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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
Author(s) -
Sask Kyla N.,
Berry Leslie R.,
Chan Anthony K. C.,
Brash John L.
Publication year - 2012
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34218
Subject(s) - antithrombin , adsorption , polymer chemistry , materials science , surface modification , isocyanate , bifunctional , polyurethane , linker , polymer , chemistry , organic chemistry , heparin , catalysis , biochemistry , composite material , computer science , operating system
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. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2821–2828, 2012.