Antonio Tilocca

Molecular dynamics simulations reveal the importance of using dynamical descriptors to rationalize and predict the behavior of biomedical glasses.

In the past ten years, the application of molecular dynamics simulations in the field of bioactive glasses has improved our fundamental understanding of composition–bioactivity relationships and reactivity in these materials. The present chapter summarizes these applications by illustrating some of their main achievements, from identifying structural features that control the biological behaviour of the glass, to rationalising the dependence of these features on the composition, to modelling some of the dynamical processes (surface adsorption, hydrolysis, alkali depletion, ion migration) that unfold once the material is set in contact with a physiological environment.

Understanding how calcium interacts with silica sources and influences their polycondensation in aqueous solutions is of central importance for the development of more effective biomaterials by sol–gel approaches. For this purpose, the atomic-scale evolutions of a calcium-containing precursor solution corresponding to a typical sol–gel bioactive glass and of a corresponding Ca-free solution were compared using reactive molecular dynamics simulations. The simulations highlight a significantly faster rate of condensation when calcium is present in the initial solution, resulting in the formation of large and ramified silica clusters within 5 ns, which are absent in the Ca-free system. This different behavior has been analyzed and interpreted in terms of the Ca-induced nanosegregation in calcium-rich and silica-rich regions, which promotes the condensation reactions within the latter. By identifying a possible mechanism behind the limited incorporation of calcium in the silica nanoclusters formed in the early stages of the sol–gel process, these results could guide further studies aimed at identifying favorable experimental conditions to enhance initial calcium incorporation and thus produce sol–gel biomaterials with improved properties.

Molecular dynamics simulations of two glass nanoparticles with composition 25Na2O·25CaO 50SiO2 mol% (Ce-K NP) and 46.1SiO2·24.4Na2O·26.9CaO· 2.6P2O5 mol.% (Ce-BG NP) doped with 3.6 mol% of CeO2 have been carried out in order to explain the enhanced antioxidant properties of the former glass with respect to the latter.The present models show that the different catalase mimetic activity of the two NPs is related to the Ce3+/Ce4+ ratio exposed at their surface. In fact, this ratio is about 3.5 and 13 in the bulk and at the surface of the Ce-BG NP, and 1.0 and 2.1 in the bulk and at the surface of the Ce-K NPs, respectively. Since both oxidation states are necessary for the catalysis of the dismutation reaction of hydrogen peroxides, NPs with a very high Ce3+/Ce4+ ratio possess poorer antioxidant properties.Moreover, our simulations reveal that the already low silicate connectivity found in the bulk glasses examined here is further reduced on the nanoparticle surface, whereas the Na+/Ca2+ ratio rapidly increases. Sodium, calcium and cerium sites in proximity of the surface are found to be under-coordinated, prone to quickly react with water present in physiological environments, thus accelerating the glass biodegradation

The dissolution of fluoride-containing bioactive glasses critically affects their biomedical applications. Most commercial fluoride-releasing bioactive glasses have been designed in the soda–lime–silica system. However, their relatively slow chemical dissolution and the adverse effect of fluoride on their bioactivity are stimulating the study of alternative biodegradable materials with higher biodegradability, such as biodegradable phosphate-based bioactive glasses, which can be a good candidate for applications where a fast release of active ions is sought. In order to design new biomaterials with controlled degradability and high bioactivity, it is essential to understand the connection between chemical composition, molecular structure, and solubility in physiological fluids. Accordingly, in this work we have combined the strengths of various experimental techniques with Molecular Dynamics (MD) simulations, to elucidate the impact of fluoride ions on the structure and chemical dissolution of bioactive phosphate glasses in the system: 10Na₂O–(45 − x)CaO–45P₂O₅–xCaF₂, where x varies between 0–10 mol%. NMR and MD data reveal that the medium-range atomic-scale structure of these glasses is dominated by Q² phosphate units followed by Q¹ units, and the MD simulations further show that fluoride tends to associate with network modifier cations to form alkali/alkaline-earth rich ionic aggregates. The impact of fluoride on chemical dissolution of glasses has been studied in deionized water, acidic (pH = 3.0), neutral (pH = 7.4) and basic (pH = 9.0) buffer solutions, while the bioactivity and cytotoxicity of glasses has been studied in vitro through their apatite-forming ability in simulated body fluid (SBF) and cell culture tests on mesenchymal stem cells (MSCs), respectively. The macroscopic trends observed from various chemical dissolution and bioactivity studies are discussed on the basis of the effect of fluoride on the atomistic structure of glasses, such as F-induced phosphate network re-polymerization, in an attempt to establish composition–structure–property relationships for these biomaterials.

Molecular dynamics simulations of Na ⁺ /H ⁺ -exchanged 45S5 Bioglass® reveal the co-existence of bonded and non-bonded hydroxyls, suggesting a direct mechanism for forming a silica-rich gel structure upon the initial ion exchange.