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Protection of Cartilage in Natural Joints: Investigation of the Impact of Hyaluronic Acid and Polymeric Substitutes on the Structure and Stability of Surface-Bound Lipid Layers

自然关节软骨的保护：研究透明质酸和聚合物替代品对表面结合脂质层的结构和稳定性的影响

基本信息

批准号：
270667246
负责人：
Professor Dr. Reiner Dahint
金额：
--
依托单位：
Forschungsgruppe für Angewandte Physikalische Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/270667246?language=en
关键词：
Protection Cartilage Natural Joints Investigation

项目摘要

Osteoarthritis is the most common joint disease in the western world. It typically starts with a degeneration of the cartilage, leading to increased friction in the joint, stiffness, and inflammation. A much discussed treatment is the so-called viscosupplementation which is based on the intra-articular injection of hyaluronic acid (HA). HA is a negatively charged polysaccharide that forms an essential component of the joint fluid. At physiological conditions HA supposedly bears friction-reducing properties. It is further believed that HA, adsorbed to cartilage, forms a protective layer against wear under operational demands of the joint. The underlying mechanisms of viscosupplementation, however, are not known in detail and its effectiveness is subject of current medical research. A special focus lies on the dependence of a possible successful treatment on molecular weight and concentration of HA as well as on the exclusion of placebo effects.The aim of the research project is to systematically investigate the effects of HA on the layer formation in joints using a model system. Since the articular cartilage is covered by a lipid layer, which in turn is in contact with the joint fluid, the focus of the studies will be on the influence of HA on the structure and stability of surface-bound lipid films. In fact, a stabilizing effect of HA on lipid layers was observed in initial experiments. On basis of these results we will develop a detailed understanding of the mechanisms, which determine structure formation and promote stability. An important aspect will be to investigate which specific properties of HA contribute to the stability of the terminal lipid layers and whether polymeric substitutes for HA are as effective or even more appropriate for achieving the desired functionality. Of particular interest will be the question on the influence of molecular weight, concentration and charge of the polymer used, ionic strength and pH of the embedding aqueous solution as well as the response of the interfacial layers formed to mechanical load.Main characterization technique is a combination of in situ neutron reflectometry and infrared spectroscopy, which provides detailed information on both the internal structure and composition of the layers as well as on the molecular conformation. For this purpose a novel neutron reflectometer with integrated infrared analysis, which was built by us, is available at the Helmholtz-Zentrum Berlin. Pressure and shear cells have been developed for the experimental investigation of applied mechanical stresses in the model joint system, and will also be used in the stability tests. Additional structural investigations of the respective solid/liquid interfaces will be conducted with a suitable X-ray reflectometer. Above studies will be complemented by other surface analytical in situ techniques such as ellipsometry, quartz-crystal-microbalance measurements and atomic force microscopy in liquid phase.

骨关节炎是西方世界最常见的关节疾病。它通常始于软骨的退化，导致关节摩擦力增加，僵硬和炎症。一种讨论较多的治疗方法是所谓的粘弹性补充，其基于透明质酸（HA）的关节内注射。HA是一种带负电荷的多糖，形成关节液的基本成分。在生理条件下，HA被认为具有减少摩擦的特性。进一步认为，吸附到软骨上的HA在关节的操作需求下形成防止磨损的保护层。然而，粘弹性补充的潜在机制尚不清楚，其有效性是当前医学研究的主题。一个特别的重点在于一个可能的成功治疗的依赖性的分子量和浓度的HA以及排除安慰剂effects.The目的的研究项目是系统地调查HA对层形成关节使用模型系统。由于关节软骨被脂质层覆盖，而脂质层又与关节液接触，因此研究的重点将是HA对表面结合脂质膜的结构和稳定性的影响。事实上，在最初的实验中观察到HA对脂质层的稳定作用。在这些结果的基础上，我们将详细了解决定结构形成和促进稳定性的机制。一个重要的方面将是研究HA的哪些特定性质有助于末端脂质层的稳定性，以及HA的聚合物替代物是否同样有效或甚至更适合于实现所需的功能。特别令人感兴趣的是关于所用聚合物的分子量、浓度和电荷、包埋水溶液的离子强度和pH以及所形成的界面层对机械负荷的响应的影响的问题。主要表征技术是原位中子反射计和红外光谱的组合，其提供了关于层的内部结构和组成以及分子构象的详细信息。为此，我们在柏林的亥姆霍兹-Zentrum中心研制了一种新型的带有红外分析功能的中子反射计。压力和剪切单元已开发用于模型接缝系统中施加的机械应力的实验研究，并且也将用于稳定性测试。将使用合适的X射线反射计对相应的固/液界面进行额外的结构调查。上述研究将补充其他表面分析原位技术，如椭圆偏振法，石英晶体微天平测量和原子力显微镜在液相中。