Nitric Oxide-Releasing Glucose Biosensors

描述(申请人提供)：这项建议的目的是探索使用新型的NO释放传感膜来开发改进的皮下葡萄糖生物传感器，使其在体内发挥更可靠的作用。利用局部NO释放来提高体内皮下传感器的性能的概念代表了一种新的方法，它可能会克服阻碍体内生物传感器发展的关键障碍，这些障碍一旦植入患者体内就能可靠地发挥作用。目前关于NO在血管生成、吞噬、血栓形成和伤口愈合中的作用的科学知识表明，在传感器界面上受控释放NO可能会增加流向传感器的血流量，减少炎症，并通过抑制细菌黏附和最小化后续包膜的厚度来促进伤口愈合。因此，良好的生物相容性可以最大限度地减少宿主的生理反应，从而使目前的皮下生物传感器的体内性能得到显著改善。在合成了具有足够的分析物渗透性和广泛的NO释放特性(包括通量和持续时间)的NO释放传感膜之后，我们将：1)作为NO释放特性的函数在体内评估此类材料的组织生物相容性；2)制备功能性NO释放葡萄糖微传感器；3)在猪模型中评估此类传感器的体内分析性能。这项拟议的研究有可能导致植入式葡萄糖传感器的出现，减少生物污垢和细菌感染，促进伤口愈合，并改善分析性能。具有这些特性的功能性血糖传感器将影响数百万糖尿病患者，他们是连续血糖监测设备的潜在候选者。这项建议的目的是探索使用新型的一氧化氮(NO)释放传感器膜来开发改进的皮下葡萄糖生物传感器，使其在体内发挥更可靠的作用。这项拟议的研究有可能导致植入式葡萄糖传感器的出现，减少生物污垢和细菌感染，促进伤口愈合，并改善分析性能。

DESCRIPTION (provided by applicant): The objective of this proposal is to explore the use of novel NO releasing sensor membranes for developing improved subcutaneous glucose biosensors that function more reliably in vivo. The concept of using local NO release to enhance the performance of in vivo subcutaneous sensors represents a novel approach that may overcome the key obstacles that have prevented the development of in vivo biosensors that function reliably once implanted in patients. Current scientific knowledge regarding the role of NO in angiogenesis, phagocytosis, thrombosis, and wound healing suggests that the controlled release of NO at a sensor interface may increase blood flow to the sensor, reduce inflammation, and promote wound healing by inhibiting bacterial adhesion and minimizing the thickness of the ensuing capsule. Favorable biocompatibility thus may minimize host physiological responses such that the in vivo performance of current subcutaneous biosensors would be dramatically improved. Following the synthesis of NO-releasing sensor membranes with adequate analyte permeability and a wide range of NO release characteristics including flux and duration, we will: 1) evaluate the tissue biocompatibility of such materials in vivo as a function of NO release properties; 2) fabricate functional NO-releasing glucose microsensors; 3) evaluate the in vivo analytical performance of such sensors in a pig model. The proposed research has the potential to lead to implantable glucose sensors that exhibit reduced biofouling and bacterial infection, enhanced wound healing, and improved analytical performance. A functional glucose sensor with these characteristics would impact millions of diabetic patients who are potential candidates for continuous glucose monitoring devices. PUBLIC HEALTH RELEVANCE The objective of this proposal is to explore the use of novel nitric oxide (NO)-releasing sensor membranes for developing improved subcutaneous glucose biosensors that function more reliably in vivo. The proposed research has the potential to lead to implantable glucose sensors that exhibit reduced biofouling and bacterial infection, enhanced wound healing, and improved analytical performance.