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

项目概要 该项目的目标是研究一氧化氮 (NO) 释放的分析性能优势 在糖尿病猪模型中经皮植入葡萄糖传感器作为 NO 释放持续时间传感器的函数 膜孔隙率和糖尿病状态（即胰岛素依赖型与非胰岛素依赖型）。连续血糖监测 具有卓越可用性（即立即使用和延长持续时间）的（CGM）设备将大大提高 糖尿病患者成功控制疾病的能力。在之前的资助期间，我们 在非胰岛素依赖型糖尿病猪模型中证明，释放 NO 的传感器膜可以减轻 FBR 有助于提高分析传感器性能长达 28 天——评估的最长持续时间。然而， CGM 设备适用于胰岛素依赖者，较长的植入时间将改善设备的性能 效用/价值。胰岛素依赖型和非胰岛素依赖型受试者的 FBR 和体内传感器性能差异为 目前尚不清楚，但由于伤口愈合机制受损，可能很重要。我们假设 FBR 和传感器性能的改进，我们已报告传感器膜可释放 NO 28 天 通过使用可释放 60 天且被动的多孔传感器膜，将延长至至少两个月 促进传感器附近的健康血运重建。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，与糖尿病有关。在这个 尊重，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.