Biocompatible Chemical Sensors via Nitric Oxide Release

因此，开发用于实时临床监测血气的体内化学传感器的努力， 电解质、葡萄糖等在危重病和糖尿病患者中的应用一直受到不可靠的分析方法的阻碍。 由于传感器植入引起的生物相容性问题（细胞粘附，血栓， 炎症反应等）。这项研究的目标是探索和优化所需的化学物质， 制造具有外部聚合物涂层的体内化学传感器，该外部聚合物涂层缓慢释放或产生低水平的 一氧化氮（NO）。预期NO的局部释放/产生将大大增强生物相容性。 植入的传感器，从而产生更可靠和临床有用的分析数据。阶段结果 I & II研究清楚地表明，原位释放NO显著减少表面血栓形成 大大提高了血管内氧传感器的体内分析精度。最近的数据也 表明局部NO释放可能有益于皮下放置的传感器的性能（例如， 葡萄糖传感器）通过减少周围组织的炎症反应。在III期研究中， 血管内氧传感器的连续生物相容性/分析性能测试， 提出了最有前景/最优化的基于二醇二氮烯鎓的NO释放聚合物涂层（在猪中 模型）以更好地理解实现血小板粘附/活化降低所需的NO的精确水平 传感器的表面和分析性能的相应改进。对于长期传感器 植入物，一个全新的策略，以产生NO局部的装置的表面将被探索。 具有固定化铜离子位点的新型聚合物涂层将被开发用于催化 用于内源性亚硝基硫醇物质（RSNO）原位转化的表面（例如，亚硝基谷胱甘肽， 亚硝基半胱氨酸等）从而在表面局部地提供NO物质的持续产生 植入的设备。用这些新的铜基材料制备的功能性血管内氧传感器 将制造涂层并测试抗血栓性和体内分析精度。在 此外，还将进行实验，以评估反应性RSNO水平的相对变化 在血液（猪）和皮下液体（大鼠）中使用涂覆有 铜离子基涂层。各种聚合物！迄今为止开发的用于体内传感器的材料 也被证明可用作抗血栓表面严重 需要（例如，血管移植物、体外回路、血液过滤器等）。因此，这一事件的总体影响 医学的研究是相当广泛和重要的。

Heretofore, efforts to develop in vivo chemical sensors for real-time clinical monitoring of blood gases, electrolytes, glucose, etc. in critically ill and diabetic patients have been stymied by the unreliable analytical results obtained owing to biocompatibility problems induced by sensor implantation (cell adhesion, thrombus, inflammatory response, etc.). The goal of this research is to explore and optimize the chemistries required to fabricate in vivo chemical sensors with outer polymeric coatings that slowly release or generate low levels of nitric oxide (NO). The local release/generation of NO is expected to greatly enhance the biocompatibility of the implanted sensors, thereby yielding more reliable and clinically useful analytical data. Results from Phase I & II studies clearly demonstrate that in-situ release of NO significantly reduces surface thrombusformation and greatly improves in the in vivo analytical accuracy of intravascular oxygen sensors. Recent data now also suggest that local NO release may be beneficial to the performance of sensors placed subcutaneously (e.g., glucose sensors) by reducing the inflammatory response of the surrounding tissue. In Phase III studies, continued biocompatibility/analytical performance testing of intravascular oxygen sensors prepared with the most promising/optimized diazeniumdiolate-based NO releasing polymeric coatings are proposed (in porcine model) to better understand the precise levels of NO required to achieve reduced platelet adhesion/activation on the sensors' surface and a concomitant improvement in analytical performance. For longer-term sensor implants, a completely new strategy to generate NO locally at the surface of the devices will be explored. New polymeric coatings that possess immobilized copper ion sites will be developed to serve as catalytic surfaces for in situ conversion of endogenous nitrosothiol species (RSNO) (e.g., nitrosoglutathione, nitrosocysteine, etc.) to NO, thereby providing sustained generation of the NO species, locally, at the surface of the implanted device. Functional intravascular oxygen sensors prepared with these new copper-based coatings will be fabricated and tested for thromboresistivity as weir as in vivo analytical accuracy. In addition, experiments will be undertaken to assess the relative variations in the levels of reactive RSNO substrates in both blood (pigs) and subcutaneous fluid (rats) using electrochemical NO sensors coated with the copper ion-based coatings. The various polymeric!materials developed thus far for in vivo sensors have also proven useful as coatings for other biomedical devices in which thromboresistant surfaces are sorely needed (e.g., vascular grafts, extracorporeal circuits, blood filters, etc.). Hence, the overall impact of this research on medicine is quite broad and significant.