BIOSENSOR BIOCOMPATIBILITY

相当大的努力已经投入到开发居住治疗 依赖于闭环反馈控制的设备。在许多情况下，例如， 人工胰腺，需要一个生物传感器来持续监测 重要的生理参数尽管有几项研究 讨论了生物传感器，这些传感器在几周内成功地发挥了作用， 在体内，没有传感器能够可靠地长期存活 植入，主要是由于创伤的有害后果 愈合和异物反应。这个提议验证了 减轻了由伤口施加的分析物运输限制， 植入传感器的愈合过程将显著改善 生物传感器在体内的性能。我们将研究两个相关因素 伤口愈合限制了生物传感器对血液传播分析物的获取： (1)由传感器膜生物污染和 在植入传感器周围形成的致密纤维囊组织，以及 (2)由纤维组织的无血管性造成的灌注屏障 胶囊 在追求这一假设时，我们打算检查 以下关于体内生物传感器性能的设计修改：（1） 将纹理化的血管生成层结合到传感器包装中， 破坏纤维囊的形成并促进新血管形成; (2)将释放血管生成因子的可降解聚合物结合到 纹理化的血管生成层以进一步促进新血管形成;以及 (3)结合透析膜（可能具有水凝胶改性） 以使细胞沉积最小化， 蛋白质吸收RT动物模型将用于测试 这些修改对长期性能的影响 植入（即3-4个月）传感器。最后，这些修改将 在功能性葡萄糖生物传感器中进行检查， 生物材料就能发挥作用。

Considerable effort has gone into developing in-dwelling therapeutic devices that depend on closed loop feedback control. In many cases, e.g. the artificial pancreas, a biosensor is needed to continuously monitor crucial physiological parameters. Although several studies have discussed biosensors which successfully functioned for several weeks in vivo, no sensor appears capable of reliably surviving long-term implantation, primarily owing to the deleterious consequences of wound healing and the foreign body response. This proposal test the hypothesis that easing the analyte transport limitations imposed by the wound healing process on implanted sensors will significantly improve biosensor performance in vivo. We will examine two factors associated with wound healing that limit biosensor access for blood borne analytes: (1) diffusion barriers imposed by sensor membrane biofouling and the densely fibrous capsular tissue that forms around implanted sensors, and (2) perfusion barriers imposed by the avascularity of the fibrous capsule. In pursuing this hypothesis, we intend to examine the efficacy of the following design modifications on in vivo biosensor performance: (1) incorporate textured angiogenic layer into the sensor packaging to disrupt formation of the fibrous capsule and promote neovascularization; (2) incorporate degradable polymers that release angiogenic factors into the textured angiogenic layer to further promote neovascularization; and (3) incorporate dialysis membranes (possibly with hydrogel modification) into the active sensing surface to minimize cellular deposition and protein absorption. The rt animal model will be used to test the influence of these modifications on the performance of long term implanted (i.e. 3-4 months) sensors. Finally, these modifications will be examined in functioning glucose biosensors developed in parallel with the biomaterials work.