Cell Membrane Simulators in Biocompatibility Testing

描述(由申请人提供)： 细胞损伤始于细胞防御的第一级，即细胞膜。从牙科修复剂中浸出的化学物质会通过作用于膜表面而损害周围的细胞组织。这项研究建立了一种生物相容性测试中缺失的新方法，以测量细胞结构、组织和功能所必需的膜的破坏。这一目标将使用由磷脂小泡产生的仿生细胞膜来实现。这些模拟器或“生物模拟器”将具有特定的磷脂组成和酶活性。设计和标准化的BioSIMs将面临系统系列牙科单体的挑战，以及通过量子力学-定量结构活性关系(QMSAR)在膜分子水平上发现损伤的主要原因。设计BioSims的技术可从申请者的国际联网实验室获得。在应用这项技术作为生物相容性测试系统时，BioSims的具体目标将达到以下目标：1)建立用于生物测试目的的每种生物模拟物类型的重复性；2)通过研究BioSims的热力学来提高对细胞膜的了解；3)通过确定它们对BioSIMs通透性的影响来提高对牙科单体细胞膜通透性的了解；4)使用将被开发和标准化为乙酰胆碱酯酶和胆固醇酯酶的仿生细胞膜模拟器的囊泡来建立生物材料对膜结合酶的影响；以及5)使用QMSARs来预测新型生物材料的性质以从其化学结构中去除膜和酶的破坏性基团。由于在汞齐聚合物树脂替代品的配方中使用了越来越多的毒性未指明的化学品，因此该测试系统是必要的。现有的细胞培养和动物试验忽略了有关生物材料在膜分子间连接中造成干扰的能力的信息。这个新系统的一个优点是不需要实验动物。Biosim/QMSAR方法将提供特定的热力学和原因结构描述符，有助于解释生物材料造成膜损伤的分子基础。这将使预测未经测试的化合物的破坏性性能成为可能，并确保设计新的无毒牙膜材料。

DESCRIPTION (provided by applicant): Cell injury begins at the first level of cell defense, the membrane. Chemicals leaching from dental restoratives can damage surrounding cellular tissue by acting at membrane surfaces. This research establishes a new method missing in biocompatibility tests to measure damage by disruption of membranes essential for cell structure, organization and function. The objective will be accomplished using biomimetic cell membranes created from phospholipid vesicles. These simulators or "BioSims" will have specified phospholipid composition and enzymatic activities. Designed and standardized BioSims will be challenged with dental monomers in systematic series and the primary causes of damage at the membrane molecular level discovered through quantum mechanical - quantitative structure activity relationships (QMSAR). The technology for designing BioSims is available from the applicant internationally networked laboratories. In applying this technology as a biocompatibility test system, the specific aims for the BioSims will accomplish the following: 1) establish reproducibility of each BioSim type produced for bioassay purposes; 2) improve knowledge of cell membranes through the study of the thermodynamics of BioSims; 3) improve knowledge of dental monomer cell membrane permeability by determining their effect on the permeability of BioSims; 4) establish effects of biomaterials on membrane bound enzymes that are critical in biological homeostasis using vesicles which will be developed and standardized as Biomimetic Cell Membrane Simulators of Acetylcholinesterase and Cholesterol Esterase and 5) employ QMSARs to predict the properties of new biomaterial to remove membrane and enzymatic destructive moieties from their chemical structure. This test system is necessary due to the increasing use of toxicologically unspecified chemicals in the formulation of polymer resin substitutes for mercury amalgam. Cell culture and animal tests available omit information on the ability of biomaterials to create disturbances in membrane intermolecular linkages. An advantage of this new system is that no experimental animals will be required. The BioSim/QMSAR approach will provide specific thermodynamics and causative structure descriptors that will help explain the molecular basis of membrane injury from biomaterials. This will enable the prediction of destructive properties of untested compounds and ensure the design of new non-toxic membrane dental materials.