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

骨关节炎是西方世界最常见的关节疾病。它通常以软骨退化开始，导致关节摩擦增加，僵硬和炎症。一种被广泛讨论的治疗方法是所谓的粘胶补充，它是基于关节内注射透明质酸（HA）。透明质酸是一种带负电荷的多糖，是关节液的重要组成部分。在生理条件下，透明质酸被认为具有减少摩擦的特性。进一步认为，在关节的操作要求下，透明质酸被吸附在软骨上，形成防止磨损的保护层。然而，粘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。一个特别的焦点在于可能成功的治疗依赖于HA的分子量和浓度以及对安慰剂效应的排除。该研究项目的目的是利用模型系统系统地研究HA对节理层形成的影响。由于关节软骨被脂质层覆盖，而脂质层又与关节液接触，因此研究的重点将放在HA对表面结合脂质膜结构和稳定性的影响上。事实上，在最初的实验中观察到透明质酸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透明质酸的哪些特定性质有助于末端脂质层的稳定性，以及透明质酸的聚合物替代品是否同样有效，甚至更适合实现所需的功能。特别令人感兴趣的问题是所使用的聚合物的分子量、浓度和电荷、包埋水溶液的离子强度和pH值以及形成的界面层对机械负载的响应的影响。主要的表征技术是原位中子反射法和红外光谱法的结合，它提供了层的内部结构和组成以及分子构象的详细信息。为此，我们在柏林亥姆霍兹中心研制了一种新型的中子反射计，具有综合红外分析功能。压力和剪切单元已被开发用于模型节点系统的应用机械应力的实验研究，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体/液体界面进行额外的结构研究。上述研究将辅以其他表面原位分析技术，如椭圆偏振、石英晶体微天平测量和液相原子力显微镜。

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.