Quantitative Biocompatibility of Implanted Materials

描述（由申请人提供）：临床意义。与调节宿主界面处植入材料的异物反应相关的巨噬细胞源性炎症化学介质的时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，生物相容性只有在能够测量生物材料/组织界面处化学相互作用/介质的真实的时间浓度时才能变得更加定量。只有这样，这些浓度才能与材料化学，蛋白质吸附和生物工程方法在生物材料植入部位伤口愈合的功效进行比较。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将被用作收集生物材料植入物周围的细胞外液空间的一部分的手段。了解这些介质的浓度和时间分布将为生物相容性提供更定量的方法。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;和（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。对于体内研究，将两个微透析探针植入雄性Sprague-Dawley大鼠的背侧皮下组织中。一个探针将作为对照，另一个探针将放置在存在目标生物材料（聚氨酯、Nation、PVC等）的情况下。酵母聚糖（一种产生炎症反应的产品）将用作阳性对照。将使用特定的分析技术对收集的透析液进行分析，这些分析技术旨在分析一氧化氮、氧化爆发、类花生酸（LTB 4和PGE 2）、细胞因子（TNF-α、IL-4和IL-6）和局部弹性蛋白酶活性。另外的动物实验将探索在异物反应的进展过程中局部血流是如何改变的。完成这些首次体内研究，重点是在生物材料植入部位获得定量化学介质浓度，将有助于指导未来的研究，重点是在生物材料植入部位调节巨噬细胞。

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.