title: Direct thrombin inhibitor-bivalirudin functionalized plasma polymerized allylamine coating for improved biocompatibility of vascular devices.
abstract: The direct thrombin inhibitor of bivalirudin (BVLD), a short peptide derived from hirudin, has drawn an increasing attention in clinical application because it is safer and more effective than heparin for diabetic patients with moderate- or high-risk for acute coronary syndromes (ACS). In this study, BVLD was covalently conjugated on plasma polymerized allylamine (PPAam) coated 316L stainless steel (SS) to develop an anticoagulant surface. QCM-D real time monitoring result shows that 565±20 ng/cm2 of BVLD was bound to the PPAam surface. Infrared spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) confirmed the immobilization of BVLD. The conjugation of BVLD onto the PPAam coating led to enhanced binding of thrombin, and the activity of the thrombin adsorbed on its surface was effectively inhibited. As a result, the BVLD immobilized PPAam (BVLD-PPAam) substrate prolonged the clotting times, and exhibited inhibition in adhesion and activation of platelets and fibrinogen. We also found that the BVLD-PPAam coating significantly enhanced endothelial cell adhesion, proliferation, migration and release of nitric oxide (NO) and secretion of prostaglandin I2 (PGI2). In vivo results indicate that the BVLD-PPAam surface restrained thrombus formation by rapidly growing a homogeneous and intact endothelium on its surface. These data suggest the potential of this multifunctional BVLD-PPAam coating for the application not only in general vascular devices such as catheters, tubes, oxygenator, hemodialysis membranes but also vascular grafts and stents.
authors.affiliation: Key Laboratory of Advanced Technology for Materials of Education Ministry, The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031, China.
authors.forename: Zhilu
authors.initials: Z
authors.lastname: Yang
authors.forename: Qiufen
authors.initials: Q
authors.lastname: Tu
authors.forename: Manfred F
authors.initials: MF
authors.lastname: Maitz
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Huang
mesh_terms: D000499:Allylamine / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000991:Antithrombins / Q000737:chemistry* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D004285:Dogs; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006629:Hirudins / Q000737:chemistry* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D058105:Polymerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013193:Stainless Steel / Q000737:chemistry*; D013499:Surface Properties; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000991:Antithrombins; D020099:Coated Materials, Biocompatible; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013193:Stainless Steel; D000499:Allylamine; D013917:Thrombin; C074619:bivalirudin