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

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Search Results

Now showing 1 - 10 of 24

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.
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, Cedryck
In 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.
Targeting Agents in Biomaterial-Mediated Bone Regeneration
(International Journal of Molecular Sciences, 2023) Gisbert Garzarán, Miguel; Gómez Cerezo, María Natividad; Vallet Regí, María Dulce Nombre
Bone diseases are a global public concern that affect millions of people. Even though current treatments present high efficacy, they also show several side effects. In this sense, the development of biocompatible nanoparticles and macroscopic scaffolds has been shown to improve bone regeneration while diminishing side effects. In this review, we present a new trend in these materials, reporting several examples of materials that specifically recognize several agents of the bone microenvironment. Briefly, we provide a subtle introduction to the bone microenvironment. Then, the different targeting agents are exposed. Afterward, several examples of nanoparticles and scaffolds modified with these agents are shown. Finally, we provide some future perspectives and conclusions. Overall, this topic presents high potential to create promising translational strategies for the treatment of bone-related diseases. We expect this review to provide a comprehensive description of the incipient state-of-the-art of bone-targeting agents in bone regeneration.
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.
Multiscale porosity in mesoporous bioglass 3D-printed scaffolds for bone regeneration
(2021) Gómez Cerezo, María Natividad; Peña, Juan ; Ivanovski, Sašo ; Arcos Navarrete, Daniel; Vallet Regí, María Dulce Nombre; Vaquette, Cedryck
In 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 porosimetry and micro-computed tomography demonstrated that the PBS removal resulted in the formation of micropores 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.