Polyurethane modified with an antithrombin-heparin complex via polyethylene oxide linker/spacers: influence of PEO molecular weight and PEO-ATH bond on catalytic and direct anticoagulant functions.
A segmented polyurethane (PU) was modified with polyethylene oxides (PEO) of varying molecular weight and end group. The PEO served as linker/spacers to immobilize an antithrombin-heparin (ATH) anticoagulant complex on the PU. Isocyanate groups were introduced into the PU to enable attachment of either "conventional" homo-bifunctional dihydroxy-PEO (PEO-OH surface) or a hetero-bifunctional amino-carboxy-PEO (PEO-COOH surface). The PEO surfaces were functionalized with N-hydroxysuccinimide (NHS) groups using appropriate chemistries, and ATH was attached to the distal NHS end of the PEO (PEO-OH-ATH and PEO-COOH-ATH surfaces). Water contact angle and fibrinogen adsorption measurements showed increased hydrophilicity and reduced fibrinogen adsorption from buffer on all PEO surfaces compared to unmodified PU. ATH uptake on NHS-functionalized PEO was quantified by radiolabeling. Despite the different PEO molecular weights and end groups, and NHS-functionalization chemistries, the surface densities of ATH were similar. The adsorption of fibrinogen and antithrombin (AT) from plasma was measured in a single experiment using dual radiolabeling. On PEO-ATH surfaces fibrinogen adsorption was minimal while AT adsorption was high showing the selectivity of the heparin moiety of ATH for AT. The PEO-COOH-ATH surfaces showed slightly greater AT adsorption than the PEO-OH-ATH surfaces. Thrombin adsorption on all of the PEO-ATH surfaces was greater than on the corresponding PEO surfaces without ATH, and was highest on the PEO-OH-ATH, suggesting potential anticoagulant properties for this surface via direct thrombin inhibition by the AT portion of ATH.
School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada.
Kyla N
KN
Sask
Leslie R
LR
Berry
Anthony K C
AK
Chan
John L
JL
Brash
D000327:Adsorption / Q000187:drug effects; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology*; D002384:Catalysis / Q000187:drug effects; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects; D013499:Surface Properties / Q000187:drug effects; D014867:Water / Q000737:chemistry
D000925:Anticoagulants; D000991:Antithrombins; D011140:Polyurethanes; D014867:Water; D011092:Polyethylene Glycols; D005340:Fibrinogen; D006493:Heparin