Thermal treatment at 500°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°C) of calcium phosphates leads to the formation of an alkaline layer on their surface. The aim of this study was to evaluate the hypothe- sis 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 α- and β-tricalcium phosphate (TCP) granules were obtained by crushing and size classification, with some being subjected to thermal treatment at 500°C. The four types of granules (α-TCP, β-TCP, α-TCP-500°C, and β-TCP-500°C) were implanted subcutaneously and orthotopically in rats. Sham operations served as control. Subcutaneously, α-TCP and β-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 signifi- cantly higher in the α-TCP and β-TCP groups than it was in the α-TCP-500°C and β-TCP-500°C groups. In the femur model, β-TCP-500°C induced significantly more new bone formation than that induced by β-TCP. The granule size was also significantly larger in the β-TCP-500°C group, making it more resistant to degradation than β-TCP. The MNGC density was higher in the α-TCP and β-TCP groups than in the α-TCP-500°C and β-TCP-500°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 α-TCP and β-TCP granules produced significantly fewer MNGCs and were significantly less degraded than non-thermally-treated α-TCP and β-TCP granules. Thermally treating α-TCP and β-TCP granules shifts the reaction from a foreign body re- action towards a physiological reaction by downregulating the number of induced MNGCs and enhancing degradation resistance. Changes of biomaterials surface (polymers, ceramics, metals) is a key to modulate the bioma- terial induced inflammatory pattern and thereby have a direct influence on the regenerative capacity. This is the reason why the effect of thermal treatment of α- and β-tricalcium phos- phate granules at 500°C was studied. To the best of our knowledge, this is the first article fo- cusing on modulating the cellular reaction by thermal treatment o