title: Plasma functionalization of polycarbonaturethane to improve endothelialization--Effect of shear stress as a critical factor for biocompatibility control.
abstract: Medical devices made of polycarbonaturethane (PCU) combine excellent mechanical properties and little biological degradation, but restricted hemocompatibility. Modifications of PCU might reduce platelet adhesion and promote stable endothelialization. PCU was modified using gas plasma treatment, binding of hydrogels, and coupling of cell-active molecules (modified heparin, anti-thrombin III (ATIII), argatroban, fibronectin, laminin-nonapeptide, peptides with integrin-binding arginine-glycine-aspartic acid (RGD) motif). Biocompatibility was verified with static and dynamic cell culture techniques. Blinded analysis focused on improvement in endothelial cell (EC) adhesion/proliferation, anti-thrombogenicity, reproducible manufacturing process, and shear stress tolerance of ECs. EC adhesion and antithrombogenicity were achieved with 9/35 modifications. Additionally, 6/9 stimulated EC proliferation and 3/6 modification processes were highly reproducible for endothelialization. The latter modifications comprised immobilization of ATIII (A), polyethyleneglycole-diamine-hydrogel (E) and polyethylenimine-hydrogel connected with modified heparin (IH). Under sheer stress, only the IH modification improved EC adhesion within the graft. However, ECs did not arrange in flow direction and cell anchorage was restricted. Despite large variation in surface modification chemistry and improved EC adhesion under static culture conditions, additional introduction of shear stress foiled promising preliminary data. Therefore, biocompatibility testing required not only static tests but also usage of physiological conditions such as shear stress in the case of vascular grafts.
authors.affiliation: IMHR, Institute for Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Lukas
authors.affiliation: Dualis Medtech GmbH, Seefeld, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thomas
authors.affiliation: IMHR, Institute for Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Gessner
authors.affiliation: Dualis Medtech GmbH, Seefeld, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wehner
authors.affiliation: Dualis Medtech GmbH, Seefeld, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmid
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Schmid
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany Karla.Lehle@UKR.de.
authors.forename: Karla
authors.initials: K
authors.lastname: Lehle
mesh_terms: D001792:Blood Platelets / Q000166:cytology; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D058626:Plasma Gases / Q000737:chemistry*; D010973:Platelet Adhesiveness; D011140:Polyurethanes / Q000737:chemistry*; D013314:Stress, Mechanical; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D020099:Coated Materials, Biocompatible; D020100:Hydrogels; D058626:Plasma Gases; D011140:Polyurethanes
keywords: Endothelial cell seeding; biocompatibility; hydrogel; plasma treatment; polyurethane; sheer stress; thrombogenicity