The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD) Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products |
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Authors: | Alessandra Apicella Peggy Heunemann Sreenath Bolisetty Matteo Marascio Anja Gemperli Graf Laszlo Garamszegi Raffaele Mezzenga Peter Fischer Christopher J Plummer Jan-Anders M?nson |
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Institution: | 1. Laboratoire des Technologie des Composites et Polymères (LTC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.; 2. Food Process Engineering, Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland.; 3. Food and Soft Materials Science, Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland.; 4. Institut Straumann AG, 4052 Basel, Switzerland.; Institute for Bioengineering of Catalonia, SPAIN, |
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Abstract: | In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD), which is the active component, is mixed with a propylene glycol alginate (PGA) gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as Emdogain™ through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications. |
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