Biosensor Biocompatibility

临床意义几个研究小组已经报道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可靠地在长期植入中存活。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化和无血管性，从而最大限度地减少葡萄糖在传感器膜上运输的障碍。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。虽然可能是有效的中介，我们进一步假设，这些方法是单一的和预防性的行动。从长远来看，最高水平的伤口愈合干预将是直接操纵居住在植入传感器周围的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并不存在。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炎症和修复性巨噬细胞来源的细胞因子的时间分布。植入大鼠背部皮下的微透析探针将被用作一种实时方法来(1)表征葡萄糖在植入的传感器膜上的运输，这些传感器膜已被处理以抵抗生物污垢并增加植入探针周围组织的血管性；(2)从植入探针周围的伤口愈合组织中收集细胞因子。收集的葡萄糖和细胞因子将分别通过商用酶联微分析仪和定制抗体阵列进行分析。靶细胞因子为碱性fgf、PDGF、TNF-a、TGF-P、IL-1受体拮抗剂以及IL-1 P、IL-4、IL-6、IL-8和IL-10，它们都是巨噬细胞来源的伤口愈合和炎症介质。细胞因子谱的时间组成、葡萄糖的获取和不同膜处理下伤口愈合组织的组织学之间的相关性将被用于：(1)对获取血源性分析物的传感器膜修饰进行因果理解；(2)评估巨噬细胞在植入传感器性能的伤口愈合相关衰减中的参与

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