title: Whole blood coagulation on protein adsorption-resistant PEG and peptide functionalised PEG-coated titanium surfaces.
abstract: The aim of this study was to investigate whole blood coagulation on low blood plasma protein adsorbing surfaces. For this purpose, the polycationic graft copolymer poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), PLL-g-PEG grafted with a cell adhesive peptide containing the amino acid sequence -Arg-Gly-Asp- (RGD), and PLL-g-PEG with a control peptide -Arg-Asp-Gly- (RDG) were adsorbed onto titanium (oxide), forming stable monomolecular adlayers through electrostatic attraction. Free oscillation rheometry and complementary techniques were used to measure the coagulation time (CT) and other interactions of the surfaces with native whole blood, recalcified platelet-rich plasma (PRP), and recalcified citrated platelet-free plasma (PFP). The results show that the uncoated titanium surfaces (reference) activated platelets and quickly triggered the coagulation cascade via the intrinsic pathway, whereas the PLL-g-PEG surfaces displayed a prolonged CT, approximately 2-3 times longer compared to uncoated titanium. We hypothesise that blood coagulates outside the vascular system independent of low protein adsorption to or activation by surfaces, due to the absence of an active down-regulation of procoagulative processes by the vascular endothelium.
authors.affiliation: Astra Zeneca R&D, Mölndal, SE-431 83 Göteborg, Sweden. kenny.m.hansson@astrazeneca.com
authors.forename: Kenny M
authors.initials: KM
authors.lastname: Hansson
authors.forename: Samuele
authors.initials: S
authors.lastname: Tosatti
authors.forename: Joakim
authors.initials: J
authors.lastname: Isaksson
authors.forename: Jonas
authors.initials: J
authors.lastname: Wetterö
authors.forename: Marcus
authors.initials: M
authors.lastname: Textor
authors.forename: Tomas L
authors.initials: TL
authors.lastname: Lindahl
authors.forename: Pentti
authors.initials: P
authors.lastname: Tengvall
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets; D020099:Coated Materials, Biocompatible; D005434:Flow Cytometry; D006801:Humans; D007773:Lactates; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014025:Titanium
chemical_list: D020099:Coated Materials, Biocompatible; D007773:Lactates; D009842:Oligopeptides; D011506:Proteins; C088513:poly(lactic acid-ethylene glycol); C009495:titanium dioxide; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D014025:Titanium