Person: Gómez Cerezo, María Natividad
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First Name
María Natividad
Last Name
Gómez Cerezo
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Inorgánica
Identifiers
8 results
Search Results
Now showing 1 - 8 of 8
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 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.Item 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 NombreMacroporous 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.Item Incorporation and effects of mesoporous SiO2-CaO nanospheres loaded with ipriflavone on osteoblast/osteoclast cocultures(European Journal of Pharmaceutics and Biopharmaceutics, 2018) Casarrubios Molina, Laura; Gómez Cerezo, María Natividad; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaMesoporous nanospheres in the system SiO2-CaO (NanoMBGs) with a hollow core surrounded by a radial arrangement of mesopores were characterized, labeled with FITC (FITC-NanoMBGs) and loaded with ipriflavone (NanoMBG-IPs) in order to evaluate their incorporation and their effects on both osteoblasts and osteoclasts simultaneously and maintaining the communication with each other in coculture. The influence of these nanospheres on macrophage polarization towards pro-inflammatory M1 or reparative M2 phenotypes was also evaluated in basal and stimulated conditions through the expression of CD80 (as M1 marker) and CD206 (as M2 marker) by flow cytometry and confocal microscopy. NanoMBGs did not induce the macrophage polarization towards the M1 pro-inflammatory phenotype, favoring the M2 reparative phenotype and increasing the macrophage response capability against stimuli as LPS and IL-4. NanoMBG-IPs induced a significant decrease of osteoclast proliferat ion and resorption activity after 7 days in coculture with osteoblasts, without affecting osteoblast proliferation and viability. Drug release test demonstrated that only a fraction of the payload is released by diffusion, whereas the rest of the drug remains within the hollow core after 7 days, thus ensuring the local long-term pharmacological treatment beyond the initial fast IP release. All these data ensure an appropriate immune response to these nanospheres and the potential application of NanoMBG-IPs as local drug delivery system in osteoporotic patients.Item Injectable mesoporous bioactive nanoparticles regenerate bone tissue under osteoporosis conditions(Acta Biomaterialia, 2022) Arcos Navarrete, Daniel; Gómez Cerezo, María Natividad; Saiz-Pardo Sanz, Melchor; Pablo Velasco, David de; Ortega Medina, Luis; Enciso, Silvia; Fernández Tomé, Blanca; Díaz Güemes, Idoia; Sánchez Margallo, Francisco Miguel; Casarrubios Palomar, Luis; Feito Castellano, María José; Portolés Pérez, María Teresa; Vallet Regí, María Dulce NombreThe osteogenic capability of mesoporous bioactive nanoparticles (MBNPs) in the SiO2–CaO system has been assessed in vivo using an osteoporotic rabbit model. MBNPs have been prepared using a double template method, resulting in spherical nanoparticles with a porous core-shell structure that has a high surface area and the ability to incorporate the anti-osteoporotic drug ipriflavone. In vitro expression of the pro-inflammatory genes NF-κB1, IL-6, TNF-α, P38 and NOS2 in RAW-264.7 macrophages, indicates that these nanoparticles do not show adverse inflammatory effects. An injectable system has been prepared by suspending MBNPs in a hyaluronic acid-based hydrogel, which has been injected intraosseously into cavitary bone defects in osteoporotic rabbits. The histological analyses evidenced that MBNPs promote bone regeneration with a moderate inflammatory response. The incorporation of ipriflavone into these nanoparticles resulted in a higher presence of osteoblasts and enhanced angiogenesis at the defect site, but without showing significant differences in terms of new bone formation.Item Effects of a mesoporous bioactive glass on osteoblasts, osteoclasts and macrophages(Journal of Colloid and Interface Science, 2018) Gómez Cerezo, María Natividad; Casarrubios Molina, Laura; Morales, I.; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaA 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.Item Ipriflavone-loaded mesoporous nanospheres with potential applications for periodontal treatment.(Nanomaterials, 2020) Casarrubios Molina, Laura; Gómez Cerezo, María Natividad; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaThe incorporation and effects of hollow mesoporous nanospheres in the systemSiO2–CaO (nanoMBGs) containing ipriflavone (IP), a synthetic isoflavone that prevents osteoporosis, were evaluated. Due to their superior porosity and capability to host drugs, these nanoparticles are designed as a potential alternative to conventional bioactive glasses for the treatment of periodontal defects. To identify the endocytic mechanisms by which these nanospheres are incorporated within the MC3T3-E1 cells, five inhibitors (cytochalasin B, cytochalasin D, chlorpromazine, genistein and wortmannin) were used before the addition of these nanoparticles labeled with fluorescein isothiocyanate (FITC–nanoMBGs). The results indicate that nanoMBGs enter the pre-osteoblasts mainly through clathrin-dependent mechanisms and in a lower proportion by macropinocytosis. The present study evidences the active incorporation of nanoMBG–IPs by MC3T3-E1 osteoprogenitor cells that stimulate their differentiation into mature osteoblast phenotype with increased alkaline phosphatase activity. The final aim of this study is to demonstrate the biocompatibility and osteogenic behavior of IP-loaded bioactive nanoparticles to be used for periodontal augmentation purposes and to shed light on internalization mechanisms that determine the incorporation of these nanoparticles into the cells.Item Mesoporous bioactive glass/epsilon-polycaprolactone scaffolds promote bone regeneration in osteoporotic sheep(Acta Biomaterialia, 2019) Gómez Cerezo, María Natividad; Casarrubios Molina, Laura; Saiz-Pardo Sanz, Melchor; Ortega, Luis; de Pablo, David; Díaz-Güemes, Idoia; Fernández-Tomé, Blanca; Enciso, Sivlia; Sánchez-Margallo, Francisco Miguel; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Vallet Regí, María Dulce NombreMacroporous scaffolds made of a SiO2-CaO-P2O5 mesoporous bioactive glass (MBG) and epolycaprolactone (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.