Role of the Short Distance Order in Glass Reactivity

In 2005, our group described for the first time the structural characterization at the atomic scale of bioactive glasses and the influence of the glasses’ nanostructure in their reactivity in simulated body fluids. In that study, two bioactive sol-gel glasses with composition 80%SiO2–20%CaO and 80%SiO2–17%CaO–3%P2O5 (in mol-%) were characterized by High-Resolution Transmission Electron Microscopy (HRTEM). Such characterization revealed unknown features of the glasses’ structure at the local scale that allowed the understanding of their different in vitro behaviors as a consequence of the presence or absence of P2O5. Since then, the nanostructure of numerous bioactive glasses, including melt-prepared, sol-gel derived, and mesoporous glasses, was investigated by HRTEM, Nuclear Magnetic Resonance (NMR) spectroscopy, Molecular Dynamics (MD) simulations, and other experimental techniques. These studies have shown that although glasses are amorphous solids, a certain type of short distance order, which greatly influences the in vitro and in vivo reactivity, is always present. This paper reviews the most significant advances in the understanding of bioactive glasses that took place in the last years as a result of the growing knowledge of the glasses’ nanostructure

Glasses in bone regeneration: A multiscale issue

3D scaffolds based in mesoporous bioactive glasses (MBGs) are being widely investigated to use in bone tissue engineering (TE) applications. These scaffolds are often obtained by rapid prototyping (RP) and exhibit an array of interconnected pores in a hierarchy of sizes. The ordered mesopore network (around 4 nm in diameter) is optimal for the adsorption and release of bone inductor biomolecules, and the arrangement of macropores over 100 mu m facilitates the bone cell ingrowths and angiogenesis. Nevertheless MBG composition can be varied almost infinitely at the atomic scale by including in the glass network oxides of inorganic elements with a therapeutic action. In this article the synthesis and characterization of MBG scaffolds based on the 80%SiO2-15%CaO-5%P2O5 (in mol-%) glass with substitutions up to 3.5% of Ga2O3 or Ce2O3 or 7.0% of ZnO are revisited. The substituent inclusion and the RP processing slightly decrease the surface area, the pore volume and the mesoporous order as well as their bioactive response in solutions mimicking blood plasma. However, these values still remain useful for bone TE applications. Results exhibiting the bactericide action of MBG scaffolds containing ZnO are also presented. (C) 2015 Elsevier B.V. All rights reserved

Tailoring the Structure of Bioactive Glasses: From the Nanoscale to Macroporous Scaffolds

Bioactive glasses have played a very important role in the development of new materials for bone tissue regeneration. The development of new synthesis and manufacturing methods allows the preparation of bioactive glasses with new chemical compositions, nanoscaled features, customized morphologies, and pore architectures. The composition of glasses can be designed at the atomic-molecular level to ensure bioactivity and beneficial effects including capabilities for enhancing osteogenesis and vascularization or to exert bactericide action. Moreover, the glasses can be prepared as mesoporous bioactive glasses, exhibiting ordered arrangements of nanometric pores. Through the control of the microstructure, glasses can be prepared to achieve suitable interactions with living cells. Finally, the scaffolds obtained with bioactive glasses must display interconnected pores over 100 m to make possible bone cell ingrowths and angiogenesis. In this article, the advances in the field of bioactive glasses through the control of the chemical, nanometer scale, microstructural properties, and architectural features are presented and discussed. A detailed control of these four levels of matter organization will allow optimizing the biological response of bioactive glasses when used in bone tissue regeneration

Mesoporous bioglasses enriched with bioactive agents for bone repair, with a special highlight of Maria Vallet-Regi´s contribution

Throughout her impressive scientific career, Prof. María Vallet-Regi opened various research lines aimed at designing new bioceramics, including mesoporous bioactive glasses for bone tissue engineering applica-tions. These bioactive glasses can be considered a spinoff of silica mesoporous materials because they are designed with a similar technical approach. Both materials exhibit ordered mesoporous structures with a very narrow pore size distribution that are achieved by using surfactants during their synthesis. In aqueous solutions the surfactants form mesophases behaving as directing structure agents and after being removed by calcination or extraction the mesoporous bioactive glasses are obtained. The characteristics of these ma-terials made them suitable to be enriched with various osteogenic agents, namely inorganic ions and bio-peptides as well as mesenchymal cells. In the present review, we summarize the evolution of mesoporous bioactive glasses research for bone repair, with a special highlight on the impact of Prof. Maria Val-let-Regi´s contribution to the field

Mesoporous silica nanoparticles as a new carrier methodology in the controlled release of the active components in a polypill

Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12.5/2.5/25/40 weight ratio. The procedure is based onmesoporous silica nanoparticles (MSN) with MCM-41 structure (MSN-41) used as carrier, aimed to control release of the four drugs included in the polypill. In vitro release data were obtained by HPLC and the curves adjusted with a kinetic model. To explain the release results, a molecular model was built to determine the drug-matrix interactions, and quantum mechanical calculations were performed to obtain the electrostatic properties of each drug. Amlodipine, losartan and simvastatin were released from the polypill-MSN-41 system in a controlled way. This would be a favourable behavior when used clinically because avoid too quick pressure decrease. However, the diuretic hydrochlorothiazide was quickly released from our system in the first minutes, as is needed in hypertensive urgencies. In addition, an increase in the stability of amlodipine and hydrochlorothiazide occurred in the polypill-MSN-41 system. Therefore, the new way of polypill dosage proposed can result in a safer and effective treatment. (C) 2016 Elsevier B.V. All rights reserved

A molecular model to explain the controlled release from SBA-15 functionalized with APTES

A molecular model with the approximate pore diameter of SBA-15 was constructed for the first time to investigate the effect of functionalize the matrix with 3-aminopropyl-triethoxy-silane (APTES) in the release of Chicago Sky Blue 6B (CSB). It was expected that the positively charged amino groups of APTES could interact with the negatively charged sulphonic groups of CSB allowing controlling the release process. Indeed the experimental study showed that the release kinetics of CSB from SBA-15-APTES is two orders of magnitude smaller than from native SBA-15. However molecular modelling calculations investigating the possible interactions of APTES and SBA-15 yield unexpected results. In the model including only the condensation between the silanol groups of SBA-15 and APTES, the calculated interaction energy of CSB was quite similar than with the model of native SBA-15. However when additional electrostatic interactions of the -NH2 groups of APTES with the mesoporous matrix were modelled the mesoporous channels underwent a considerable deformation. These results point to the structure deformation as the cause of the greater retention of CSB in SBA-15-APTES and warn about the special features of AFTES when used to functionalize mesoporous silica materials. The model built in this paper could be used to construct predictive models in analogous drug delivery systems. (C) 2014 Elsevier Inc. All rights reserved

Mesoporous bioactive glasses for regenerative medicine.

Stem cells are the central element of regenerative medicine (RM). However, in many clinical applications the use of scaffolds fabricated with biomaterials is required. In this sense, mesoporous bioactive glasses (MBGs) are going to play an important role in bone regeneration because their striking textural properties, quick bioactive response and biocompatibility. As the other bioactive glasses, MBGs are mainly formed by silicon, calcium and phosphorus oxides whose ions play an important role in cell proliferation as well as in homeostasis and bone remodeling process. A common improvement of bioactive glasses for RM is by adding small amounts of oxides of elements that confer them additional biological capacities, including osteogenic, angiogenic, antibacterial, anti-inflammatory, haemostatic or anticancer properties. Moreover, MBGs are versatile in terms of the different ways in which they can be processed such as scaffolds, fibers, coatings or nanoparticles. MBGs are unique because their textural properties are so high that they still exhibit outstanding bioactive responses even after adding extra inorganic ions or being processed as scaffolds or nanoparticles. Moreover, they can be further improved by loading with biomolecules, drugs and stem cells. This article reviews the state of the art and future perspectives of MBGs in the field of RM of hard tissues

Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis

Objectives: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. Material and methods: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables. A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable. Results: The study identified 13 (26%) VHL mutations related to nuclear grade (P = 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P = 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P<0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P<0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P<0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P = 0.014). Conclusions: VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages

Novel ion-doped mesoporous glasses for bone tissue engineering: Study of their structural characteristics influenced by the presence of phosphorous oxide

Ion-doped binary SiO2-CaO and ternary SiO2-CaO-P2O5 mesoporous bioactive glasses were synthesized and characterized to evaluate the influence of P2O5 in the glass network structure. Strontium, copper and cobalt oxides in a proportion of 0.8 mol% were selected as dopants because the osteogenic and angiogenic properties reported for these elements. Although the four glass compositions investigated presented analogous textural properties, TEM analysis revealed that the structure of those containing P2O5 exhibited an increased ordered mesoporosity. Furthermore, 29Si NMR revealed that the incorporation of P2O5 increased the network connectivity and that this compound captured the Sr2 +, Cu2 + and Co2 + ions preventing them to behave as modifiers of the silica network. In addition, 31P NMR results revealed that the nature of the cation directly influences the characteristics of the phosphate clusters. In this study, we have proven that phosphorous oxide entraps doping-metallic ions, granting these glasses with a greater mesopores order