title: The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD) Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products.
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.
authors.affiliation: Laboratoire des Technologie des Composites et Polymères (LTC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Apicella
authors.affiliation: Food Process Engineering, Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Peggy
authors.initials: P
authors.lastname: Heunemann
authors.affiliation: Food and Soft Materials Science, Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Sreenath
authors.initials: S
authors.lastname: Bolisetty
authors.affiliation: Laboratoire des Technologie des Composites et Polymères (LTC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Marascio
authors.affiliation: Institut Straumann AG, 4052 Basel, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Gemperli Graf
authors.affiliation: Institut Straumann AG, 4052 Basel, Switzerland.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Garamszegi
authors.affiliation: Food and Soft Materials Science, Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Mezzenga
authors.affiliation: Food Process Engineering, Institute of Food, Nutrition and Health, ETH Zurich, 8092 Zurich, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Fischer
authors.affiliation: Laboratoire des Technologie des Composites et Polymères (LTC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Plummer
authors.affiliation: Laboratoire des Technologie des Composites et Polymères (LTC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Jan-Anders
authors.initials: JA
authors.lastname: Månson
mesh_terms: D001120:Arginine / Q000494:pharmacology*; D011232:Chemical Precipitation; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D000067493:Dynamic Light Scattering; D006863:Hydrogen-Ion Concentration; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D011487:Protein Conformation; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013312:Stress, Physiological / Q000187:drug effects*; D013696:Temperature
chemical_list: D003746:Dental Enamel Proteins; D012996:Solutions; C109069:enamel matrix proteins; D001120:Arginine