Person: Vallet Regí, María Dulce Nombre
Loading...
First Name
María Dulce Nombre
Last Name
Vallet Regí
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Inorgánica
Identifiers
47 results
Search Results
Now showing 1 - 10 of 47
Item Effects of ipriflavone-loaded mesoporous nanospheres on the differentiation of endothelial cells and their modulation by macrophages.(Nanomaterials, 2021) Casarrubios Molina, Laura; Polo Montalvo, Alberto; Serrano, María Concepción; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaAngiogenic biomaterials for bone repair are being designed to promote vascularization and optimize tissue regeneration. The use of nanoparticles of bioactive materials loaded with different drugs represents an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. Ipriflavone (IP) prevents osteoporosis by inhibiting osteoclast activity and promoting preosteoblast differentiation into mature osteoblasts. Since endothelial progenitor cells (EPCs) are involved in the formation of blood vessels which are necessary for tissue regeneration, the isolation and characterization of porcine EPCs have been carried out in this work to evaluate the in vitro effects of unloaded (NanoMBGs) and IP-loaded nanospheres (NanoMBG-IPs) designed to stimulate osteogenesis. Because different signals between vascular and nonvascular cells are also essential to initiate angiogenic events, the potential modulating role of macrophages has been also evaluated by studying the expression of vascular endothelial growth factor receptor 2 (VEFGR2) as a specific marker for EPC differentiation under different culture conditions: a) EPCs in monoculture treated with NanoMBGs or NanoMBG-IPs, b) EPCs treated with conditioned media from basal, proinflammatory M1 and reparative M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, c) EPCs cocultured with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and d) EPCs cocultured with M2d angiogenic macrophages. Moreover, the endocytic mechanisms by which these nanospheres are incorporated by EPCs have been identified by using six endocytosis inhibitors (i.e. wortmannin, genistein, cytochalasin B, cytochalasin D, phenylarsine oxide and chlorpromazine) and before the addition of NanoMBGs labeled with fluorescein isothiocyanate. The results evidence the great potential of both NanoMBGs and NanoMBG-IPs to enhance VEFGR2 expression, directly related to angiogenesis, after intracellular incorporation by EPCs through different endocytic mechanisms including clathrin-dependent endocytosis, as the main entry mechanism, but also phagocytosis and caveolae-mediated uptake. The treatment of EPCs with culture media from basal, M1 and M2 macrophages and the development of cocultures of EPCs with macrophages in the absence and presence of these nanomaterials have also confirmed the maintenance of their angiogenic effect on EPCs even in the presence of phagocytic cells.Item Mesoporous bioactive glasses equipped with stimuli-responsive molecular gates for the controlled delivery of levofloxacin against bacteria(Chemistry-A european journal, 2018) Polo, Lorena; Gómez Cerezo, María Natividad; García-Fernández, Alba; Aznar, Elena; Vivancos, Jose Luis; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Martinez-Martinez, RamonIncrease of bone diseases incidence has boosted the study of ceramic biomaterials as a potential osteo-inductive scaffolds. Particularly, mesoporous bioactive glasses have demonstrated to possess a broad application in the bone regeneration field, due their osteo-regenerative capability and their ability to release drugs from its mesoporous structure. These special features have been studied as an option to fight against bone infection, which is one of the most common problems regarding bone regeneration therapies. In this work, we develop a mesoporous bioglass functionalized with polyamines and capped with ATP as molecular gate for the controlled release of the antibiotic levofloxacin. Phosphate bonds of the ATP are hydrolyzed in the presence of acid phosphatase (APase), which significantly increases its concentration in bone infection due to the activation of bone resorption processes. The solid has been characterized and tested successfully against bacteria. The final gated solid only induces bacterial death in the presence of acid phosphatase. Additionally, it has also been demonstrated that the solid is not toxic for human cells. The double function of the prepared nanodevice as drug delivery system and bone regeneration enhancer, confirms the possible development of a new approach in tissue engineering field, where controlled release of therapeutic agents can be finely tuned at the same time that osteoinduction is favored.Item Proton Environments in Biomimetic Calcium Phosphates Formed from Mesoporous Bioactive CaO-SiO2- P2O5 Glasses in vitro: Insights from Solid-State NMR(Journal of Physical Chemistry C, 2017) Mathew, Renny; Turdean-Ionescu, Claudia; Yu, Yang; Stevensson, Baltzar; Izquierdo Barba, Isabel; García Fontecha, Ana; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Eden, MattiasWhen exposed to body fluids, mesoporous bioactive glasses (MBGs) of the CaO{SiO2{P2O5 system develop a bone-bonding surface layer that initially consists of amorphous calcium phosphate(ACP), which transforms into hydroxy-carbonate apatite (HCA) with a very similar composition as bone/dentin mineral. Information from various 1H-based solid-state nuclear magnetic resonance (NMR) experiments were combined to elucidate the evolution of the proton speciations both at the MBG surface and within each ACP/HCA constituent of the biomimetic phosphate layer formed when each of three MBGs with distinct Ca, Si, and P contents was immersed in a simulated body fluid (SBF) for variable periods between 15 min and 30 days. Directly excited magic-angle-spinning (MAS) 1H NMR spectra mainly reflect the MBG component, whose surface is rich in water and silanol (SiOH) moieties. Double-quantum{single-quantum correlation 1H NMR experimentation at fast MAS revealed their interatomic proximities. The comparatively minor H species of each ACP and HCA component were probed selectively by heteronuclear 1H{31P NMR experimentation. The initially prevailing ACP phase comprises H2O and "non-apatitic" HPO2.Item Mesoporous bioactive glass/ɛ-polycaprolactone scaffolds promote bone regeneration in osteoporotic sheep(Acta Biomaterialia, 2019) Gómez Cerezo, María Natividad; Casarrubios Molina, Laura; Saiz-Pardo, M.; Ortega, L.; De Pablo, D.; Díaz-Güemes, I.; Fernández-Tomé, E.; Enciso, S; Sanchez-Margallo, F. M.; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreMacroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and ɛpolycaprolactone (PCL) have been prepared by robocasting. These scaffolds showed an excellent in vitro biocompatibility in contact with osteoblast like cells (Saos 2) and osteoclasts derived from RAW 264.7 macrophages. In vivo studies were carried out by implantation into cavitary defects drilled in osteoporotic sheep. The scaffolds evidenced excellent bone regeneration properties, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, thick trabeculae, high vascularization and high presence of osteoblasts and osteoclasts. In order to evaluate the effects of the local release of an antiosteoporotic drug, 1% (%wt) of zoledronic acid was incorporated to the scaffolds. The scaffolds loaded with zoledronic acid induced apoptosis in Saos 2 cells, impeded osteoclast differentiation in a time dependent manner and inhibited bone healing, promoting an intense inflammatory response in osteoporotic sheep.Item The relevance of biomaterials to the prevention and treatment of osteoporosis(Acta Biomaterialia, 2014) Arcos Navarrete, Daniel; Boccaccini, A. R.; Bohner, M.; Díez Pérez, A.; Epple, M.; Gómez Barrena, E.; Herrera, A.; Planell, J. A.; Rodríguez Manas, L.; Vallet Regí, María Dulce NombreOsteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. In order to analyze this scenario and propose alternatives to overcome it, the Spanish and European Network of Excellence for the Prevention and Treatment of Osteoporotic Fractures, ‘‘Ageing’’, was created. This network integrates three communities, e.g. clinicians, materials scientists and industrial advisors, tackling the same problem from three different points of view. Keeping in mind the premise ‘‘living longer, living better’’, this commentary is the result of the thoughts, proposals and conclusions obtained after one year working in the framework of this network.Item Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment.(Acta Biomaterialia, 2018) Izquierdo Barba, Isabel; Santos-Ruiz, L; Becerra, J; Feito Castellano, María José; Fernandez-Villa, D; Serrano, M.C; Diaz-Gúemes, I; Fernandez-Tome, B; Enciso, S; Sanchez-Margallo, F.M; Monopoli, D; Alfonso, H; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreThe osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone. STATEMENT OF SIGNIFICANCE Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with an osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.Item Molecular gates in mesoporous bioactive glasses for the treatment of bone tumors and infection(Acta Biomaterialia, 2016) Polo, Lorena; Gómez Cerezo, María Natividad; Vivancos, Jose Luis; Sancenón, Félix; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Martínez Máñez, RamónSilica mesoporous nanomaterials have been proved to have meaningful application in biotechnology and biomedicine. Particularly, mesoporous bioactive glasses are recently gaining importance thanks to their bone regenerative properties. Moreover, the mesoporous nature of these materials makes them suitable for drug delivery applications, opening new lines in the field of bone therapies. In this work, we have developed innovative nanodevices based on the implementation of adenosine triphosphate (ATP) and e-poly-l-lysine molecular gates using a mesoporous bioglass as an inorganic support. The systems have been previously proved to work properly with a fluorescence probe and subsequently with an antibiotic(levofloxacin) and an antitumoral drug(doxorubicin). The bioactivity of the prepared materials has also been tested, giving promising results. Finally, in vitro cell culture studies have been carried out; demonstrating that this gated devices can provide useful approaches for bone cancer and bone infection treatments. Statement of Significance Molecular-gated materials have recently been drawing attention due to their applications in fields as biomedicine and molecular recognition. For the first time as we are aware, we report herein a new enzymatic responsive molecular-gated device consisting in a mesoporous bioactive glass support implemented with two different molecular gates. Both controlled drug delivery properties and apatite-like phase formation ability of the device have been demonstrated, getting promising results. This approach opens up the possibility of developing new stimuli-responsive tailored biomaterials for bone cancer and infection treatments as well as regenerative bone grafts.Item Essential role of calcium phosphate heterogeneities in 2D-hexagonal and 3D-cubic SiO2-CaO-P2O5 mesoporous bioactive glasses(Chemistry of Materials, 2009) García, Ana; Cicuéndez Maroto, Mónica; Izquierdo Barba, Isabel; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreMesoporous bioactive glasses (MBGs) with a compoisition of 85SiO2-10CaO-5P2O5 (mol %) have been prepared through the evaporation-induced self-assembly (EISA) method, using P123 as a structure directing agent. For the first time, SiO2-CaO-P2O5 MBGs with identical composition and textural properties, but exhibiting different bicontinuous 3D-cubic and 2D-hexagonal structures, have been prepared. These materials allow us to discriminate the role of the structure on the bioactivity, from other parameters. To understand the role of each component on the mesostructure, local environment, and bioactive behavior, mesoporous 100SiO2, 95SiO2-5P2O5,and 90SiO2-10CaO (mol %) materials were also prepared under the same conditions. The results demonstrate that the joint presence of CaO and P2O5 results in amorphous calcium phosphate (ACP) clusters sited at the pore wall surface. This heterogeneity highly improves the bioactive behavior of these materials. In addition, the presence of ACP clusters within the silica network leads to different mesoporous structures. The mesoporous order can be tuned through a rigorous control of the solvent evaporation temperature during the mesophase formation, resulting in p6mm, p6mm/Ia3d coexistence, and Ia3d phases for 20, 30, and 40 C, respectively. Preliminary results indicate that, in the case of identical composition and textural properties, the mesoporous structure does not have influence on the apatite formation, although initial ionic exchange is slightly enhanced for 3D cubic bicontinuous structures.Item Multiscale porosity in mesoporous bioglass 3D-printed scaffolds for bone regeneration.(Materials Science & Engineering C, 2020) Gómez Cerezo, María Natividad; Peña López, Juan; Ivanovski, Saso; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Vaquette, CedryckIn order to increase the bone forming ability of MBG-PCL composite scaffold, microporosity was created in the struts of 3D-printed MBG-PCL scaffolds for the manufacturing of a construct with a multiscale porosity consisting of meso- micro- and macropores. 3D-printing imparted macroporosity while the microporosity was created by porogen removal from the struts, and the MBG particles were responsible for the mesoporosity. The scaffolds were 3D-printed using a mixture of PCL, MBG and phosphate buffered saline (PBS) particles, subsequently leached out. Microporous-PCL (pPCL) as a negative control, microporous MBG-PCL (pMBG-PCL) and non- microporous-MBG-PCL (MBG-PCL) were investigated. Scanning electron microscopy, mercury intrusion poros-imetry and micro-computed tomography demonstrated that the PBS removal resulted in the formation of mi-cropores inside the struts with porosity of around 30% for both pPCL and pMBG-PCL, with both constructs displaying an overall porosity of 8090%. In contrast, the MBG-PCL group had a microporosity of 6% and an overall porosity of 70%. Early mineralisation was found in the pMBG-PCL post-leaching out and this resulted in the formation a more homogeneous calcium phosphate layer when using a biomimetic mineralisation assay. Mechanical properties ranged from 5 to 25 MPa for microporous and non-microporous specimens, hence microporosity was the determining factor affecting compressive properties. MC3T3-E1 metabolic activity was increased in the pMBG-PCL along with an increased production of RUNX2. Therefore, the microporosity within a 3D-printed bioceramic composite construct may result in additional physical and biological benefits.Item Response of RAW 264.7 and J774A.1 macrophages to particles and nanoparticles of a mesoporous bioactive glass: A comparative study(Colloids and Surfaces B: Biointerfaces, 2021) Feito Castellano, María José; Casarrubios Molina, Laura; Oñaderra Sánchez, Mercedes; Gómez Duro, M.; Arribas, P.; Polo Montalvo, A.; Arcos Navarrete, Daniel; Portolés Pérez, María Teresa; Vallet Regí, María Dulce NombreMesoporous bioactive glasses (MBGs) are bioceramics designed to induce bone tissue regeneration and very useful materials with the ability to act as drug delivery systems. MBGs can be implanted in contact with bone tissue in different ways, as particulate material, in 3D scaffolds or as nanospheres. In this work, we assessed the effects of particles of mesoporous bioactive glass MBG-75S and mesoporous nanospheres NanoMBG-75S on RAW 264.7 and J774A.1 macrophages, which present different sensitivity and are considered as ideal models for the study of innate immune response. After evaluating several cellular parameters (morphology, size, complexity, proliferation, cell cycle and intracellular content of reactive oxygen species), the action MBG-75S particles and NanoMBG-75S on the polarization of these macrophages towards the pro-inflammatory (M1) or reparative (M2) phenotype was determined by the expression of specific M1 (CD80) and M2 (CD206, CD163) markers. We previously measured the adsorption of albumin and fibrinogen on MBG-75S particles and the production of pro-inflammatory cytokines as TNF-α and IL-6 by macrophages in response to these particles. This comparative study demonstrates that particles of mesoporous bioactive glass MBG-75S and mesoporous nanospheres NanoMBG-75S allow the appropriated development and function of RAW 264.7 and J774A.1 macrophages and do not induce polarization towards the M1 pro-inflammatory phenotype. Therefore, considering that these mesoporous biomaterials offer the possibility of loading drugs into their pores, the results obtained indicate their high potential for use as drug-delivery systems in bone repair and osteoporosis treatments without triggering an adverse inflammatory response.