title: Evaluation of the bulk platelet response and fibrinogen interaction to elastin-like polypeptide coatings.
abstract: In this work, we expand on our understanding of the thrombogenicity of coatings prepared with three different recombinant elastin-like polypeptides (ELPs). The bulk platelet response of the ELP coatings was characterized following whole blood contact under physiological shear flow (300 s(-1) ) using flow cytometry. Prolonged exposure to shear flow (1-h) indicated that materials coated with the longer ELP coatings (ELP2 and ELP4) had less bulk platelet activation and microparticle formation than materials coated with the shorter ELP1. Quartz crystal microbalance with dissipation (QCM-D) was used to monitor the binding of the platelet membrane receptor GPIIb/IIIa to ELP-adsorbed fibrinogen (Fg) surfaces. Compared to the shorter ELPs, a lower amount of Fg adsorbed to the ELP4 coated material and ELP4 appeared to form a softer, more structurally flexible coating layer. When Fg was adsorbed to the ELP coated surface it demonstrated an altered binding for GPIIb/IIIa that was inhibited in the presence of an AGDV-containing peptide but not an RGD-containing peptide. Conversely, on the shorter ELP coatings, binding of GPIIb/IIIa to an adsorbed Fg layer was partially inhibited in the presence of an RGD-containing peptide. These results indicate that both the quantity and conformational state of Fg varies when adsorbed to surfaces coated with ELPs of varying sequence length, which may be mediating their platelet response. Collectively, the findings reinforce the applicability of the ELPs as potential thromboresistant coatings, especially with the use of the longer polypeptide-ELP4.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Ontario, Canada.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Srokowski
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Woodhouse
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004549:Elastin / Q000737:chemistry*; D005260:Female; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008297:Male; D008422:Materials Testing; D009842:Oligopeptides / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*
chemical_list: D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D004549:Elastin
keywords: blood compatibility; elastin-like polypeptide; fibrinogen; platelet activation; quartz crystal microbalance with dissipation