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

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.

Blood compatible materials: state of the art

“…These include gold-thiol reactions 151 and isocyanate-hydroxyl reactions 153 to attach PEO to the substrate, and N-hydroxysuccinimide (NHS)-hydroxyl reactions to attach ATH to the distal end of the PEO. 154 These ATH-PEO surfaces showed improved antithrombotic activity (antithrombin binding, factor Xa inhibition, prolonged clotting time, reduced platelet adhesion). Interestingly it was found that the protein This journal is © The Royal Society of Chemistry 2014 resistance of the PEO was not diminished by the closely adjacent ATH.…”

“…We have developed ATH as a surface modier using gold, 151,152 polyurethane 153,154 and PDMS 155 as substrates. The ATH was attached to these substrates using PEO as a spacer and for protein resistance.…”

Thermoplastic polyurethane surface coated with polymer brushes for reduced protein and cell attachment

“…11,12 There are numerous reports on polyurethane surface modification for decreased protein adsorption and cell adhesion. [13][14][15][16][17][18][19][20][21][22][23][24] Some are focused on making entire hydrophilic or amphiphilic polyurethane polymers before forming a medical device 24 but some are focused on surface modification of the formed medical device. [13][14][15][16][17][18][19][20][21][22][23] Generally speaking, interface between medical implant device and body fluid or tissue play a key role in biocompatibility of medical device.…”

Surface modification of polyurethane with a hydrophilic, antibacterial polymer for improved antifouling and antibacterial function

“…15 There are many reports on modification of polyurethane for reduced protein adsorption and cell adhesion. [16][17][18][19][20][21][22][23][24][25][26][27][28] Some are focused on making entire hydrophilic or amphiphilic polyurethane polymers before forming a medical device 28 but some are focused on surface modification of the polyurethane formed medical device. [16][17][18][19][20][21][22][23][24][25][26][27] Regarding bacterial infection prevention, currently, there exist three strategies in developing antibacterial surfaces.…”