Thermal treatment at 500 degrees C significantly reduces the reaction to irregular tricalcium phosphate granules as foreign bodies: An in vivo study

Evaporation of phosphate species during thermal treatment (>400 degrees C) of calcium phosphates leads to the formation of an alkaline layer on their surface. The aim of this study was to evaluate the hypothesis that the biological response of thermally treated calcium phosphates is modified by the presence of such an alkaline layer on their surface. For this purpose, 0.125-0.180 mm alpha- and beta-tricalcium phosphate (TCP) granules were obtained by crushing and size classification, with some being subjected to thermal treatment at 500 degrees C. The four types of granules (alpha-TCP, beta-TCP, alpha-TCP-500 degrees C, and beta-TCP-500 degrees C) were implanted subcutaneously and orthotopically in rats. Sham operations served as control. Subcutaneously, alpha-TCP and beta-TCP induced significantly more multinucleated giant cells (MNGCs) than calcined granules. Most of the induced MNGCs were TRAP-negative, CD-68 positive and cathepsin K-negative, reflecting a typical indication of a reaction with a foreign body. The vessel density was significantly higher in the alpha-TCP and beta-TCP groups than it was in the alpha-TCP-500 degrees C and beta-TCP-500 degrees C groups. In the femur model, beta-TCP-500 degrees C induced significantly more new bone formation than that induced by beta-TCP. The granule size was also significantly larger in the beta-TCP-500 degrees C group, making it more resistant to degradation than beta-TCP. The MNGC density was higher in the alpha-TCP and beta-TCP groups than in the alpha-TCP-500 degrees C and beta-TCP-500 degrees C groups, including cathepsin-positive, CD-68 positive, TRAP-positive and TRAP-negative MNGCs. In conclusion, this study confirms that the biological response of calcium phosphates was affected by the presence of an alkaline layer on their surface. Thermally-treated alpha-TCP and beta-TCP granules produced significantly fewer MNGCs and were significantly less degraded than non-thermally-treated alpha-TCP and beta-TCP granules. Thermally treating alpha-TCP and beta-TCP granules shifts the reaction from a foreign body reaction towards a physiological reaction by downregulating the number of induced MNGCs and enhancing degradation resistance. Statement of significance Changes of biomaterials surface (polymers, ceramics, metals) is a key to modulate the biomaterial induced inflammatory pattern and thereby have a direct influence on the regenerative capacity. This is the reason why the effect of thermal treatment of alpha- and beta-tricalcium phosphate granules at 500 degrees C was studied. To the best of our knowledge, this is the first article focusing on modulating the cellular reaction by thermal treatment of alpha- and beta-tricalcium phosphate granules. We believe that the manuscript will provide important insights understanding the direct influence of the biomaterials physicochemical characteristics on the cellular reaction and the regenerative pattern in vivo. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.