Biomedical Engineering Reference
In-Depth Information
monomer group on the end. Catheters were heated in aqueous solutions of modifi ed ATH and trace
Triton X-114 surfactant so that radical-initiated polymerization of base coat and ATH spacer end
groups could take place at the catheter surface. The resultant products had coatings of polymerized
base coats with covalently incorporated PEO-linked ATH covering the polyurethane catheter sup-
port. A few experiments utilizing covalent link points to the catheter itself were achieved by fi rst
reacting N-atoms in urethane-urea groups on the catheter surfaces with isocyanate monomers at
high temperature. Mainly, the vast majority of experiments omitted this direct covalent linkage to the
catheter surface. Detailed physicochemical and activity measurements were performed on all sur-
faces. Fluorescence immunohistochemical analysis confi rmed fairly uniform fi lms of AT-containing
product on the ATH-coated surfaces. 305 Surface tension calculated from contact angle measurements
revealed that while both uncoated and heparin-coated polyurethane catheters were hydrophobic in
nature, ATH-coated surfaces displayed a signifi cant net hydrophilicity. 303 This hydrophilic character
was considered more compatible with the aqueous systemic environment in vivo . 303 Determination of
graft density in ATH coatings by use of radiolabeled ATH gave values in freshly prepared products
of 26 pmol cm 2 . 304 Coating stability was examined by several consecutive saline washes using a
roller pump. Under this shear stress, ATH surface density was rapidly reduced to a plateau level of
12 pmol cm - 2 . However, a large proportion of the remaining ATH coating showed remarkable stabil-
ity as roller pump washing with several treatments of a potent general protease only lowered ATH
levels to around 7 pmol cm - 2 . 304 Functional activity comparisons showed that ATH surfaces had
6.8 times the anti-FXa catalytic activity relative to commercial heparin-coated catheters 303 and uptake
of AT from plasma was signifi cantly greater (
twofold) for ATH than heparin coatings. 305 Finally,
a survey of binding by various proteins after incubation of the catheters in plasma determined that,
while both heparin and ATH (but not uncoated polyurethane) catheters bound signifi cant amounts
of AT, adsorption of other plasma proteins was much reduced for ATH. 305 In summary, many of the
desirable in vitro characteristics for blood compatibility (high-coating density, stability, anticoagulant
activity and low-protein binding) were embodied in surfaces with Chan et al. ATH covalently linked
to a polymer base coat adherent to polyurethane catheters.
18.6.2 I N V IVO P ERFORMANCE
Surfaces coated with Chan et al. ATH that had been extensively characterized in vitro were studied
in a number of animal models. In particular, attention was given to the assessment of resistance
to induction of clot formation as well as fi brin(ogen) accretion. The overall marker of effective
value for coated devices within the vasculature was the ability to remain patent so that fl ow could
continue to organ sites.
Endoluminal grafts covalently coated with Schiff base-Amadori ATH were compared to
other direct thrombin inhibitors in a rabbit jugular vein model. 296 After coating, grafts (2 cm
in length) were inserted within jugular vein segments and normal blood fl ow allowed to con-
tinue in the anesthetized animal for a 3 h period. At the end of this period, grafts were carefully
explanted and rinsed. Weight of clot formed on the graft and accretion of labeled fi brin (from
radiolabeled fi brinogen injected at onset of the experiment) were measured. This is considered
a particularly harsh model for the coagulant system since rabbits do not take anesthesia well
for prolonged periods. 296 Results from coating comparisons were dramatic. Surfaces coated with
ATH showed signifi cantly reduced clot masses than those on AT or hirudin-coated grafts. 296 Even
more striking were the decreases in fi brin accreted on ATH explants compared to that of hirudin
or nontreated controls. The possibility that surface activation and application of the active-linking
agent to the graft may somehow have played a role in ATH biocompatibility was ruled out since
similar experiments with grafts treated with the activator (NaOCl), initiator (Na 2 S 2 O 4 ), and
linker (allyl glycidyl ether), but not ATH led to measurably increased clot formation relative to
ATH surfaces. 296 Examination of plasma from samples taken over time gave further evidence
of differences in large-scale activation of the coagulation cascade since there was a trend for
 
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