Effects of 3D nanocomposite bioceramic scaffolds on the immune response

The interaction of new nanocomposite mesoporous glass/hydroxyapatite (MGHA) scaffolds with immune cells involved in both innate and acquired immunity has been studied in vitro as an essential aspect of their biocompatibility assessment. Since the immune response can be affected by the degradation products of bioresorbable scaffolds and scaffold surface changes, both processes have been evaluated. No alterations in proliferation and viability of RAW-264.7 macrophage-like cells were detected after culture on MGHA scaffolds which did not induce cell apoptosis. However, a slight cell size decrease and an intracellular calcium content increase were observed after contact of this cell line with MGHA scaffolds or their extracts. Although no changes in the percentages of RAW cells with low and high contents of reactive oxygen species (ROS) are observed by the treatment with 7 day extracts, this study has revealed modifications of these percentages after direct contact with scaffolds and by the treatment with 24 h extracts, related to the high reactivity/bioactivity of this MGHA nanocomposite at initial times. Furthermore, when normal fresh murine spleen cells were used as an experimental model closer to physiological conditions, no significant alterations in the activation of different immune cell subpopulations were detected in the presence of 24 h MGHA extract. MGHA scaffolds did not affect either the spontaneous apoptosis or intracellular cytokine expression (IL-2, IL-10, IFN-gamma, and TNF-alpha.) after 24 h treatment. The results obtained in the present study with murine immune cell subpopulations (macrophages, lymphocytes B, lymphocytes T and natural killer cells) support the biocompatibility of the MGHA material and suggest an adequate host tissue response to their scaffolds upon their implantation

Metabolomic response of osteosarcoma cells to nanographene oxide-mediated hyperthermia.

Nanographene oxide (nGO)-mediated hyperthermia has been increasingly investigated as a localized, minimally invasive anticancer therapeutic approach. Near InfraRed (NIR) light irradiation for inducing hyperthermia is particularly attractive, because biological systems mostly lack chromophores that absorb in this spectral window, facilitating the selective heating and destruction of cells which have internalized the NIR absorbing- nanomaterials. However, little is known about biological effects accompanying nGO-mediated hyperthermia at cellular and molecular levels. In this work, well-characterized pegylated nGO sheets with a hydrodynamic size of 300 nm were incubated with human Saos-2 osteosarcoma cells for 24 h and their internalization verified by flow cytometry and confocal microscopy. No effect on cell viability was observed after nGO uptake by Saos-2 cells. However, a proliferation delay was observed due to the presence of nGO sheets in the cytoplasm. 1H NMR metabolomics was employed to screen for changes in the metabolic profile of cells, as this could help to improve understanding of cellular responses to nanomaterials and provide new endpoint markers of effect. Cells inter- nalizing nGO sheets showed noticeable changes in several metabolites compared to control cells, including decreased levels of several amino acids, taurine and creatine and increased levels of phosphocholine and ur- idine/adenosine nucleotides. After NIR irradiation, cells showed decreases in glutamate and uridine nucleotides, together with increases in glycerophosphocholine and adenosine monophosphate. Overall, this study has shown that the cellular metabolome sensitively responded to nGO exposure and nGO-mediated hyperthermia and that NMR metabolomics is a powerful tool to investigate treatment responses

Effects of a mesoporous bioactive glass on osteoblasts, osteoclasts and macrophages

A mesoporous bioactive glass (MBG) of molar composition 75SiO2-20CaO-5P2O5 (MBG-75S) has been synthetized as a potential bioceramic for bone regeneration purposes. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption studies and transmission electron microscopy (TEM) demonstrated that MBG-75S possess a highly ordered mesoporous structure with high surface area and porosity, which would explain the high ionic exchange rate (mainly calcium and silicon soluble species) with the surrounded media. MBG-75S showed high biocompatibility in contact with Saos-2 osteoblast-like cells. Concentrations up to 1 mg/ml did not lead to significant alterations on either morphology or cell cycle. Regarding the effects on osteoclasts, MBG-75S allowed the differentiation of RAW264.7 macrophages into osteoclast-like cells but exhibiting a decreased resorptive activity. These results point out that MBG-75S does not inhibit osteoclastogenesis but reduces the osteoclast bone-resorbing capability. Finally, in vitro studies focused on the innate immune response, evidenced that MBG-75S allows the proliferation of macrophages without inducing their polarization towards the M1 pro-inflammatory phenotype. This in vitro behavior is indicative that MBG-75S would just induce the required innate immune response without further inflammatory complications under in vivo conditions. The overall behavior respect to osteoblasts, osteoclasts and macrophages, makes this MBG a very interesting candidate for bone grafting applications in osteoporotic patients

Herramientas de comunicación en el aprendizaje de la Bioquímica

Sección Deptal. de Bioquímica y Biología Molecular (Biológicas)Depto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasFac. de Ciencias QuímicasFALSEsubmitte

Nanocrystalline silicon substituted hydroxyapatite effects on osteoclast differentiation and resorptive activity

In the present study, the effects of nanocrystalline hydroxyapatite (nano-HA) and nanocrystalline Si-substituted hydroxyapatite (nano-SiHA) on osteoclast differentiation and resorptive activity have been evaluated in vitro using osteoclast-like cells. The action of these materials on proinflammatory and reparative macrophage populations was also studied. Nano-SiHA disks delayed the osteoclast differentiation and decreased the resorptive activity of these cells on their surface, as compared to nano-HA samples, without affecting cell viability. Powdered nano-SiHA also induced an increase of the reparative macrophage population. These results along with the beneficial effects on osteoblasts previously observed with powdered nano-SiHA suggest the potential of this biomaterial for modulating the fundamental processes of bone formation and turnover, preventing bone resorption and enhancing bone formation at implantation sites in treatment of osteoporotic bone and in bone repair and regeneration

Nanocrystalline silicon substituted hydroxyapatite effects on osteoclast differentiation and resorptive activity

In the present study, the effects of nanocrystalline hydroxyapatite (nano-HA) and nanocrystalline Si-substituted hydroxyapatite (nano-SiHA) on osteoclast differentiation and resorptive activity have been evaluated in vitro using osteoclast-like cells. The action of these materials on proinflammatory and reparative macrophage populations was also studied. Nano-SiHA disks delayed the osteoclast differentiation and decreased the resorptive activity of these cells on their surface, as compared to nano-HA samples, without affecting cell viability. Powdered nano-SiHA also induced an increase of the reparative macrophage population. These results along with the beneficial effects on osteoblasts previously observed with powdered nano-SiHA suggest the potential of this biomaterial for modulating the fundamental processes of bone formation and turnover, preventing bone resorption and enhancing bone formation at implantation sites in treatment of osteoporotic bone and in bone repair and regeneration

Effects of immobilized VEGF on endothelial progenitor cells cultured on silicon substituted and nanocrystalline hydroxyapatites

Vascular endothelial growth factor (VEGF) plays an essential role in angiogenesis and vascular homeostasis. Endothelial progenitor cells (EPCs) are primitive bone marrow cells participating in neovascularization and revascularization processes, which also promote bone regeneration. Synthetic hydroxyapatite (HA) has been widely used in bone repair and implant coatings. In HA-based materials, small levels of ionic substitution by silicon (Si) have significant effects on osteoclastic and osteoblastic responses. Moreover, nanocrystalline hydroxyapatites (nano-HA) display enhanced bioreactivity and beneficial effects in bone formation. In this work, the angiogenic potential of VEGF-121 adsorbed on crystalline and nanocrystalline HAs with different Si proportion is evaluated with endothelial-like cells derived from EPCs cultured on nano-HA, nano-SiHA0.25, nano-SiHA0.4, HA, SiHA0.25 and SiHA0.4 disks. The Si amount incorporated for x ¼ 0.25 is enough to yield changes in the textural parameters and surface charge without decomposing the HA phase. Si substitution for x ¼ 0.4 does not result in pure Si-substituted apatites. Si probably remains at the grain boundaries as amorphous silica in nano-SiHA0.4 and SiHA0.4 is decomposed in a-TCP and HA after 1150 �C treatment. Immobilized VEGF on nano-HA, nano-SiHA0.25, nano-SiHA0.4, HA, SiHA0.25 and SiHA0.4 maintains its function exerting a local regulation of the cell response. The crystallite size and topography of nanocrystalline HAs could produce insufficient and weak contacts with endothelial-like cells triggering anoikis. Concerning Si proportion, the best results are obtained with SiHA0.25/VEGF and nano- SiHA0.25/VEGF disks. All these results suggest the potential utility of SiHA0.25/VEGF and nano-SiHA0.25/VEGF for bone repair and tissue engineering by promoting angiogenesis

Entrevista a Victoria Sau Sánchez: profesora de Psicología en la Universidad de Barcelona, historiadora e histórica activista feminista catalana (Barcelona, 1/04/1930 -6/11/2013)

[Resumen] Entrevista a Victoria Sau Sánchez. Esta entrevista fue realizada por Carmen Magallón Portolés y María José Barral Morán, en julio de 2009, en el domicilio particular de Victoria Sau, en Barcelona, y formaba parte de las entrevistas realizadas a 9 científicas españolas de éxito en el seno de un proyecto de investigación titulado: “Científicas que dejan huella: interacciones entre experiencia vital y contribución a la ciencia”.Ministerio de Educación y Ciencia; CSO2008-05121-E/SOCIUniversidad de Zaragoza; UZ2008-BIO-0

Effects of Human and Porcine Adipose Extracellular Matrices Decellularized by Enzymatic or Chemical Methods on Macrophage Polarization and Immunocompetence

The decellularized extracellular matrix (ECM) obtained from human and porcine adipose tissue (AT) is currently used to prepare regenerative medicine bio-scaffolds. However, the influence of these natural biomaterials on host immune response is not yet deeply understood. Since macrophages play a key role in the inflammation/healing processes due to their high functional plasticity between M1 and M2 phenotypes, the evaluation of their response to decellularized ECM is mandatory. It is also necessary to analyze the immunocompetence of macrophages after contact with decellularized ECM materials to assess their functional role in a possible infection scenario. In this work, we studied the effect of four decellularized adipose matrices (DAMs) obtained from human and porcine AT by enzymatic or chemical methods on macrophage phenotypes and fungal phagocytosis. First, a thorough biochemical characterization of these biomaterials by quantification of remnant DNA, lipids, and proteins was performed, thus indicating the efficiency and reliability of both methods. The proteomic analysis evidenced that some proteins are differentially preserved depending on both the AT origin and the decellularization method employed. After exposure to the four DAMs, specific markers of M1 proinflammatory and M2 anti-inflammatory macrophages were analyzed. Porcine DAMs favor the M2 phenotype, independently of the decellularization method employed. Finally, a sensitive fungal phagocytosis assay allowed us to relate the macrophage phagocytosis capability with specific proteins differentially preserved in certain DAMs. The results obtained in this study highlight the close relationship between the ECM biochemical composition and the macrophage’s functional role.This work has been supported by the European Union’s Horizon 2020 Research and Innovation Programme (H2020-FETOPEN-2018-2020, NeuroStimSpinal Project, Grant Agreement No. 829060). M.C. acknowledges the European Union0s Horizon 2020 Research and Innovation Programme for her contract under the NeuroStimSpinal Project. LC is grateful to the Universidad Complutense de Madrid for an UCM fellowship

Life Paths of Successful Women Scientists in Spain

This article discusses interactions between the life paths of women scientists and their status and contributions to science. It is a qualitative study which highlights factors that influenced the successful career of nine Spanish women scientists. These factors include the family encouragement, the novelty of the scientific field or branch in which they work, the mentors they had along their career and the periods of time spent abroad. The women scientist included in the sample are working in different fields: Physics, Psychology, and Neurobiology. The analysis of their professional paths reveals that to develop a successful scientific career, the organization of daily, domestic and private life is important, as well as the existence of other social opportunities which are outlined in the article