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Charakterisierung von Lipid-Oligolagen nach Zugabe von Hyaluronsäure und polymeren Ersatzstoffen zur Aufklärung möglicher Wirkmechanismen in der Viskosupplementation

Schwörer, Felicitas

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The probability of being affected by osteoarthritis during lifetime is about 20 % in Germany. The disease originates from a degenerative alteration of joints in which the lipid layers covering the cartilage and the cartilage itself are depleted, and the underlying bone is exposed. The treatment mainly includes pain-relieving therapies and physiotherapy for maintaining mobility. A long-term solution is only an artificial joint replacement (endoprosthesis) which, however, has to be inserted by surgery and must be replaced after about 10 to 15 years.

Since the 90s a new treatment called viscosupplementation exists. This non-surgical procedure promises to preserve one's own natural joint while at the same time recovering its functionality. It is based on studies on diseased joints, which showed that the volume of the synovial fluid increases while the concentration and the molecular weight (MW) of the contained hyaluronic acid (HS) decrease. Further investigations indicate that surfaceactive phospholipids (PLs) play an important role in joint lubrication in addition to the HS. Based on these findings, an intra-articular injection of hyaluronic acid (HS) or mixtures of HS and PL is used during viscosupplementation. However, the effectiveness of the method is discussed controversially.

The aim of this work was, therefore, to investigate the interactions of the main components in a joint by means of a simplified model system, and to examine the impact of HS and polymeric substitutes on PL layers covering the cartilage. Simultaneous in-situ neutron reflection (NR) and infrared (IR) measurements at the instrument BioRef at Helmholtz-Zentrum-Berlin (HZB) should provide insights into the internal structure and phase behavior of the lipid layers. The development of a custom-fit shear cell allows to simulate shear in joints and to gain information on the stability of the systems. Further systematic studies on the nature of interactions between PLs and HS or polymeric substitutes were carried out by means of ellipsometric measurements.

For the investigation of the interaction between PLs and polyelectrolyte (PE) or HS solutions, different parameters of the solutions were deliberately changed in the first experiments. In particular, the charge, the molecular weight and the concentration of the PEs or the HS, the concentration and type of added salts and the pH were varied. For this purpose, silicon substrates coated with lipid oligolayers and exposed to water were first characterized and served as an internal reference. After reaching equilibrium, the system was subjected to the above-mentioned changes, measured again and compared with the reference measurement.

For charged PEs, a strong increase in the lamellar layer thickness of the lipids was found at low concentrations, which decreased with increasing PE concentration. Uncharged polymers induced only low swelling, which increased slightly with increasing PE concentration. This indicated that the strong swelling behavior of the lipid layers is based on electrostatic interactions. It was assumed that the selective adsorption of the PEs on the lipid bilayers electrostatically charges the layers. Experiments on charge shielding byexposure to salt solutions and changes in pH as well as the modeling of NR data further confirmed this assumption.

The exact localization of the PE or HS molecules within the lipid layers should be facilitated by NR measurements. Modeling of the reflectivity curves for polyallylamine hydrochloride (PAH) with an average MW of 58 kDa showed an integration into the chain regions. By means of appropriate contrast variation in the systems utilizing deuterated lipids, a direct, model independent detection of the incorporation of PAH into the layer system was feasible so that possible sources of error during modeling could be excluded. Such incorporation suggests bridging of the lipid layers by HS and PEs, which can lead to the formation of a hydrogel-like structure possibly protecting the cartilage.

In line with the concept of the viscosupplementation, a stabilization of the lipid layers against shear could be determined upon addition of HS or the polymeric substitute PAH. However, the expected MW dependency could not be verified. HS showed a stronger stabilizing effect than the PAH, but only after markedly longer incubation times.

In the present work it was shown that HS and polymeric substitutes show a stabilizing effect on the lipid coating of the joints, which can possibly lead to a reconstitution of lowfriction joint movement. The idea of viscosupplementation appears to be promising, and by taking other components such as proteoglycans or cartilage coatings into consideration, an effective non-operative treatment of osteoarthritis should be possible in the future.

Item Type: Dissertation
Supervisor: Dahint, apl. Prof. Reiner
Date of thesis defense: 24 July 2017
Date Deposited: 22 Aug 2017 08:25
Date: 2017
Faculties / Institutes: Fakultät für Chemie und Geowissenschaften > Institute of Physical Chemistry
Subjects: 500 Natural sciences and mathematics
530 Physics
540 Chemistry and allied sciences
570 Life sciences
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