outlook is also briefly discussed to help guide endothelialization strategies and inspire further innovations. It is hoped that this review can assist with the surface engineering of cardiovascular devices and promote future advancements in this emerging research field.

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The effect of a polyurethane coating incorporating both a thrombin inhibitor and nitric oxide on hemocompatibility in extracorporeal circulation

Cited by 77 publications

References 50 publications

The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation

The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation

Introduction of Nature's Complexity in Engineered Blood‐compatible Biomaterials

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

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