It is still an open challenge to find a biodegradable metallic material exhibiting sufficient mechanical properties and degradation behavior to serve as an arterial stent. In this study, Zn-Mg alloys of 0.002 (Zn-002Mg), 0.005 (Zn-005Mg) and 0.08wt% Mg (Zn-08Mg) content were cast, extruded and drawn to 0.25mm diameter, and evaluated as potential biodegradable stent materials. Structural analysis confirmed formation of MgZn intermetallic in all three alloys with the average grain size decreasing with increasing Mg content. Tensile testing, fractography analysis and micro hardness measurements showed the best integration of strength, ductility and hardness for the Zn-08Mg alloy. Yield strength, tensile strength, and elongation to failure values of >200-300MPa, >300-400MPa, and >30% respectively, were recorded for Zn-08Mg. This metal appears to be the first formulated biodegradable material that satisfies benchmark values desirable for endovascular stenting. Unfortunately, the alloy reveals signs of age hardening and strain rate sensitivity, which need to be addressed before using this metal for stenting. The explants of Zn-08Mg alloy residing in the abdominal aorta of adult male Sprague-Dawley rats for 1.5, 3, 4.5, 6 and 11months demonstrated similar, yet slightly elevated inflammation and neointimal activation for the alloy relative to what was recently reported for pure zinc.
Nitric
oxide (NO) is a highly potent but short-lived endogenous radical with
a wide spectrum of physiological activities. In this work, we developed
an enzymatic approach to the site-specific synthesis of NO mediated
by biocatalytic surface coatings. Multilayered polyelectrolyte films
were optimized as host compartments for the immobilized β-galactosidase
(β-Gal) enzyme through a screen of eight polycations and eight
polyanions. The lead composition was used to achieve localized production
of NO through the addition of β-Gal–NONOate, a prodrug
that releases NO following enzymatic bioconversion. The resulting
coatings afforded physiologically relevant flux of NO matching that
of the healthy human endothelium. The antiproliferative effect due
to the synthesized NO in cell culture was site-specific: within a
multiwell dish with freely shared media and nutrients, a 10-fold inhibition
of cell growth was achieved on top of the biocatalytic coatings compared
to the immediately adjacent enzyme-free microwells. The physiological
effect of NO produced via the enzyme prodrug therapy was validated
ex vivo in isolated arteries through the measurement of vasodilation.
Biocatalytic coatings were deposited on wires produced using alloys
used in clinical practice and successfully mediated a NONOate concentration-dependent
vasodilation in the small arteries of rats. The results of this study
present an exciting opportunity to manufacture implantable biomaterials
with physiological responses controlled to the desired level for personalized
treatment.
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