Biocompatible Chemical Sensors via Nitric Oxide Release

到目前为止，开发用于临床实时监测血气的体内化学传感器的努力， 危重病人和糖尿病患者的电解质、葡萄糖等受到不可靠分析的阻碍 由于传感器植入引起的生物相容性问题(细胞黏附、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成分 制造具有外层聚合物涂层的体内化学传感器，该涂层可缓慢释放或产生低水平的 一氧化氮(NO)。NO的局部释放/生成有望极大地提高生物相容性 植入的传感器，从而产生更可靠和临床有用的分析数据。来自阶段的结果 I和II研究清楚地表明，原位释放NO显著减少表面血栓的形成 大大提高了血管内氧传感器的活体分析精度。最近的数据现在也 提示局部NO释放可能有益于放置在皮下的传感器的性能(例如， 葡萄糖传感器)通过减少周围组织的炎症反应。在第三阶段研究中， 血管内氧传感器的持续生物兼容性/分析性能测试 提出了最有前景/最优化的基于重氮双二醇的NO释放聚合物涂层(在猪中 模型)，以更好地了解实现减少血小板黏附/激活所需的NO的准确水平 在传感器的表面上，并伴随着分析性能的提高。对于更长期的传感器 植入物，一种在设备表面局部产生NO的全新策略将被探索。 具有固定化铜离子中心的新型聚合物涂层将被开发用于催化 用于原位转化内源亚硝基硫醇物种(RSNO)的表面(例如，亚硝基谷胱甘肽， 亚硝基半胱氨酸等。)到NO，从而在地表局部提供持续的NO物种的产生 植入的装置。用这些新型铜基材料制备功能性血管内氧传感器 涂层将被制造并测试抗凝血性以及体内分析的准确性。在……里面 此外，还将进行实验，以评估反应性RSNO水平的相对变化 电化学一氧化氮传感器在血液(猪)和皮下液体(大鼠)中的底物 铜离子基涂层。到目前为止，为活体传感器开发的各种聚合物材料 也被证明作为其他生物医学设备的涂层很有用，在这些设备中，抗血栓表面严重 (例如，血管移植、体外循环、血液过滤器等)。因此，这一事件的总体影响 对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.