Role of diabetes and nitric oxide release duration on analytical performance of in vivo glucose biosensors

项目摘要 本项目的目的是研究一氧化氮（NO）释放的分析性能的好处 在糖尿病猪模型中作为NO释放持续时间传感器的函数的Percent植入葡萄糖传感器 膜孔隙率和糖尿病状态（即，胰岛素与非胰岛素依赖性）。持续葡萄糖监测 (CGM)具有上级可用性的设备（即，立即使用和延长期限）将大大增加 糖尿病患者成功控制疾病的能力。在上一个融资周期，我们 在非胰岛素依赖性糖尿病猪模型中证实，NO释放传感器膜既减少了 FBR和促进提高分析传感器性能长达28天-评估的最长持续时间。然而，在这方面， CGM器械预期用于胰岛素依赖型个体，较长的植入期将改善器械 效用/价值。胰岛素依赖和非胰岛素依赖受试者的FBR和体内传感器性能的方差为 目前尚不清楚，但由于伤口愈合机制受损更严重，可能具有显著意义。我们假设 FBR和传感器性能的改进，我们已经报道了释放NO 28天的传感器膜 将延长到至少两个月，通过使用多孔传感器膜，释放60天以上，被动 促进传感器附近的健康血管再生。通过我们的工作，我们将研究 NO释放和孔隙率对组织生物相容性和传感器性能的影响是糖尿病的函数。在这 在这方面，我们将产生关于糖尿病如何影响组织整合和体内传感器的新知识。 性能

PROJECT SUMMARY The objective of this project is to study the analytical performance benefits of nitric oxide (NO)-releasing percutaneously implanted glucose sensors in a diabetic swine model as a function of NO-release duration sensor membrane porosity, and diabetes state (i.e., insulin versus non-insulin dependent). Continuous glucose monitoring (CGM) devices with superior usability (i.e., for immediate use and extended duration) would greatly increase the ability of those afflicted with diabetes to successfully manage their disease. In the prior funding period, we demonstrated in a non-insulin dependent diabetic swine model that NO-releasing sensor membranes both lessen the FBR and facilitate improved analytical sensor performance up to 28 days—the longest duration evaluated. However, CGM devices are intended for insulin-dependent individuals and longer implantation periods would improve device utility/value. The variance in FBR and in vivo sensor performance for insulin- and non-insulin-dependent subjects is currently unknown but likely significant due to more impaired wound healing mechanisms. We hypothesize that the improvements in FBR and sensor performance that we have reported sensor membranes that release NO for 28 days will be extended to at least two months by using porous sensor membranes that release for 60+ days and passively promote healthy re-vascularization in the proximity of the sensor. Through our work, we will study the influence of both NO release and porosity on tissue biocompatibility and sensor performance as a function of diabetes. In this respect, we will generate new knowledge on how diabetes influences the tissue integration and in vivo sensor performance.