Please cite this article in press as: Gandolfi MG, et al. Osteoinductive potential and bone-bonding ability of ProRoot MTA, MTA Plus and Biodentine in rabbit intramedullary model: Microchemical characterization and histological analysis. Dent Mater (2017), http://dx.doi.org/10.1016/j.dental.2017.01.017 ARTICLE IN PRESS DENTAL-2912; No. of Pages 18 d e n t a l m a t e r i a l s x x x ( 2 0 1 7 ) xxx.e1–xxx.e18 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.intl.elsevierhealth.com/journals/dema Osteoinductive potential and bone-bonding ability of ProRoot MTA, MTA Plus and Biodentine in rabbit intramedullary model: Microchemical characterization and histological analysis M.G. Gandolfi a,b,∗ , G. Iezzi c , A. Piattelli c , C. Prati b , A. Scarano c a Laboratory of Biomaterials and Oral Pathology, Dental School, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy b Endodontic Clinical Section, Dental School, Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy c Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti Scalo, Italy a r t i c l e i n f o Article history: Received 8 March 2016 Received in revised form 10 January 2017 Accepted 31 January 2017 Available online xxx Keywords: Hydraulic calcium silicate cements ProRoot MTA MTA Plus Biodentine Osteoinduction Bone-bonding (bioactivity) Mineralization degree Ca/P ratio Ca/N ratio P/N ratio a b s t r a c t Objective. To study the in vivo osteoinductive potential, bone-bonding ability (bioactivity) and bone biomineralization of current hydraulic calcium silicate cements used as graft materials and placed in contact with medullary bone. Methods. ProRoot MTA, MTA Plus and Biodentine were used to fill surgical bone defects (2- mm diameter through the entire cortical thickness to reach the medullary bone) in the tibia of mature male rabbits. Tibiae were retrieved after 30 days and submitted to histological analysis and microchemical characterization using Optical Microscopy (OM) and Environ- mental Scanning Electron Microscopy with Energy Dispersive X-ray analysis (ESEM-EDX). Bone neoformation and histomorphometric evaluations, degree of mineralization (by Ca/P, Ca/N and P/N ratios) and the diffusion of material elements were studied. Results. Bone neoformation was observed in response to all materials. No sign of necrosis were found on the walls of the pre-existing cortical bone. No osteoclasts and no formation of fibrous tissue were evident. Sign of angiogenesis were present. EDX (element content, line profile and element mapping) showed the increase in Ca and P and decrease in C, S and N from the mature bone towards the mineralizing interface. Ca/P, Ca/N and P/N ratios showed differences in the degree of mineralization/maturation stage of bone. MTA Plus and ProRoot MTA exhibited close contact with the pre-existing bone and good bone-bonding with neoformed bone juxtaposed on the medullary side of the materials with- out interposed connective tissue or resorption lacunae or gaps. The materials showed a dense appearance with 100% of residual materials and no colonization by fluids and cells. No migration of Bi or Al material elements to the newly formed bone was found. Biodentine showed newly formed trabecular bone with marrow spaces and sparse traces of residual material (≈9%). Significance. The in vivo osteoinductive properties with dynamic biomineralization processes around these calcium silicate materials extruded in medullary bone in appropriate animal ∗ Corresponding author. E-mail address: mgiovanna.gandolfi@unibo.it (M.G. Gandolfi). http://dx.doi.org/10.1016/j.dental.2017.01.017 0109-5641/© 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.