The development of reliable in vivo chemical sensors for real-time clinical monitoring of blood gases, electrolytes, glucose, etc. in critically ill and diabetic patients remains a great challenge owing to inherent biocompatibility problems that can cause errant analytical results upon sensor implantation (e.g., cell adhesion, thrombosis, inflammation). Nitric oxide (NO) is a well-known inhibitor of platelet activation and adhesion, and also a potent inhibitor of smooth muscle cell proliferation. In addition, NO mediates inflammatory response and promotes angiogenesis. Polymers that release or generate NO at their surfaces have been shown to exhibit greatly enhanced thromboresistance in vivo when in contact with flowing blood, as well as reduce inflammatory response when placed subcutaneously, and thus have the potential to improve the biocompatibility of implanted chemical sensors. Locally elevated NO levels at the surface of implanted devices can be achieved by using polymers that incorporate NO donor species that can decompose and release NO spontaneously when in contact with physiological fluids, or NO-generating polymers that possess an immobilized catalyst that decompose endogenous S-nitrosothiols to generate NO in situ. The potential use of such NO-releasing/generating materials for preparing in vivo sensors implanted either intravascularly or subcutaneously, is examined in this review.

A novel approach to potentially resolve serious thrombosis issues associated with kidney dialysis (hemodialysis) therapies is described. New water-soluble polymeric nitric oxide (NO) donors, based on the diazeniumdiolated branched poly(ethylenimine)s and their derivatives, are prepared and characterized. These macromolecular NO donors (with up to 4.15 μmol/mg of total NO release) are utilized as additives to the dialysate solution of model dialysis filters. The presence of these species can create a localized increase in NO levels at the high surface area dialysis fiber/blood interface within the hemodialyzers. Nitric oxide is a naturally occurring and potent anti-platelet agent, and is expected to greatly decrease the risk of thrombosis in the dialysis units.

Nitric oxide (NO) is released by endothelial cells that line the inner walls of healthy blood vessels at fluxes ranging from 0.5 x 10(-10) to 4.0 x 10(-10) mol cm(-2) min(-1), and this continuous NO release contributes to the extraordinary thromboresistance of the intact endothelium. To improve the biocompatibility of blood-contacting devices, a biomimetic approach to release/generate NO at polymer/blood interfaces has been pursued recently (with NO donors or NO generating catalysts doped within polymeric coatings) and this concept has been shown to be effective in preventing platelet adhesion/activation via several in vivo animal studies. However, there are no reports to date describing any quantitative in vitro assay to evaluate the blood compatibilities of such NO release/generating polymers with controlled NO fluxes. Such a methodology is desired to provide a preliminary assessment of any new NO-releasing material, in terms of the effectiveness of given NO fluxes and NO donor amounts on platelet activity before the more complex and costly in vivo testing is carried out. In this article, we report the use of a lactate dehydrogenase assay to study in vitro platelet adhesion on such NO-releasing polymer surfaces with varying NO fluxes. Reduced platelet adhesion was found to correlate with increasing NO fluxes. The highest NO flux tested, 7.05 (+/-0.25) x 10(-10) mol cm(-2) min(-1), effectively reduced platelet adhesion to nearly 20% of its original level (from 14.0 (+/-2.1) x 10(5) cells cm(-2) to 2.96 (+/-0.18) x 10(5) cells cm(-2)) compared to the control polymer coating without NO release capability.

Tunable-aspect ratio gold nanorods have been synthesized by a modified seed-mediated synthesis method. Ascorbic acid was employed as a shape controller to induce anisotropic growth, which made the aspect ratio of the synthesized gold nanorods range from 8.5 to 15.6. These nanorods possess tunable longitudinal surface plasmon resonance absorption band, covering a broad near-infrared (NIR) range, from ~ 680 to 1100 nm. When modified with thiol-polyethylene glycol (SH-PEG), the synthesized Au nanorods showed excellent biocompatibility and stability, which foreshadowed the great potential of their NIR application as photoacoustic contrast agent. Due to their adjustable absorbance in the NIR, the synthesized Au nanorods could offer stronger contrast (3.1 times to the control group without contrast agent used) and higher signal-noise ratio values (SNR; 5.6 times to the control group) in photoacoustic imaging, both in vitro and in vivo experiments. Our work presented here not only added some novel Au-based photoacoustic contrast agents but also described a possibility of contrast agent preparation covering the whole biological NIR window.

BACKGROUND:The determination of reference intervals for the concentration of total S-nitrosothiols (RSNOs) in blood is a highly controversial topic, likely because of the inherent instability of these species. Most currently available techniques to quantify RSNOs in blood require considerable sample handling and multiple pretreatment steps during which light exposure is difficult to completely eliminate. We investigated the effect of brief light exposure on the stability of RSNO species in blood during the initial sampling process.