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 applications. 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)(SiO2)(0.7) sol-gel glass, which initially comprises three distinct but partially overlapping correlation shells centered at 2.3 angstrom, 2.5 angstrom and 2.75 angstrom, preferentially loses the shortest length correlation. A (CaH)-H-. correlation appears at 2.95 angstrom. The surface deposited (CaP)-P-. environment consists of three partially overlapping, but nonetheless distinct, correlation shells, at 3.15 angstrom, 3.40 angstrom and 3.70 angstrom. (c) 2007 Elsevier B.V. All rights reserved.