Biosensor Biocompatibility

临床意义几个小组已经报告了几周来血糖感受器的成功 在体内存活数月；然而，这些传感器似乎都不能在长期植入后可靠存活。 我们的全球假设是，抵抗生物污染的膜修饰和局部释放策略， 减轻炎症，减少周围伤口愈合组织的纤维性和无血管 最大限度地减少葡萄糖在传感器膜上传输的障碍。短期策略是检查 抗炎性类固醇和/或血管生成生长因子释放对葡萄糖转运的影响 传感器。虽然可能是有效的调解人，但我们进一步假设，这些方法是铁板一块的。 在他们的行动中是预防性的。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。这 因此，项目朝着这个方向迈出了第一步：确定关键炎症和 传感器植入部位的修复性巨噬细胞衍生细胞因子。 实验方法将微透析探针植入大鼠背部皮下将作为实时 方法：(1)表征葡萄糖通过已处理的植入传感器膜的传输 以抵抗生物污垢并增加植入探头周围组织的血管；以及(2)收集 细胞因子&植入探头周围的伤口愈合组织。收集的葡萄糖和 细胞因子将由商业化的酶联微量分析仪和定制的抗体阵列进行分析， 分别进行了分析。靶细胞因子为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、白介素1受体拮抗剂、白介素1β， IL-4、IL-6、IL-8和IL-10均为巨噬细胞来源的创面愈合和炎症介质。 细胞因子谱的时间成分、葡萄糖的获取和 在各种膜处理下的伤口愈合组织的组织学将被用于：(1)发展一种病因- 对传感器膜修饰对获取血液中分析物的影响的理解，以及(2)评估 巨噬细胞参与伤口愈合相关的植入传感器性能衰退。 ~ ‘ERFORMANCESITE(S)(组织，c@，州) 杜克大学 生物医学工程系 校园包厢90281 北卡罗来纳州达勒姆，27708-0281 关键人员。参见第11页的说明。根据需要使用第二页以下面的格式提供所需的信息 我的组织角色计划 威廉·M·赖切特杜克大学校长 调查员 布鲁斯·克里茨曼杜克大学研究员 范源杜克大学调查员 李毅文杜克大学访问学者 PHS 390(5/95版)PaoE 2 BB CC负责人调查员/项目总监(最后、第一、中间)：Reichert。威廉 在每张打印页和每张续页的顶部输入首席调查员/项目主任的姓名。(有关类型规格，请参阅 第6页上的说明。 研究补助金 目录 页码 FacePage...........................................................................................................1 描述，

Clinical significance Several groupshave reported glucose sensorsthat have hctionedsuccessf'ully for weeks to months in vivo;however, none of these sensors appear capable of reliablv 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-intlammatory 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 intlammatory 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-1P, 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 participationof macrophages in the wound healing-related decay of implanted sensor performance. ~ 'ERFORMANCESITE(S)(organization, c@, state) Duke University Department of BiomedicalEngineering Campus Box 90281 Durham, NC 27708-0281 KEY PERSONNEL. See instructionson Page 11. Usecontinuationpages as needed to providethe requiredinformation intheformat shmbelow me Orqanization Roleon Project WILLIAM M. REICHERT DUKE UNIVERSITY PRINCIPAL INVESTIGATOR BRUCE KLITZMAN DUKE UNIVERSITY INVESTIGATOR FAN YUAN DUKE UNIVERSITY INVESTIGATOR YIWEN LI DUKE UNIVERSITY VISITING SCHOLAR PHS 390 (Rev 5/95) Paoe 2 BB cc PrincipalInvestigator/ProgramDirector (Last, first, middle): Reichert. William Type the name of the principal investigator/program director at the top of each printed page and each continuation page. (For type specifications, see instructionson page6.) RESEARCH GRANT TABLE OF CONTENTS Page Numbers FacePage......................................................................................................... ............................................. 1 Description,