Novel thromboresistant materials

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Novel thromboresistant materials Sumanas W. Jordan, Elliot L. Chaikof, MD, PhD Journal of Vascular Surgery Volume 45, Issue 6, Pages A104-A115 (June 2007) DOI: 10.1016/j.jvs.2007.02.048 Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

Fig 1 Top, Scheme illustrates in situ polymerization of a phospholipid surface assembly to form a “membrane-mimetic” thin film. A and B, Scanning electron micrographs of a membrane-mimetic thin film that was coated on the inner lumen of an ePTFE vascular graft. Scale bar in A is 385 μm and in B 38.5 μm. FITC, Fluorescein isothiocyanate. (Adapted from Jordan SW, Faucher KM, Caves JM, Apkarian RP, Rele SS, Sun XL, et al. Fabrication of a phospholipid membrane-mimetic film on the luminal surface of an ePTFE vascular graft. Biomaterials 2006;27:3473-81). Journal of Vascular Surgery 2007 45, A104-A115DOI: (10.1016/j.jvs.2007.02.048) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

Fig 2 A, Scheme illustrates an ex vivo femoral arteriovenous shunt to assess platelet deposition in a baboon animal model. B, Platelet deposition normalized by surface area over a 1-hour time period (n = 6). ePTFE, Expanded polytetrafluoroethylene. C, Macroscopic photographs of unstained (left) and Coomassie-stained (right) graft samples after coating with a recombinant elastin protein polymer film. (Adapted from Jordan SW, Haller CA, Sallach RE, Apkarian RP, Hanson SR, Chaikof EL. The effect of a recombinant elastin-mimetic coating of an ePTFE prosthesis on acute thrombogenicity in a baboon arteriovenous shunt. Biomaterials 2007;28:1191-7). Journal of Vascular Surgery 2007 45, A104-A115DOI: (10.1016/j.jvs.2007.02.048) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

Fig 3 A, Rate of thrombin generation as a function of perfusion time at a wall shear rate of 50/s on heparin-bound (▴) or non-heparin containing (■) surfaces in the presence of antithrombin III (ATIII). Thrombin production was initiated by tissue factor deposited in a spatially confined upstream zone. The rate of thrombin production in the absence of surface-bound heparin or antithrombin III is illustrated (•). Each data point represents a mean value with a standard error <10% (n = 5). When compared with the effect of circulating antithrombin III alone, the additional effect of surface bound heparin in inactivating thrombin is small. B, The contact pathway of the coagulation cascade is initiated by activation of factor XII by plasma proteins adsorbed onto a biomaterial surface, as well as by surface bound heparin. However, antithrombin III bound to heparin-coated surfaces inactivates IXa, Xa, and thrombin. Nonetheless, surface bound heparin is ineffective in the inactivation of proinflammatory and procoagulant precursors of thrombin, such as Va and VIIIa. Moreover, heparin coated surfaces do not provide an efficient scheme for inactivating fluid phase thrombin produced by the extrinsic coagulation pathway initiated by the presence of tissue factor present at anastomotic sites, inflammatory cells, or as a circulating soluble factor. (Adapted from Tseng PY, Rele SS, Sun XL, Chaikof EL. Membrane-mimetic films containing thrombomodulin and heparin inhibit tissue factor-induced thrombin generation in a flow model. Biomaterials 2006;27:2637-2650). Journal of Vascular Surgery 2007 45, A104-A115DOI: (10.1016/j.jvs.2007.02.048) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

Fig 4 A, Scheme for site-specific linkage of a recombinant thrombomodulin (rTM) to a surface via “click” alkyne-azide cycloaddition. PBS, Phosphate buffered saline; PEG, polyethylene glycol. B, Thrombomodulin-containing surfaces that produced activated protein C (APC) may be more effective in inactivating proinflammatory and procoagulant precursors of thrombin. Moreover, since APC is released from the surface as a local fluid phase anticoagulant, it may provide a more efficient scheme for inactivating thrombin produced by tissue factor present. (Adapted from Sun XL, Stabler CL, Cazalis CS, Chaikof EL. Carbohydrate and protein immobilization onto solid surfaces by sequential Diels-Alder and azide-alkyne cycloadditions. Bioconjugate Chem 2006;17:52-57). Journal of Vascular Surgery 2007 45, A104-A115DOI: (10.1016/j.jvs.2007.02.048) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

Fig 5 Schematic representation of catalytic nitric oxide (NO) generation at the interface of a polymeric film doped with lipophilic Cu2+ complex when bathed in a solution containing nitrite and ascorbate, a reducing equivalent (Red). Ox, Oxidation product. (Adapted from Oh BK, Meyerhoff ME. Catalytic generation of nitric oxide from nitrite at the interface of polymeric films doped with lipophilic Cu(Il)-complex: a potential route to the preparation of thromboresistant coatings. Biomaterials 2004;25:283-293). Journal of Vascular Surgery 2007 45, A104-A115DOI: (10.1016/j.jvs.2007.02.048) Copyright © 2007 The Society for Vascular Surgery Terms and Conditions