Daniel Arcos

Sol–gel silica-based biomaterials and bone tissue regeneration

The impact of bone diseases and trauma in developed and developing countries has increased significantly in the last decades. Bioactive glasses, especially silica-based materials, are called to play a fundamental role in this field due to their osteoconductive, osteoproductive and osteoinductive properties. In the last years, sol-gel processes and supramolecular chemistry of surfactants have been incorporated to the bioceramics field, allowing the porosity of bioglasses to be controlled at the nanometric scale. This advance has promoted a new generation of sol-gel bioactive glasses with applications such as drug delivery systems, as well as regenerative grafts with improved bioactive behaviour. Besides, the combination of silica-based glasses with organic components led to new organic-inorganic hybrid materials with improved mechanical properties. Finally, an effort has been made to organize at the macroscopic level the sol-gel glass preparation. This effort has resulted in new three-dimensional macroporous scaffolds, suitable to be used in tissue engineering techniques or as porous pieces to be implanted in situ. This review collects the most important advances in the field of silica glasses occurring in the last decade, which are called to play a lead role in the future of bone regenerative therapies.

Silicon substituted hydroxyapatites. A method to upgrade calcium phosphate based implants

Silicon substituted hydroxyapatites (SiHA) are among the most interesting bioceramics in the field of bioactive bone implants. Silicon incorporation into the apatite structure results in materials with comparable biocompatibility and mechanical properties, but with improved bioactive behaviour. The higher bioactivity promotes the reaction between bone and implant, leading to excellent osteointegration and ensuring the implant success. The improved properties of SiHA compared to pure HA have been demonstrated by both in vitro and in vivo tests. In this feature article, the main synthesis methods and results are reviewed for different SiHA. Finally, the role of Si is considered from the point of view of materials science at the crystallographic, micro structural and surface chemistry levels.

A unified in vitro evaluation for apatite-forming ability of bioactive glasses and their variants

The aim of this study was to propose and validate a new unified method for testing dissolution rates of bioactive glasses and their variants, and the formation of calcium phosphate layer formation on their surface, which is an indicator of bioactivity. At present, comparison in the literature is difficult as many groups use different testing protocols. An ISO standard covers the use of simulated body fluid on standard shape materials but it does not take into account that bioactive glasses can have very different specific surface areas, as for glass powders. Validation of the proposed modified test was through round robin testing and comparison to the ISO standard where appropriate. The proposed test uses fixed mass per solution volume ratio and agitated solution. The round robin study showed differences in hydroxyapatite nucleation on glasses of different composition and between glasses of the same composition but different particle size. The results were reproducible between research facilities. Researchers should use this method when testing new glasses, or their variants, to enable comparison between the literature in the future.

Magnetic mesoporous silica spheres for hyperthermia therapy.

Magnetic nanoparticles coated with materials having unique properties, such as ordered pore structures and large surface areas, hold great potential for multimodal therapies. This study reports on the biocompatibility of composites of maghemite nanoparticles embedded in an ordered mesoporous silica-matrix to form magnetic microspheres (MMS), and on their ability to conduct magnetic hyperthermia upon exposure to a low-frequency alternating magnetic field (AMF). MMS particles were efficiently internalized by human A549, Saos-2 and HepG2 cells, and were excluded from the nuclear compartment. MMS treatment did not interfere with morphological features or metabolic activities of the cells, indicating good biocompatibility of the material. MMS did not affect the endogenous heat-shock response of a HeLa-derived cell line that precisely reports the intensity of thermal stresses through changes in the activities of a stably integrated hsp70B promoter and a constitutive viral promoter. Maximum temperature in MMS suspensions increased to a range above 42°C as a function of the amounts of particles exposed to AMF. Cell culture experiments showed that, by adjusting the amount of MMS and the time of exposure to AMF, heat treatments of mild to very high intensities could be achieved. Cell viability dropped as a function of the intensity of the heat treatment achieved by MMS and AMF exposures. The possibility of fine-tuning the heating power output, together with efficient uptake by tumor cells in vitro, makes MMS a promising agent by which to provide hyperthermia treatments aimed toward remission of solid tumors.

Interaction of an ordered mesoporous bioactive glass with osteoblasts, fibroblasts and lymphocytes, demonstrating its biocompatibility as a potential bone graft material

Ordered mesoporous 85SiO(2)-10CaO-5P(2)O(5) bioactive glass (MBG85) is an excellent candidate as a graft for bone tissue regeneration, owing to its excellent textured properties, structural characteristics and crystalline apatite rate formation. To assess MBG85 biocompatibility, different parameters have been evaluated (cell morphology, size/complexity, proliferation, viability, cell cycle, reactive oxygen species content, lactate dehydrogenase release) using human Saos-2 osteoblasts after treatment with either MBG85 extracts or 1% MBG85 directly added to cells. The osteoblast response to MBG85 was compared with L929 fibroblast behaviour after the same treatment. The high cell viability observed and the absence of signs of cell damage in both cell types demonstrates MBG85 biocompatibility. Only a cytostatic effect was observed through the reduction of cell proliferation, related with the initial Ca elution, whereas Si leaching did not result into any negative effect. In vitro lymphocytic proliferation analysis was also carried out with SR.D10 clone after treatment with either MBG85 extracts or culture supernatants of L929 fibroblasts previously treated with 1% MBG85 (cell-conditioned extracts). The absence of modification of in vitro T-cell response underlines the biocompatibility of MBG85 and its potential application in the field of bone and dental grafting.

A novel bioactive and magnetic biphasic material.

A novel biphasic material has been synthetised from a sol-gel-derived glass (Si-Ca-P) and a glass-ceramic obtained from a melt-derived glass (Si-Ca-Fe). Both components of such a biphasic mixture are bioactive, but with different kinetics for the growth of an apatite-like layer on the surface of these materials, needing only one day for the sol-gel-derived glass and one month for the glass-ceramic. The glass-ceramic shows magnetic properties. The biphasic material, obtained from a mixture 1:1 of these components, is bioactive, and its surface is coated after 15 days of soaking in SBF. The biphasic material also exhibited magnetic behaviour, useful for hyperthermia.

Functionalizing Mesoporous Bioglasses for Long‐Term Anti‐Osteoporotic Drug Delivery

Mesoporous bioactive glasses (MBGs) associated with an anti-osteoporotic drug (ipriflavone) have been prepared. With this aim, MBGs were functionalised with different organic groups by following a post-grafting method, thus retaining the mesoporous network of the bioactive substrates. Drug-delivery tests were carried out by using ipriflavone as a hydrophobic model drug. Our results revealed that by means of the proper functionalisation, most of the drug is retained in the mesoporous network. By tailoring the hydrophobicity of the surface with functional groups, the drug-material link can be tuned, thereby ensuring the long-term delivery of ipriflavone. In vitro bioactive tests demonstrate that these systems exhibit the same excellent behaviour of non-functionalised MBGs. The possibility to add a bone resorption inhibitor such as ipriflavone to highly bioactive materials confirms functionalised MBGs as very promising bone-tissue regeneration systems.

Evolution of porosity during in vitro hydroxycarbonate apatite growth in sol‐gel glasses

A bioactive glass of composition (mol %) SiO(2) 58, CaO 36, P(2)O(5) 6 was obtained using the sol-gel method. Changes in porosity during the growth of a hydroxycarbonate apatite (HCA) phase were studied at different stages of the process. The high Ca (II) content led to a higher degree of porosity and enhancement of Ca(2+) released from surface and bulk when the glass was soaked into simulated body fluid (SBF). Saturation of the media (SBF) together with the porosity of the material led to fast growth of HCA on the surface and into the pores.

Promising trends of bioceramics in the biomaterials field

Biomedical scientific community is currently demanding new advances in the designing of 3rd generation bioceramics, which promote bone tissue regeneration. In the last years, the development of supramolecular chemistry and the application of organic-inorganic hybrid materials in the biomedical field have resulted in a new generation of advanced bioceramics, which exhibit fascinating properties for regenerative purposes together with the possibility of being used as carriers of biologically active molecules. This communication overviews the evolution occurred from the first silica based bioceramics to the last advances in the synthesis of bioceramics for bone tissue regeneration. A critical review concerning the first bioactive glasses as well as the newest hybrid bioactive materials and templated mesoporous bioactive systems, will be performed from the point of view of their potential applications as replacement materials in bone repair and regeneration.

Local structures of mesoporous bioactive glasses and their surface alterations in vitro: inferences from solid-state nuclear magnetic resonance

We review the benefits of using 29Si and 1H magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy for probing the local structures of both bulk and surface portions of mesoporous bioactive glasses (MBGs) of the CaO–SiO2−(P2O5) system. These mesoporous materials exhibit an ordered pore arrangement, and are promising candidates for improved bone and tooth implants. We discuss experimental MAS NMR results from three MBGs displaying different Ca, Si and P contents: the 29Si NMR spectra were recorded either directly by employing radio-frequency pulses to 29Si, or by magnetization transfers from neighbouring protons using cross polarization, thereby providing quantitative information about the silicate speciation present in the pore wall and at the MBG surface, respectively. The surface modifications were monitored for the three MBGs during their immersion in a simulated body fluid (SBF) for intervals between 30 min and one week. The results were formulated as a reaction sequence describing the interconversions between the distinct silicate species. We generally observed a depletion of Ca2+ ions at the MBG surface, and a minor condensation of the silicate-surface network over one week of SBF soaking.