Nitric Oxide-Releasing Glucose Biosensors

描述（由申请人提供）：本提案的目的是探索使用新型NO释放传感器膜来开发改进的皮下葡萄糖生物传感器，其在体内更可靠地发挥作用。使用局部NO释放来增强体内皮下传感器的性能的概念代表了一种新的方法，该方法可以克服已经阻止体内生物传感器的发展的关键障碍，所述体内生物传感器一旦植入患者体内就可靠地起作用。目前关于NO在血管生成、吞噬作用、血栓形成和伤口愈合中的作用的科学知识表明，传感器界面处的NO的受控释放可以增加流向传感器的血流，减少炎症，并通过抑制细菌粘附和使随后的囊的厚度最小化来促进伤口愈合。因此，有利的生物相容性可以使宿主生理反应最小化，使得当前皮下生物传感器的体内性能将显著改善。在合成具有足够的分析物渗透性和宽范围的NO释放特性（包括通量和持续时间）的NO释放传感器膜之后，我们将：1）评估这些材料在体内的组织生物相容性作为NO释放特性的函数; 2）制造功能性NO释放葡萄糖微传感器; 3）评估这些传感器在猪模型中的体内分析性能。拟议的研究有可能导致植入式葡萄糖传感器，表现出减少生物污染和细菌感染，增强伤口愈合，并提高分析性能。具有这些特征的功能性葡萄糖传感器将影响数百万糖尿病患者，这些患者是连续葡萄糖监测设备的潜在候选人。公共卫生相关性本提案的目的是探索使用新型一氧化氮（NO）释放传感器膜来开发改进的皮下葡萄糖生物传感器，其在体内更可靠地发挥作用。拟议的研究有可能导致植入式葡萄糖传感器，表现出减少生物污染和细菌感染，增强伤口愈合，并提高分析性能。

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.