The effect of grain size on the biocompatibility, cell–materials interface, and mechanical properties of microwave-sintered bioceramics Djordje Veljovic ´, 1 Miodrag C ˇ olic ´, 2 Vesna Kojic ´, 3 Gordana Bogdanovic ´, 3 Zvezdana Kojic ´, 4 Andrijana Banjac, 5 Eriks Palcevskis, 6 Rada Petrovic ´, 1 Djordje Janac ´ kovic ´ 1 1 Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, Belgrade 11120, Serbia 2 Institute for Medical Research, Military Medical Academy, Crnotravska 17, Belgrade 11002, Serbia 3 Institute of Oncology Sremska Kamenica, Institutski Put 4, Sremska Kamenica 21204, Serbia 4 Institute of Medical Physiology, School of Medicine, University of Belgrade, Dr Subotica 8, Belgrade 11000, Serbia 5 Faculty of Veterinary Medicine, University of Belgrade, Bulevar oslobodjenja 18, Belgrade 11000, Serbia 6 Institute of Inorganic Chemistry, Riga Technical University, Miera 34, Salaspils, Riga LV-2169, Latvia Received 4 January 2012; revised 20 March 2012; accepted 23 April 2012 Published online 00 Month 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.34225 Abstract: The effect of decreasing the grain size on the bio- compatibility, cell–material interface, and mechanical proper- ties of microwave-sintered monophase hydroxyapatite bioceramics was investigated in this study. A nanosized stoi- chiometric hydroxyapatite powder was isostatically pressed at high pressure and sintered in a microwave furnace in order to obtain fine grained dense bioceramics. The samples sintered at 1200  C, with a density near the theoretical one, were composed of micron-sized grains, while the grain size decreased to 130 nm on decreasing the sintering temperature to 900  C. This decrease in the grain size certainly led to increases in the fracture toughness by much as 54%. An in vitro investigation of biocompatibility with L929 and human MRC-5 fibroblast cells showed noncytotoxic effects for both types of bioceramics, while the relative cell prolifera- tion rate, cell attachment and metabolic activity of the fibro- blasts were improved with decreasing of grain size. An initial in vivo investigation of biocompatibility by the primary cuta- neous irritation test showed that both materials exhibited no irritation properties. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2012. Key Words: hydroxyapatite, microwave sintering, fracture toughness, cell proliferation, biocompatibility How to cite this article: Veljovic ´ D, C ˇ olic ´ M, Kojic ´ V, Bogdanovic ´ G, Kojic ´ Z, Banjac A, Palcevskis E, Petrovic ´ R, Janac ´ kovic ´ D. 2012. The effect of grain size on the biocompatibility, cell–materials interface, and mechanical properties of microwave-sintered bioceramics. J Biomed Mater Res Part A 2012:00A:000–000. INTRODUCTION Different forms of hydroxyapatite (HAP) bioceramics have received considerable attention as suitable materials for the manufacture of osseous implants. Dense HAP implant mate- rials with adequate mechanical properties are often used in maxillofacial, dental and orthopedic surgery. HAP-based materials in tooth form, have been used as an immediate tooth root replacement to minimize alveolar ridge resorp- tion, which follows tooth loss, and to maintain ridge width and height. In particulate form, dense hydroxyapatite is used in maxillofacial surgery as individual implants, as well as a filler in bony defects and as a filler in association with the placement of metal implants in orthopedic practice, as part of complex systems for hip replacements, etc. 1–4 Opti- mal properties of the starting powder, correct selection of the sintering technique and processing conditions, careful control of the phase composition and microstructure in ac- cordance with good mechanical properties and biocompati- bility can be key prerequisites for a high-quality implant material. 5–7 Generally, the brittle nature, low-fracture tough- ness, and hardness of sintered HAP-based bioceramics, con- ventionally processed for long holding times at high sinter- ing temperatures, often limit the use of these materials in some load-bearing clinical applications. 8–10 Appreciable improvements in the mechanical properties of HAP-based bioceramic materials were achieved through control of the grain size, pore size, and shapes, by the addition of different tougher and fibrous particles in the HAP matrix, etc. 6,11–15 Microwave sintering shows great potential for the proc- essing of bioceramics, with a series of benefits, such as lower sintering temperatures and shorter processing times, a high degree of control over the microstructure, no thermal gradient, no limit of the geometry of the products, uniform microstructures of materials with limited grain growth, etc. 16–19 Limiting of grain growth may provoke significant improvements of the mechanical and nanomechanical prop- erties, mainly in fracture toughness and hardness of biocer- amic materials. 20–23 Correspondence to: Dj. Veljovic ´ ; e-mail: djveljovic@tmf.bg.ac.rs V C 2012 WILEY PERIODICALS, INC. 1