Biosensor Biocompatibility

描述（由申请人提供）：今天，超过1800万美国人患有胰岛素依赖型II型糖尿病。据估计，一半的II型糖尿病患者不能或不愿意使用标准的手指针刺方案来适当地调节自己的葡萄糖。这些人中的许多人将极大地受益于留置的闭环胰岛素递送装置，例如采用传感器来连续监测血液或间质液中的葡萄糖水平的人工胰腺。尽管有几个研究小组已经报道了在体内成功运行数周至数月的生物传感器，但似乎没有葡萄糖传感器能够可靠地和可预测地长期植入。因此，所有FDA批准的葡萄糖探头均被视为仅适用于急性应用。假设：我们的总体假设是，葡萄糖传感器长期留置应用的最后一个障碍是伤口愈合介导的传感器失效。我们通过设计和表征膜修饰和局部释放策略来解决这一假设，所述膜修饰和局部释放策略（1）抵抗生物污垢，（2）减轻炎症，（3）减少纤维化和（4）促进周围伤口愈合组织的血管化，将最大限度地减少葡萄糖穿过传感器膜的运输的障碍。这种竞争性更新分为翻译和实验目标。转化目标是将地塞米松、VEGF和上一个融资周期中开发的纹理化策略应用于FDA批准的Medtronic Diabetes SOF-SENSORTM葡萄糖探头。这将包括在完整组织中的植入，以及首次使用背侧经皮窗室大鼠模型直接观察紧邻皮下植入传感器附近的组织结构的演变。实验目标还研究了仿生策略，该策略采用接种的脂肪源性干细胞（ASC）来介导炎症并促进植入传感器周围组织中的血管形成。在每种情况下，来自窗口室图像和实况传感器响应的实验结果将使用具有血液传播的葡萄糖的传感器表面的灌注的传输建模来基准化。将使用更精确的模型来预测微血管密度、纤维包裹和生物污垢对观察到的传感器响应的预期影响。公共卫生相关性：该项目解决了葡萄糖探头长期留置应用的最后一个障碍-探头无法可靠和可预测地长期植入。

DESCRIPTION (provided by applicant): More than 18 million Americans suffer today from insulin-dependent, type II diabetes. It is estimated that half of type II diabetics are unable or unwilling to properly gluco-regulate themselves using the standard finger stick regimen. Many of these people would benefit greatly from an indwelling, closed loop insulin delivery device, e.g. the artificial pancreas that employs a sensor to continuously monitor glucose levels in either blood or interstitial fluid. Although several groups have reported biosensors that have successfully functioned for weeks to months in vivo, no glucose sensor appears capable of reliably and predictably surviving long-term implantation. Consequently, all FDA-approved glucose sensors are deemed suitable for acute applications only. Hypothesis: Our global hypothesis is that the last remaining barrier to the application long-term indwelling of glucose sensors is surviving wound-healing mediated sensor failure. We address this hypothesis by devising and characterizing membrane modifications and local release strategies that (1) resist biofouling, (2) attenuate inflammation, (3) reduce the fibrosity and (4) promote vascularity of the surrounding wound healing tissue will minimize impediments to glucose transport across the sensor membrane. This competitive renewal is divided into translational and experimental objectives. The translational objective is the application of dexamethasone, VEGF and texturing strategies developed in the previous funding cycle to FDA-approved Medtronic Diabetes SOF-SENSORTM glucose sensors. This will include implantation in intact tissue, as well as the first-time use of a dorsal transcutaneous window chamber rat model to directly observe the evolution of tissue architecture in the vicinity immediately adjacent to a subcutaneously implanted sensor. The experimental objectives also examine biomimetic strategies that employ seeded adipose-derived stems cells (ASC) for mediating inflammation and promoting vessel formation in the tissue surrounding implanted sensors. In each case, the experimental results from the window chamber images and the live senor responses will be benchmarked using transport modeling of perfusion of the sensor surface with blood borne glucose. A more precise model will be used to predict the anticipated affects of microvessel density, fibrous encapsulation, and biofouling on the observed sensor response. PUBLIC HEALTH RELEVANCE: This project addresses the last remaining barrier to the application long-term indwelling of glucose sensors - the inability of sensors to reliably and predictably survive long- term implantation.