BIOSENSOR BIOCOMPATIBILITY

在开发住宅治疗方面已经做出了相当大的努力 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 关键的生理参数。尽管有几项研究已经 讨论了成功工作了几周的生物传感器 活体内，似乎没有传感器能够可靠地长期存活 植入，主要是由于伤口的有害后果 愈合和异物反应。这项提议检验了这一假设 缓解了伤口对分析物运输的限制 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。我们将研究相关的两个因素 伤口愈合限制了血液中分析物质的生物传感器访问： (1)传感器膜生物污染造成的扩散障碍和 在植入的传感器周围形成的致密纤维性包膜组织，以及 (2)纤维无血管所造成的灌流障碍 太空舱。 在追寻这一假设的过程中，我们打算检验 以下是对体内生物传感器性能的设计改进：(1) 将纹理血管生成层结合到传感器包装中以 破坏纤维包膜的形成，促进血管新生； (2)将释放血管生成因子的可降解聚合物 有纹理的新生血管层，以进一步促进新生血管形成；以及 (3)结合透析膜(可能带有水凝胶改性) 以最大限度地减少细胞沉积 蛋白质吸收。RT动物模型将用于测试 这些修改对长期业绩的影响 植入(即3-4个月)传感器。最后，这些修改将 在与开发的并行开发的功能性葡萄糖生物传感器中进行检测 生物材料起作用了。

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.