Improving the hemocompatibility of hydrophobic polymers via nitric oxide release: In vivo evaluation of nitric oxide-releasing silicone rubbers and the development of S-nitrosothiol derivatized polymer fillers.

摘要

Polymeric materials used to coat or construct biomedical devices universally inspire a foreign body response when in contact with a biological system (e.g., thrombus formation on the polymer surface when in contact with blood). Nitric oxide (NO) has been shown to have a number of physiological functions, including serving as a potent inhibitor of platelet adhesion and activation. In this work, intravascular amperometric oxygen sensors were coated with NO-releasing silicone rubber films and evaluated in porcine femoral and carotid arteries for improved hemocompatibility and analytical performance. It was demonstrated that a surface flux of NO in the range of 1--10 x 10-10 mol·m-2·min-1 from the implanted NO-releasing sensors showed no statistically significant difference in measured blood oxygen levels when compared to standard discrete blood gas analysis over a 15--16 h period (p ≤ 0.05), while non-NO-releasing control sensors implanted in the same animals had a statistically significant difference in measured blood oxygen after 10 h (p ≤ 0.05). The use of the NO-release coatings also completely eliminated gross thrombus formation on the sensor surfaces.; A new type of NO-releasing material was also developed. Three different S-nitrosothiols (S-ntirosocysteine (NO-Cys), S-nitroso-N-acetylcysteine (SNAG) and S-nitroso-N-acetylpenicillamine (SNAP)), were covalently tethered to the surface of fumed silica polymer filler particles (FS). Derivatized particles were blended into plasticized polyurethane and crosslinked silicone rubber films. The NO-release properties from these cured polymer films were characterized in response to copper ions, ascorbate and photoinitiated NO generation. Surface fluxes via photoinitiated NO-release in the range of 0--7.5 x 10 -10 mol·cm-2·min-1 were achieved from 20 wt% SNAP-FS in releasing silicone rubber irradiated with 0--100 W visible light. This is the first example of an NO-releasing hydrophobic polymer with an external on/off trigger that shows completely reversible and controllable NO generation based on the duration and intensity of light irradiating the material.