title: The influence of surface chemistry on adsorbed fibrinogen conformation, orientation, fiber formation and platelet adhesion.
abstract: Thrombosis is a clear risk when any foreign material is in contact with the bloodstream. Here we propose an immunohistological stain-based model for non-enzymatic clot formation that enables a facile screen for the thrombogenicity of blood-contacting materials. We exposed polymers with different surface chemistries to protease-free human fibrinogen. We observed that on hydrophilic surfaces, fibrinogen is adsorbed via αC regions, while the γ400-411 platelet-binding dodecapeptide on the D region becomes exposed, and fibrinogen fibers do not form. In contrast, fibrinogen is adsorbed on hydrophobic surfaces via the relatively hydrophobic D and E regions, exposing the αC regions while rendering the γ400-411 inaccessible. Fibrinogen adsorbed on hydrophobic surfaces is thus able to recruit other fibrinogen molecules through αC regions and polymerize into large fibrinogen fibers, similar to those formed in vivo in the presence of thrombin. Moreover, the γ400-411 is available only on the large fibers not elsewhere throughout the hydrophobic surface after fibrinogen fiber formation. When these surfaces were exposed to gel-sieved platelets or platelet rich plasma, a uniform monolayer of platelets, which appeared to be activated, was observed on the hydrophilic surfaces. In contrast, large agglomerates of platelets were clustered on fibers on the hydrophobic surfaces, resembling small nucleating thrombi. Endothelial cells were also able to adhere to the monomeric coating of fibrinogen on hydrophobic surfaces. These observations reveal that the extent and type of fibrinogen adsorption, as well as the propensity of adsorbed fibrinogen to bind platelets, may be modulated by careful selection of surface chemistry.
  
  
  
  Thrombosis is a well-known side effect of the introduction of foreign materials into the bloodstream, as might exist in medical devices including but not limited to stents, valves, and intravascular catheters. Despite many reported studies, the body's response to foreign materials in contact with the blood remains poorly understood. Current preventive methods consist of drug eluting coatings on the devices or the systemic administration of standard anticoagulants. Here we present a potential mechanism by which surface chemistry can affects fibrinogen conformation and thus affects platelet adhesion and consequently thrombus formation. Our findings suggest a possible coating which enables endothelial cell adhesion while preventing platelet adhesion.
authors.affiliation: Department of Materials Science and Engineering, Stony Brook University, Stony Brook, NY 11794, USA; Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20903, USA. Electronic address: liudi@suda.edu.cn.
authors.forename: Liudi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20903, USA. Electronic address: Brendan.Casey@fda.hhs.gov.
authors.forename: Brendan
authors.initials: B
authors.lastname: Casey
authors.affiliation: Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: dennis.galanakis@stonybrookmedicine.edu.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Galanakis
authors.affiliation: Department of Materials Science and Engineering, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: clement.marmorat@gmail.com.
authors.forename: Clement
authors.initials: C
authors.lastname: Marmorat
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20903, USA. Electronic address: Shelby.Skoog@fda.hhs.gov.
authors.forename: Shelby
authors.initials: S
authors.lastname: Skoog
authors.affiliation: Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20903, USA. Electronic address: Katherine.Vorvolakos@fda.hhs.gov.
authors.forename: Katherine
authors.initials: K
authors.lastname: Vorvolakos
authors.affiliation: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: Marcia.Simon@stonybrookmedicine.edu.
authors.forename: Marcia
authors.initials: M
authors.lastname: Simon
authors.affiliation: Department of Materials Science and Engineering, Stony Brook University, Stony Brook, NY 11794, USA; Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20903, USA. Electronic address: miriam.rafailovich@stonybrook.edu.
authors.forename: Miriam H
authors.initials: MH
authors.lastname: Rafailovich
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009842:Oligopeptides / Q000737:chemistry*; D010973:Platelet Adhesiveness; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D005337:Fibrin; D005340:Fibrinogen
keywords: Fibrinogen; Fibrinogen adsorption; Non-thrombogenic surface; Platelets adhesion; Thrombosis