This work reports the synthesis of lithium-silicate glass, containing 10 mol% of Li 2 O by the sol-gel process, intended for the regeneration of cartilage. Lithium citrate and lithium nitrate were selected as lithium precursors. The effects of the lithium precursor on the sol-gel process, and the resulting glass structure, morphology, dissolution behaviour, chondrocyte viability and proliferation, were investigated. When lithium citrate was used, mesoporous glass containing lithium as a network modifier was obtained, whereas the use of lithium nitrate produced relatively dense glass-ceramic with the presence of lithium metasilicate, as shown by X-ray diffraction, 29 Si and 7 Li MAS NMR and nitrogen sorption data. Nitrate has a better affinity for lithium than citrate, leading to heterogeneous crystallisation from the mesopores, where lithium salts precipitated during drying. Citrate decomposed at a lower temperature, where the crystallisation of lithium-silicate crystal is not thermodynamically favourable. Upon decomposition of the citrate, a solid-state salt metathesis reaction between citrate and silanol occurred, followed by the diffusion of lithium within the structure of the glass. Both glass and glass-ceramic released silica and lithium ions in culture media, but release rate was lower for the glass-ceramic. Both samples did not affect chondrocyte viability and proliferation.Graphical Abstract

Wnt-signalling cascade is one of the crucial pathways involved in the development and homeostasis of cartilage. Influencing this pathway can potentially contribute to improved cartilage repair or regeneration. One key molecular regulator of the Wnt pathway is the glycogen synthase kinase-3 (GSK-3) enzyme, the inhibition of which allows initiation of the signalling pathway. This study aims to utilise a binary SiO2 -Li2O sol-gel derived glass for controlled delivery of lithium, a known GSK-3 antagonist. The effect of the dissolution products of the glass on chondrogenic differentiation in an in vitro 3-D pellet culture model is reported. Dissolution products that contained 5 mM lithium and 3.5 mM silicon, were capable of inducing chondrogenic differentiation and hyaline cartilaginous matrix formation without the presence of growth factors such as TGF-β3. The results suggest that sol-gel derived glass has the potential to be used as a delivery vehicle for therapeutic lithium ions in cartilage regeneration applications.

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To further improve the understanding of in vitro biological effects of incorporated radionuclides, it is essential to accurately determine cellular absorbed doses. In the case of fi emitters, the cross-dose is a major contribution, and can involve up to millions of cells. Realistic and efficient computational models are needed for that purpose. Conventionally, distances between each cell are calculated and the related dose contributions are cumulated to get the total cross-dose (standard method). In this work, we developed a novel approach for the calculation of the cross-absorbed dose, based on the use of the radial distribution function (rdf)) that describes the spatial properties of the cellular model considered. The dynamic molecular tool LAMMPS was used to create 3D cellular models and compute rdfs for various conditions of cell density, volume size, and configuration type (lattice and randomized geometry). The novel method is suitable for any radionuclide of nuclear medicine.Here, the model was applied for the labelling of cells with 18 F-FDG used for PET imaging, and first validated by comparison with other reference methods. Mean Scross values calculated with the novel approach versus the standard method agreed very well (relative differences less that 0.1%).Implementation of the rdf-based approach with LAMMPS allowed to achieved results considerably faster than with the standard method, the computing time decreasing from hours to seconds for 106 cells. The rdf-based approach was also faster and easier to accommodate more complex cellular models than the standard and other published methods. Finally, a comparative study of the mean Scross for different types of configuration was carried out, as a function of the cell density and the volume size, allowing to better understand the impact of the configuration on the cross-absorbed dose.

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