Person:
Gómez Cerezo, María Natividad

First Name

María Natividad

Last Name

Gómez Cerezo

URI

https://hdl.handle.net/20.500.14352/86451

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Inorgánica

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 16

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, Ramon
Increase 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.
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 Nombre
Macroporous 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.
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, Ramón
Silica 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.
Vidrios mesoporosos bioactivos para el tratamiento de patologías óseas
(2019) Gómez Cerezo, María Natividad; Arcos Navarrete, Daniel
La presente tesis doctoral tiene como objetivo la obtención de vidrios mesoporosos bioactivos (MBGs) para ser utilizados en el tratamiento de defectos óseos asociados a patologías del tejido óseo. La motivación de este trabajo surge de la demanda de terapias regenerativas para el tratamiento de defectos óseos derivados de enfermedades como la osteoporosis, la infección o el cáncer. Generalmente la mayoría de los implantes óseos poseen una vida útil limitada y se implantan con fines sustitutivos. En la actualidad, relacionado en gran medida con el envejecimiento de la población, ha surgido la necesidad de diseñar materiales que favorezcan la regeneración ósea frente a los diseñados para su sustitución. En este sentido las biocerámicas bioactivas de tercera generación, en las que se engloban los MBGs presentan propiedades que favorecen la regeneración de defectos en el hueso promoviendo la restauración y reparación de los mismos. En la presente tesis hemos hemos abordado este objetivo siguiendo tres estrategias: 1. Optimización de las propiedades químicas y de la estructura porosa para determinar las composiciones químicas y propiedades texturales más adecuadas para los fines propuestos.2. Obtención de MBGs con capacidad regenerativa para tratamiento o prevención secundaria de tumores óseos e infecciones en el hueso.3. Obtención de andamios macroporosos de MBGs para regeneración de hueso en pacientes osteoporóticos...
The response of pre-osteoblasts and osteoclasts to gallium containing mesoporous bioactive glasses.
(Acta Biomaterialia, 2018) Gómez Cerezo, María Natividad; Verron, E; Montouillout, V; Fayon, F; Lagadec, P; Bouler, J.M.; Bujoli, B; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre
Mesoporous bioactive glasses (MBGs) in the system SiO2-CaO-P2O5-Ga2O3 have been synthesized by the evaporation induced self-assembly method and subsequent impregnation with Ga cations. Two different compositions have been prepared and the local environment of Ga(III) has been characterized using 29Si, 71Ga and 31P NMR analysis, demonstrating that Ga(III) is efficiently incorporated as both, network former (GaO4 units) and network modifier (GaO6 units). In vitro bioactivity tests evidenced that Ga-containing MBGs retain their capability for nucleation and growth of an apatite-like layer in contact with a simulated body fluid with ion concentrations nearly equal to those of human blood plasma. Finally, in vitro cell culture tests evidenced that Ga incorporation results in a selective effect on osteoblasts and osteoclasts. Indeed, the presence of this element enhances the early differentiation towards osteoblast phenotype while disturbing osteoclastogenesis. Considering these results, Ga-doped MBGs might be proposed as bone substitutes, especially in osteoporosis scenarios.
Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep.
(Acta Biomaterialia, 2019) Casarrubios Molina, Laura; Gómez Cerezo, María Natividad; Sánchez Salcedo, Sandra; Feito Castellano, María José; Serrano, M.C.; Saiz-Pardo, M.; Ortega Menor, Lorena; De Pablo, D.; Díaz-Güemes, I.; Fernández-Tomé, E.; Enciso, S; Portolés Pérez, María Teresa; Sanchez-Margallo, F.M; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Sanchez-Margallo, F. M.
Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and forested osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis.
Tailoring the biological response of mesoporous bioactive materials
(Journal of Materials Chemistry B, 2015) Gómez Cerezo, María Natividad; Izquierdo Barba, Isabel; Arcos, Daniel; Vallet Regí, María Dulce Nombre
Mesoporous bioactive glasses (MBGs) in the SiO2–CaO–P2O5 system have been prepared using different non-ionic structure directing agents (SDA): Brij58, F68, P123 and F127. For the first time, the bioactive response of MBGs can be tailored with the kind of SDA incorporated. This is because, in addition to the textural properties, we can use the SDA to tailor the local atomic environment within the MBG struts. These features lead to differences in the in vitro bioactive behaviour of MBGs. Among the different SDAs used in this work, the triblock copolymer F68 leads to MBGs that exhibit the fastest bioactivity and the fastest differentiation induction from a pre-osteoblast to an osteoblast phenotype. These results are explained in terms of a highly ordered mesoporous structure, more free calcium cations acting as silica network modifiers and small mesopores that avoid the formation of CaP nuclei within pores, which could obstruct the ionic exchange with the surrounding fluids.
Molecular gates in mesoporous bioactive glasses for the treatment of bone tumors and infection
(Acta Biomaterialia, 2017) Polo, Lorena ; Gómez Cerezo, María Natividad; Aznar, Elena ; Vivancos, José-Luis ; Sancenón, Félix ; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Martínez-Máñez, Ramón
Silica 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 ε-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.
Mesoporous bioactive glass/ɛ-polycaprolactone scaffolds promote bone regeneration in osteoporotic sheep
(2019) Gómez Cerezo, María Natividad; Casarrubios Molina, Laura; Saiz-Pardo, M. ; Ortega, L. ; Pablo, D. De ; Díaz-Güemes, I. ; Fernández-Tomé, B. ; Enciso, S. ; Sánchez-Margallo, F.M. ; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre
Macroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and ɛ-polycaprolactone (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. STATEMENT OF SIGNIFICANCE: In addition to an increase in bone fragility and susceptibility to fracture, osteoporosis also hinders the clinical success of endosseous implants and grafting materials for the treatment of bone defects. For the first time, macroporous scaffolds made of mesoporous bioactive glass and ε-caprolactone have been evaluated in a sheep model that mimics the osteoporosis conditions in humans. These implants fostered bone regeneration, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, showing thick trabeculae and a high vascularization degree. Our results indicate that macroporous structures containing highly bioactive mesoporous glasses could be excellent candidates for the regenerative treatment of bone defects in osteoporotic patients.
Tailoring the biological response of mesoporous bioactive materials
(Journal of Materials Chemistry B, 2013) Gómez Cerezo, María Natividad; Izquierdo Barba, Isabel; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre
Silica 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 ε-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.