Investigation of recombinant human elastin polypeptides as non-thrombogenic coatings.

We investigated the use of a recombinant human elastin polypeptide as a coating on synthetic materials with a view to determining if these polypeptides could improve the blood compatibility of cardiovascular devices such as vascular conduits and arterial/venous catheters. Platelet adhesion and activation were studied in vitro using three commercially available synthetic materials: polyethylene terephthalate (Mylar), a poly(tetrafluoroethylene/ethylene) copolymer (Tefzel) and a polycarbonate polyurethane (Corethane). Coated with adsorbed polypeptide, all three synthetic materials demonstrated reduced platelet activation and adhesion in platelet rich plasma in vitro. Compared to non-coated controls, there was a significant decrease (p=0.05) in both platelet microparticle release and P-selectin expression for the polypeptide-coated surfaces. Scanning electron microscopy indicated fewer adhering platelets on coated surfaces compared to non-coated controls. In vivo, in a rabbit model, evaluations of polyurethane catheters coated with the polypeptide showed a marked increase in catheter patency and a significant decrease in fibrin accretion and embolism when compared to uncoated controls. This polypeptide shows a strong potential for use as a non-thrombogenic coating for small diameter vascular grafts. In addition, the results of this study indicate that the elastin polypeptide would be a valuable component of a tissue engineered vascular conduit.

[1]  C. Bellingham,et al.  Elastin as a self-organizing biomaterial: use of recombinantly expressed human elastin polypeptides as a model for investigations of structure and self-assembly of elastin. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[2]  Joseph D. Andrade,et al.  Protein adsorption and materials biocompatibility: A tutorial review and suggested hypotheses , 1986 .

[3]  A. Verna,et al.  Elastin-derived protein coating onto poly(ethylene terephthalate). Technical, microstructural and biological studies. , 2000, Biomaterials.

[4]  P. Robson,et al.  Self-aggregation characteristics of recombinantly expressed human elastin polypeptides. , 2001, Biochimica et biophysica acta.

[5]  G. Goissis,et al.  Preparation and characterization of collagen-elastin matrices from blood vessels intended as small diameter vascular grafts. , 2000, Artificial organs.

[6]  D. Monroe,et al.  Coagulation Factor IXa Binding to Activated Platelets and Platelet-Derived Microparticles: A Flow Cytometric Study , 1992, Thrombosis and Haemostasis.

[7]  Y. Bae,et al.  Heparin release from polymer complex , 1994 .

[8]  K. Woodhouse,et al.  Adsorption of plasminogen from plasma to lysine-derivatized polyurethane surfaces. , 1992, Biomaterials.

[9]  T. Okano,et al.  Blood compatibility of SPUU-PEO-heparin graft copolymers. , 1992, Journal of biomedical materials research.

[10]  G. Whitesides,et al.  Self-assembled organic monolayers: model systems for studying adsorption of proteins at surfaces , 1991, Science.

[11]  A. Weiss,et al.  Biochemistry of tropoelastin. , 1998, European journal of biochemistry.

[12]  R. Gordon,et al.  Co-localization of von Willebrand factor and type VI collagen in human vascular subendothelium. , 1993, The American journal of pathology.

[13]  M. Phaneuf,et al.  In vivo assessment of a novel dacron surface with covalently bound recombinant hirudin. , 1999, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[14]  D. Urry.  On the molecular mechanisms of elastin coacervation and coacervate calcification. , 1976, Faraday discussions of the Chemical Society.

[15]  G. Edwards,et al.  Effects of mesh modification on the structure of a mandrel-grown biosynthetic vascular prosthesis. , 1999, Journal of biomedical materials research.

[16]  K. Woodhouse,et al.  Protein and platelet interactions with thermally denatured fibrinogen and cross-linked fibrin coated surfaces. , 1998, Biomaterials.

[17]  S. Greenwald,et al.  Improving vascular grafts: the importance of mechanical and haemodynamic properties , 2000, The Journal of pathology.

[18]  D. Macintyre,et al.  Platelet-reactivity of isolated constituents of the blood vessel wall. , 1979, Haemostasis.

[19]  M. Phaneuf,et al.  Evaluation of a novel hirudin-coated polyester graft to physiologic flow conditions: hirudin bioavailability and thrombin uptake. , 1998, Journal of vascular surgery.

[20]  J. Polasek.  The appearance of multivesicular structures during platelet activation as observed by scanning electron microscopy. , 1982, Thrombosis Research.

[21]  S. Williams,et al.  Cellular proliferation and macrophage populations associated with implanted expanded polytetrafluoroethylene and polyethyleneterephthalate. , 2000, Journal of biomedical materials research.

[22]  Chiu Yl,et al.  Platelet deposition onto fibrin-coated surfaces under flow conditions. , 1988 .

[23]  C. Esmon,et al.  Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. , 1989, The Journal of biological chemistry.

[24]  M. Sefton,et al.  Platelet-derived microparticle formation involves glycoprotein IIb-IIIa. Inhibition by RGDS and a Glanzmann's thrombasthenia defect. , 1993, The Journal of biological chemistry.

[25]  D. Charlesworth,et al.  Albumin-coated vascular prostheses: A five-year follow-up. , 1996, Journal of vascular surgery.

[26]  R. Glanville,et al.  Morphological relationships of von Willebrand factor, type VI collagen, and fibrillin in human vascular subendothelium. , 1996, The American journal of pathology.

[27]  M. Hara,et al.  Dilatation of sealed Dacron vascular prostheses: a comparison of Gelseal and Hemashield. , 1998, The Journal of cardiovascular surgery.

[28]  P. Trackman,et al.  Oxidation, cross-linking, and insolubilization of recombinant tropoelastin by purified lysyl oxidase. , 1993, The Journal of biological chemistry.

[29]  Ying Jun Du,et al.  Blood-compatible biomaterials by surface coating with a novel antithrombin-heparin covalent complex. , 2002, Biomaterials.

[30]  H. Baumgartner,et al.  Platelet Adhesion, Release and Aggregation in Flowing Blood: Effects of Surface Properties and Platelet Function. , 1976, Thrombosis and Haemostasis.

[31]  M. Packham.  Role of platelets in thrombosis and hemostasis. , 1994, Canadian journal of physiology and pharmacology.

[32]  J. Brash,et al.  Protein adsorption studies on 'standard' polymeric materials. , 1993, Journal of biomaterials science. Polymer edition.

[33]  B. Warren,et al.  The adhesive dendritic pseudopodium of the platelet and the release reaction , 1972 .

[34]  W. Norde,et al.  Why proteins prefer interfaces. , 1991, Journal of biomaterials science. Polymer edition.

[35]  S. Wilson,et al.  Effect of Coacervated α-Elastin on Proliferation of Vascular Smooth Muscle and Endothelial Cells , 1998 .

[36]  M. Sefton,et al.  Platelet activation in whole blood by artificial surfaces: identification of platelet-derived microparticles and activated platelet binding to leukocytes as material-induced activation events. , 1995, The Journal of laboratory and clinical medicine.