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Nitric oxide-generating silicone as a blood-contacting biomaterial.
Coagulation upon blood-contacting biomaterials remains a problem for short- and long-term clinical applications. This study examined the ability of copper(II)-doped silicone surfaces to generate nitric oxide (NO) and locally inhibit coagulation. Silicone was doped with 3-μm copper [Cu(0)] particles yielding 3 to 10 weight percent (wt%) Cu in 70-μm thick Cu/silicone polymeric matrix composites (Cu/Si PMCs). At 3, 5, 8, and 10 wt% Cu doping, the surface expression of Cu was 12.1% ± 2.8%, 19.7% ± 5.4%, 29.0% ± 3.8%, and 33.8% ± 6.5%, respectively. After oxidizing Cu(0) to Cu(II) by spontaneous corrosion, NO flux, J(NO) (mol · cm(-2) · min(-1)), as measured by chemiluminescence, increased with surface Cu expression according to the relationship J(NO) = (1.63%SA(Cu) - 0.81) × 10(-11), R(2) = 0.98, where %SA(Cu) is the percentage of surface occupied by Cu. NO flux at 10 wt% Cu was 5.35 ± 0.74 × 10(-10) mol · cm(-2) · min(-1). The clotting time of sheep blood exposed to these surfaces was 80 ± 13 seconds with pure silicone and 339 ± 44 seconds when 10 wt% Cu(II) was added. Scanning electron microscopies (SEMs) of coatings showed clots occurred away from exposed Cu dendrites. In conclusion, Cu/Si PMCs inhibit coagulation in a dose-dependent fashion related to the extent of copper exposure on the coated surface.