Quantitative Biocompatibility of Implanted Materials

植入材料的定量生物相容性

• 批准号: 6940975
• 负责人: JULIE A STENKEN
• 金额: $ 5万
• 依托单位: RENSSELAER POLYTECHNIC INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-11 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6940975
• 关键词: Raman spectrometry; adsorption; biochemistry; biological fluid transport; biomaterial compatibility; biomaterial interface interaction; biotechnology; cytokine; eicosanoids; elastases; enzyme linked immunosorbent assay; high performance liquid chromatography; laboratory rat; macrophage; microdialysis; nitric oxide; tissue /cell culture

DESCRIPTION (provided by applicant): Clinical Significance. The time course and in vivo concentrations of macrophage-derived inflammatory chemical mediators associated with modulating the foreign body response to implanted materials at the host interface are not fully known. The lack of this needed information for a macrophage-centered hypothesis of biocompatibility is a primary obstacle to developing a quantitative theory of biocompatibility. Our primary hypothesis is that biocompatibility can only become more quantitative with the ability to measure the real time concentrations of chemical interactions/mediators at the biomaterial/tissue interface. Only then can these concentrations be compared to material chemistry, protein adsorption, and the efficacy of bioengineering approaches to wound healing at biomaterial implant sites. Macrophages are important cells associated with the inflammatory response to implanted materials. To achieve our objective of measuring macrophage-derived chemical mediators, the non-selective nature of microdialysis sampling will be used as a means to collect a fraction of the extracellular fluid space surrounding the biomaterial implant. Knowledge of the concentration and temporal profiles of these mediators will provide a more quantitative approach to biocompatibility. This knowledge can be applied to bioengineering approaches for solving problems in biomaterials biocompatibility Experimental Approach. Cultured macrophages will be used to (1) validate and ensure sensitivity of the analytical techniques; and (2) develop an understanding of the potentially complex microdialysis calibration issues that may arise during in vivo studies. For in vivo studies, two microdialysis probes will be implanted into the dorsal subcutis of male Sprague-Dawley rats. One probe will serve as a control and the other probe will either be placed in the presence of the targeted biomaterial (polyurethanes, Nation, PVC, etc.). Zymosan (a product that creates an inflammatory response) will be used as a positive control. The collected dialysate will be analyzed by using specific analytical techniques directed towards the analysis of nitric oxide, oxidative burst, eicosanoids (LTB4 and PGE2), cytokines (TNF-oc, IL-4, and IL-6) and localized elastase activity. Additional animal experiments will explore how localized blood flow is altered during the progression of the foreign body response. The completion of these first time in vivo studies focused on gaining quantitative chemical mediator concentration at the biomaterials implant site will help guide future research focused on modulating macrophage cells at the biomaterial implant site.

描述(申请人提供)：临床意义。巨噬细胞衍生的炎症化学介质在宿主界面调节异物对植入材料的反应的时间进程和体内浓度尚不完全清楚。缺乏以巨噬细胞为中心的生物相容性假说所需的这些信息是发展生物相容性定量理论的主要障碍。我们的主要假设是，只有通过测量生物材料/组织界面上化学相互作用/介体的实时浓度，生物相容性才能变得更加定量。只有到那时，这些浓度才能与材料化学、蛋白质吸附以及生物工程方法在生物材料植入部位伤口愈合方面的有效性进行比较。巨噬细胞是与植入材料的炎症反应相关的重要细胞。为了实现我们测量巨噬细胞衍生的化学介质的目标，微透析采样的非选择性性质将被用作收集生物材料植入物周围的一小部分细胞外液空间的手段。了解这些介体的浓度和时间分布将提供一种更定量的生物相容性方法。这些知识可以应用于解决生物材料生物相容性问题的生物工程方法。 实验方法。培养的巨噬细胞将用于(1)验证和确保分析技术的灵敏度；以及(2)了解体内研究期间可能出现的潜在复杂的微透析校准问题。为了进行活体研究，两个微透析探头将被植入雄性SD大鼠的背侧皮下。一个探头将作为对照，另一个探头将放置在目标生物材料(聚氨酯、Nation、PVC等)存在的情况下。酵母多糖(一种产生炎症反应的产品)将被用作阳性对照。收集的透析液将通过使用专门的分析技术进行分析，以分析一氧化氮、氧化爆发、二十烷类化合物(LTB4和PGE2)、细胞因子(TNF-oc、IL-4和IL-6)和局部弹性蛋白酶活性。其他动物实验将探索异物反应过程中局部血流是如何改变的。这些首次体内研究的完成侧重于获得生物材料植入部位的定量化学介体浓度，这将有助于指导未来专注于调节生物材料植入部位巨噬细胞的研究。