Biosensor Biocompatibility

描述(申请人提供：临床意义几个小组报告了葡萄糖传感器在体内成功工作了几周到几个月；然而，这些传感器似乎都不能在长期植入后可靠存活。我们的总体假设是，膜修饰和局部释放策略可以抵抗生物污染，减轻炎症，减少周围伤口愈合组织的纤维性和无血管，将最大限度地减少葡萄糖通过传感器膜运输的障碍。短期策略是检查抗炎类固醇和/或血管生成生长因子释放对葡萄糖转运到传感器的影响。虽然这些方法可能是有效的调解人，但我们进一步假设，这些方法在其行动中是铁板一块的和预防性的。从长远来看，伤口愈合干预的最高水平将是直接操纵植入传感器周围伤口愈合组织中的巨噬细胞。目前，提出以巨噬细胞为中心的策略所需的信息库还不存在。因此，该项目朝着这个方向迈出了第一步：确定传感器植入部位关键的炎症和修复性巨噬细胞衍生细胞因子的时间分布。实验方法植入大鼠背部皮下的微透析探针将作为一种实时方法用于(1)表征植入的传感器膜之间的葡萄糖运输，这些传感器膜经过抗生物污染处理并增加植入探针周围组织的血管；以及(2)收集植入探针周围的伤口愈合组织中的细胞因子。收集的葡萄糖和细胞因子将分别由商业化的酶联微量分析仪和定制的抗体阵列进行分析。靶细胞因子包括碱性成纤维细胞生长因子、血小板衍生生长因子、肿瘤坏死因子-α、转化生长因子-β、IL-1受体拮抗剂和IL-1β、IL-4、IL-6、IL-8和IL-10，它们都是巨噬细胞来源的创面愈合和炎症介质。在不同的膜处理下，细胞因子图谱的时间成分、葡萄糖的获取和伤口愈合组织的组织学之间的相关性将被用来：(1)建立传感器膜修改对获得血载分析物的因果关系的理解，以及(2)评估巨噬细胞在伤口愈合相关的植入传感器性能衰退中的参与。

DESCRIPTION (provided by applicant: Clinical significance Several groups have reported glucose sensors that have functioned successfully for weeks to months in vivo; however, none of these sensors appear capable of reliable surviving long-term implantation. Our global hypothesis is that membrane modifications and local release strategies that resist biofouling, attenuate inflammation, and reduce the fibrosity and avascularity of the surrounding wound healing tissue will minimize impediments to glucose transport across the sensor membrane. The short term strategy is to examine the effect of anti-inflammatory steroids and/or angiogenic growth factor release on glucose transport to the sensor. Although likely to be effective mediators, we further hypothesize that these approaches are monolithic and prophylactic in their action. In the long term, the highest level of wound healing intervention would be to directly manipulate the macrophages residing in the wound healing tissue surrounding implanted sensor. Currently, the information base necessary to propose a macrophage-centered strategy does not exist. This project therefore takes the first step in this direction: determining the temporal profile of key inflammatory and reparative macrophage-derived cytokines in the sensor implant site. Experimental approach Microdialysis probes implanted in dorsal rat subcutis will be used as a real time method to (1) characterize the transport of glucose across implanted sensor membranes that have been treated to resist biofouling and increase vascularity of the tissue surrounding the implanted probe; and (2) collect cytokines &om the wound healing tissue surrounding the implanted probes. The collected glucose and cytokines will be analyzed by a commercial enzyme-linked microanalyzer and a custom-made antibody array, respectively. The target cytokines are basic-FGF, PDGF, TNF-a, TGF-P, IL-1 receptor antagonist, and IL-1 P, IL-4, IL-6, IL-8 and IL-10, all of which are macrophage-derived mediators of wound healing and inflammation. Correlation between the temporal composition of the cytokine profile, the acquisition of glucose, and the histology of the wound healing tissue under various membrane treatments will be used to: (1) develop a cause- and-effect understandings of sensor membrane modifications on access to blood borne analytes, and (2) assess the participation of macrophages in the wound healing-related decay of implanted sensor performance