title: Modification of polyurethane surface with an antithrombin-heparin complex for blood contact: influence of molecular weight of polyethylene oxide used as a linker/spacer.
abstract: Polyurethane (PU) was modified using isocyanate chemistry to graft polyethylene oxide (PEO) of various molecular weights (range 300-4600). An antithrombin-heparin (ATH) covalent complex was subsequently attached to the free PEO chain ends, which had been functionalized with N-hydroxysuccinimide (NHS) groups. Surfaces were characterized by water contact angle and X-ray photoelectron spectroscopy (XPS) to confirm the modifications. Adsorption of fibrinogen from buffer was found to decrease by ~80% for the PEO-modified surfaces compared to the unmodified PU. The surfaces with ATH attached to the distal chain end of the grafted PEO were equally protein resistant, and when the data were normalized to the ATH surface density, PEO in the lower MW range showed greater protein resistance. Western blots of proteins eluted from the surfaces after plasma contact confirmed these trends. The uptake of ATH on the PEO-modified surfaces was greatest for the PEO of lower MW (300 and 600), and antithrombin binding from plasma (an indicator of heparin anticoagulant activity) was highest for these same surfaces. The PEO-ATH- and PEO-modified surfaces also showed low platelet adhesion from flowing whole blood. It is concluded that for the PEO-ATH surfaces, PEO in the low MW range, specifically MW 600, may be optimal for achieving an appropriate balance between resistance to nonspecific protein adsorption and the ability to take up ATH and bind antithrombin in subsequent blood contact.
authors.affiliation: School of Biomedical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
authors.forename: Kyla N
authors.initials: KN
authors.lastname: Sask
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Berry
authors.forename: Anthony K C
authors.initials: AK
authors.lastname: Chan
authors.forename: John L
authors.initials: JL
authors.lastname: Brash
mesh_terms: D000327:Adsorption; D000991:Antithrombins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D005340:Fibrinogen / Q000737:chemistry; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D000991:Antithrombins; D011140:Polyurethanes; D014867:Water; D011092:Polyethylene Glycols; D005340:Fibrinogen; D006493:Heparin