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

J Biomed Mater Res A. 2012 Oct;100(10):2821-8. doi: 10.1002/jbm.a.34218. Epub 2012 May 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption / drug effects
  • Anticoagulants / pharmacology*
  • Antithrombins / pharmacology*
  • Catalysis / drug effects
  • Fibrinogen / metabolism
  • Heparin / metabolism
  • Heparin / pharmacology*
  • Humans
  • Molecular Weight
  • Polyethylene Glycols / chemistry*
  • Polyurethanes / chemistry*
  • Protein Binding / drug effects
  • Surface Properties / drug effects
  • Water / chemistry

Substances

  • Anticoagulants
  • Antithrombins
  • Polyurethanes
  • Water
  • Polyethylene Glycols
  • Fibrinogen
  • Heparin