Hydroxyapatite/SiO 2 –CaO–P 2 O 5 glass materials: In vitro bioactivity and biocompatibility S. Padilla, J. Roma ´n, S. Sa ´nchez-Salcedo, M. Vallet-Regı ´ * Departamento de Quı ´mica Inorga ´ nica y Bioinorga ´ nica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain Received 6 September 2005; received in revised form 22 December 2005; accepted 25 January 2006 Abstract Materials obtained by the heat treatment of mixtures of hydroxyapatite (HA) and a silicate-based glass of the system SiO 2 –CaO–P 2 O 5 have been investigated. The influence of the glass content on the porosity, microstructure and on the constituent phases of the final mate- rials was studied. The influence of these factors on the in vitro bioactive behaviour of the obtained materials was also investigated. In addition, an in vitro biocompatibility assay with osteoblastic-like cells was carried out. The addition of the glass to HA induced different solid-state reactions that yield the transformation of HA into a- and b-tricalcium phosphate as well as the formation of silicon-containing phases (silicocarnotite or pseudowollastonite). In these mixtures an enhancement in the porosity, pore size and a heterogeneous micro- structure was observed, compared with the precursors. As the sol gel glass content increased, the previous effects were higher. The mate- rials showed the formation of an apatite-like layer on their surface when soaked in simulated body fluid, being faster in the sample with a higher content of glass. The formation of the new layer began in preferential zones in both samples, depending on the different reactivity of the crystalline phases formed. A synergistic effect between HA and glass was observed, showing in the mixtures a faster bioactive behaviour than in HA and glass themselves. The obtained materials allow a good attachment, spread and proliferation of the osteoblas- tic-like cells and no cytotoxic effect was observed. Ó 2006 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Calcium phosphate materials and hydroxyapatite (HA), in particular, seem to be ideally suited to be bone implants, because of their similarity to the chemical composition of osseous tissues, their biocompatibility, lack of inflamma- tory response, and osteoconductive capacity. HA allows a specific biological response in the tissue–implant interface, which leads to the formation of bonds between the bone and the materials (bioactivity) [1]. However, although HA is bioactive it shows a limited in vitro reactivity [2] and in vivo assays have shown slow formation of osseous tissue [3]. Other materials such as bioactive silicate-based glasses [4] show a higher bioactive behaviour than calcium phos- phate materials [1,5]. For instance, the bioactivity reactions in silica-based glasses occur in a few minutes [6], whereas those in HA take several days [5]. A very important char- acteristic of the silica-based glasses is that they show a genetic control of the cellular response of osteoblasts. It has been observed that different genes are up regulated within 48 h of exposure of primary human osteoblasts to the ionic dissolution products of bioactive glasses [7]. The rapid bioactive behaviour of these silica-based glasses has been related to the role of SiO 2 or silicon in their surface reactions and therefore on their in vivo and in vitro behav- iour. The surface reactions that occur in the bioactive glasses allow the subsequent crystallization of apatite crys- tals, cell adhesion and collagen formation [8,9]. Silicon is believed to be essential in skeletal development; the first indications of a physiological role for silicon were reported by Carlisle [10], who observed that silicon was involved in the early stage of bone calcification. Schwarz and Milne 1742-7061/$ - see front matter Ó 2006 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.actbio.2006.01.006 * Corresponding author. Tel.: +34 91 3941861; fax: +34 91 3941786. E-mail address: vallet@farm.ucm.es (M. Vallet-Regı ´). Acta Biomaterialia 2 (2006) 331–342 www.actamat-journals.com