In vitro changes in the structure of a bioactive calcia–silica sol–gel glass explored using isotopic substitution in neutron diffraction R.J. Newport a, * , L.J. Skipper a , V. FitzGerald a , D.M. Pickup a , M.E. Smith b , J.R. Jones c a School of Physical Sciences, University of Kent, Canterbury CT2 7NH, UK b Department of Physics, University of Warwick, Coventry CV4 7AL, UK c Department of Materials, Imperial College, London SW7 2AZ, UK Available online 26 March 2007 Abstract Bioactive sol–gel derived glass scaffolds bond to bone and their dissolution products stimulate new bone growth in vitro and in vivo; they may therefore be used to regenerate diseased or damaged bone to its original state and function in bone tissue engineering appli- cations. We seek herein to cast light upon these reaction mechanisms by attempting to quantify changes in the atomic-scale structure of the glass scaffold as a result of in vitro reaction with simulated body fluid (SBF). We report the results of a study using neutron diffraction with isotopic substitution (NDIS) to gain new insights into the nature of the atomic scale calcium environment in bioactive sol–gel glasses. This is augmented by high-energy X-ray total diffraction. We have thereby begun to explore the nature of the principal stages to the generation of hydroxyapatite (i.e. the mineral ‘building block’ of bone) on the bioactive glass surface. The data are examined in light of our complementary solid-state NMR and computer modelling studies. The results reveal that the Ca–O environment in an SBF exposed (CaO) 0.3 (SiO 2 ) 0.7 sol–gel glass, which initially comprises three distinct but partially overlapping correlation shells centered at 2.3 A ˚ , 2.5 A ˚ and 2.75 A ˚ , preferentially loses the shortest length correlation. A CaH correlation appears at 2.95 A ˚ . The surface depos- ited CaP environment consists of three partially overlapping, but nonetheless distinct, correlation shells, at 3.15 A ˚ , 3.40 A ˚ and 3.70 A ˚ . Ó 2007 Elsevier B.V. All rights reserved. PACS: 61.43.Fs; 61.12.Ld; 61.10.Nz; 61.10.Ht; 61.18.j Keywords: Bioglass; Biomaterials; Neutron diffraction/scattering; Silicates; Sol–gels (xerogels); Short-range order 1. Introduction Biomaterials research links many disciplines, with the common goal to repair, augment or replace damaged or diseased tissue. A large number of biomaterials have been developed, suitable for a range of biomedical applications. Bioactive glasses are one such family of materials, and are of interest due to their ability to bond to bone; their disso- lution products stimulate new bone growth in vitro and in vivo. They may therefore be used to regenerate diseased or damaged bone to its original state and function in bone tissue engineering applications. Since the discovery of the first bioactive silicate glass system, Na 2 O–CaO–P 2 O 5 – SiO 2 (Bioglass Ò ) in 1971 by Hench, interest has grown in glasses and ceramics with simpler compositions due to the discovery that only soluble silicon and calcium ions aid in the tissue regeneration process by stimulation of the appropriate genes [1]. The sol–gel method of glass production is widely used because it permits the fabrication of oxide materials under relatively mild conditions and with a wide range of adjust- able experimental parameters. Sol–gel derived calcia:silica glasses, (CaO) x (SiO 2 ) 1x , have been found to have a relatively enhanced bioactivity, along with a controllable porous structure, which makes them of particular interest in the field of biomaterials [2,3]. In an earlier paper, we describe the atomic-scale structure of the glass, and offer initial insight into the reaction mechanisms when the glass 0022-3093/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jnoncrysol.2007.02.015 * Corresponding author. Tel.: +44 (0)1227 827887; fax: +44 (0)1227 827558. E-mail address: r.j.newport@kent.ac.uk (R.J. Newport). www.elsevier.com/locate/jnoncrysol Journal of Non-Crystalline Solids 353 (2007) 1854–1859