A. Salinas - Academia.edu (original) (raw)
Papers by A. Salinas
Materials for Tissue Engineering
Handbook of Solid State Chemistry, 2017
Chapter 17. Mesoporous Bioactive Glasses in Tissue Engineering and Drug Delivery
Bioactive Glasses
Mesoporous glasses exhibit the quickest in vitro bioactive response observed to date for a synthe... more Mesoporous glasses exhibit the quickest in vitro bioactive response observed to date for a synthetic material. Furthermore, they present mesopore arrangements and very high surface areas and pore volumes. All these characteristics make them promising candidates as implants in the very near future. In this chapter, the state-of-the-art and the development of current research in mesoporous glasses as scaffolds in bone tissue engineering applications, and as matrixes in drug delivery systems, are reviewed.
Microporous and Mesoporous Materials, 2020
Mesoporous bioactive glasses, MBG, are gaining increasing interest in the design of new biomateri... more Mesoporous bioactive glasses, MBG, are gaining increasing interest in the design of new biomaterials for bone defects treatment. An important research trend to enhance their biological behavior is the inclusion of moderate amounts of oxides with therapeutical action such as CuO. In this paper, MBG with composition (85-x)SiO 2-10CaO-5P 2 O 5-xCuO (x = 0, 2.5% or 5 mol-%) were synthesized, investigating the influence of the CuO content and some synthesis parameters in their properties. Two batch were developed; first one using HCl as catalyst and chlorides as CaO and CuO precursors, second one, using HNO 3 and nitrates. MBG of chlorides batch exhibited calcium/copper phosphate nanoparticles, between 10 and 20 nm. Nevertheless, CuOcontaining MBG of nitrates batch showed nuclei of metallic copper nanoparticles larger than 50 nm and quicker in vitro bioactive responses. Thus, they were coated by an apatite-like layer after 24 h soaked in simulated body fluid, a remarkably short period for MBG containing up to 5 % of CuO. A model, focused in the copper location in the glass network, was proposed to relate nanostructure and in vitro behaviour. Moreover, after 24 h in MEM or THB culture media, all the MBG released therapeutic amounts of Ca 2+ and Cu 2+ ions. Because the quick bioactive response in SBF, the capacity to host biomolecules in their pores and to release therapeutic concentrations of Ca 2+ and Cu 2+ ions, MBG of the nitrate batch are considered as excellent biomaterials for bone regeneration.
Materials Today Bio
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Structure and solvation effects of PO43-, HPO42-, H2PO4− and H3PO4 from AM1 and PM3
Bioceramics, 1997
Solid State Ionics, 1997
Fine particles of aluminum oxide (amorphous, a, 3' and 0) have been synthesized by spray pyrolysi... more Fine particles of aluminum oxide (amorphous, a, 3' and 0) have been synthesized by spray pyrolysis as a function of both in situ and annealing temperatures and nature of precursors used in the preparation method. A scanning electron micrograph study shows as-received materials constituted by filled spherical particles, the ulterior annealing leading to the formation of small crystallites on the precursor spheres.
Amino−Polysiloxane Hybrid Materials for Bone Reconstruction
Chemistry of Materials, 2006
... H 1 - 0, 1, a H, only MPS and DAMO; C, contains calcium. Subindexes indicate the DAMO:MPS mol... more ... H 1 - 0, 1, a H, only MPS and DAMO; C, contains calcium. Subindexes indicate the DAMO:MPS molar ratio. ... Scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS) were carried out with a JEOL 6400 microscope coupled to a LINK AN 1000 device. ...
MRS Proceedings, 2004
ABSTRACTWe have prepared organic-inorganic hybrid materials (OIHM), incorporating an organic phas... more ABSTRACTWe have prepared organic-inorganic hybrid materials (OIHM), incorporating an organic phase in the inorganic precursor sol, using high power ultrasound for assistance with agitation. A sono-ormosil results after gelation. Colloidal silica particles have been added to these hybrids to enable network porous volume and pore radius to be tailored to specific requirements. Finally, in vitro bioactivity of this material has been promoted by adding calcium to the initial sol. The structure and bioactivity of these materials have been subjected to preliminary study, including their mechanical behaviour. These materials have a very fine structure especially after colloidal silica particles have been included. When immersed in a solution simulating blood plasma, they are bioactive, and the sample with colloid particles presents a better behaviour in vitro
SSRN Electronic Journal
Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also ... more Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also includes the development of new osteogenic and antibacterial biomaterials to treat the emergence of possible infection processes arising from surgery. This study evaluates the antibacterial properties of gelatin-coated meso-macroporous scaffolds based on the bioactive glass 80%SiO 2-15%CaO-5%P 2 O 5 (mol-%) before (BL-GE) and after being doped with 4% of ZnO (4ZN-GE) and loaded with both saturated and the minimal inhibitory concentrations of one of the antibiotics: levofloxacin (LEVO), vancomycin (VANCO), rifampicin (RIFAM) or gentamicin (GENTA). After physical-chemical characterization of materials, release studies of inorganic ions and antibiotics from the scaffolds were carried out. Moreover, molecular modelling allowed determining the electrostatic potential density maps and the hydrogen bonds of antibiotics and the glass matrix. Antibacterial in vitro studies (in planktonic, inhibition halos and biofilm destruction) with S. aureus and E. coli as bacteria models showed a synergistic effect of zinc ions and antibiotics. The effect was especially noticeable in planktonic cultures of S. aureus with 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and in E. coli cultures with LEVO or GENTA. Moreover, S. aureus biofilms were completely destroyed by 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and the E. coli biofilm total destruction was accomplished with 4ZN-GE scaffolds loaded with GENTA or LEVO. This approach could be an important step in the fight against microbial resistance and provide greatly needed options for bone infection treatment.
Journal of Non-Crystalline Solids
Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor ... more Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor (VEGF) from cells exposed to their biochemical influence, which plays a vital role in stimulating angiogenesis. Looking for this capacity, in this study three porous glasses were synthesized and characterized. Glass compositions (in mol-%) were: 60SiO2-(36-2x)CaO-4P2O5-xCuO-xSrO with x= 0, 1 or 2.5, respectively, for B60, CuSr-1 or CuSr-2.5 glasses. Cu 2+ and Sr 2+ ions were added because the reported biological capabilities of Cu 2+ as angiogenic stimulator and Sr 2+ as osteogenic stimulator. The objective of this study was to determine the concentration of the glass particles that, being out of the cytotoxic range, could increase VEGF secretion. The viability of cultivated bone marrow stromal cells (ST-2) was assessed. The samples were examined with light microscopy (LM) after the histochemical staining for haematoxylin and eosin (HE). The biological activity of glasses was evaluated in terms of the influence of the Cu 2+ and Sr 2+ ions on the cells. The dissolution products of CuSr-1 and CuSr-2.5 produced the highest secretion of VEGF from ST-2 cells after 48 h of incubation. The combination of Cu 2+ and Sr 2+ lays the foundation for engineering a bioactive glass than can lead to vascularized, functional bone tissue when used in bone regeneration applications.
Nanomaterials (Basel, Switzerland), Jan 4, 2018
Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their put... more Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their putative clinical use as scaffolds for bone regeneration. Their outstanding textural properties allow for high bioactivity when compared with other bioactive materials. Moreover, their great pore volumes allow these glasses to be loaded with a wide range of biomolecules to stimulate new bone formation. In this study, an MBG with a composition, in mol%, of 80% SiO₂⁻15% CaO⁻5% P₂O₅ (Blank, BL) was compared with two analogous glasses containing 4% and 5% of ZnO (4ZN and 5ZN) before and after impregnation with osteostatin, a C-terminal peptide from a parathyroid hormone-related protein (PTHrP). Zn ions were included in the glass for their bone growth stimulator properties, whereas osteostatin was added for its osteogenic properties. Glasses were characterized, and their cytocompatibility investigated, in pre-osteoblastic MC3T3-E1 cell cultures. The simultaneous additions of osteostatin and Zn i...
Current Pharmaceutical Design, 2015
The state of the art in the investigation of drugs release from Silica-based ordered Mesoporous M... more The state of the art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for each drug, are comprehensively listed. Next, the factors influencing the release of drugs from SMMs and the strategies used to control the drug delivery, specially the chemical functionalization of the silica surface, are discussed. In addition, how all these factors were gathered in a kinetic equation that describes the drug release from the mesoporous matrixes is explained. The new application of molecular modeling and docking in the investigation of the drug delivery mechanisms from SMMs is also presented. Finally, the new approaches under investigation in this field are mentioned including the design of smart stimuli-responsive materials and other recent proposals for a future investigation. .
Resumen Introducción: La proteína relacionada con la parthormona (PTHrP), un factor abundante en ... more Resumen Introducción: La proteína relacionada con la parthormona (PTHrP), un factor abundante en el tejido óseo, es un importante modulador de la formación ósea. Se ha demostrado que la PTHrP (107-111), conocida como osteostatina, cargada en el material cerámico mesoporoso SBA-15, ejerce acciones osteogénicas in vitro. Objetivo: Comprobar si dicho material y una versión funcionalizada del mismo (C8-SBA-15) promueven la reparación ósea en un modelo de defecto cavitario en el fémur del conejo. Material y métodos: Para ello se han llevado a cabo estudios histológicos e inmunohistoquímicos y de microtomografía computerizada (µCT). Resultados: Tras la implantación de los biomateriales no se observaron niveles significativos de inflamación ni resorción ósea (4 y 8 semanas). A las 8 semanas las biocerámicas no cargadas con la osteostatina se encontraban separadas de la médula ósea por una cápsula fibrosa, que disminuía de forma significativa en presencia del péptido. Se observó (por µCT) un aumento de la neo-formación ósea a diferentes distancias de los biomateriales, principalmente en los cargados con la osteostatina. Además, estos resultados fueron confirmados por inmunohistoquímica de marcadores osteoblásticos. Conclusión: Nuestros hallazgos sugieren que estas biocerámicas cargadas con la osteostatina son una buena estrategia para acelerar la regeneración ósea.
Phosphorus Research Bulletin, 1996
Eleven reaction stages are involved in bonding of living tissues to bioactive glasses; stage 4 is... more Eleven reaction stages are involved in bonding of living tissues to bioactive glasses; stage 4 is adsorption of Ca and P ions from solution, stage 5 is crystallization of hydroxy carbonate apatite. Molecular orbital models of H3PO4 hydrogen bonding shows that the AM-1 method matches experimental heats of formation.
Materials
In the search of a new biomaterial for the treatment of bone defects resulting from traumatic eve... more In the search of a new biomaterial for the treatment of bone defects resulting from traumatic events, an osteoporosis scenario with bone fractures, tumor removal, congenital pathologies or implant revisions for infection, we developed 3D scaffolds based on mesoporous bioactive glasses (MBGs) (85 − x)SiO2–5P2O5–10CaO–xSrO (x = 0, 2.5 and 5 mol.%). The scaffolds with meso-macroporosity were fabricated by pouring a suspension of MBG powders in polyvinyl alcohol (PVA) into a negative template of polylactic acid (PLA), followed by removal of the template by extraction at low temperature. SrO-containing MBGs exhibited excellent properties for bone substitution including ordered mesoporous structure, high textural properties, quick in vitro bioactive response in simulated body fluid (SBF) and the ability of releasing concentrations of strontium ions able to stimulate expression of early markers of osteoblastic differentiation. Moreover, the direct contact of MC3T3-E1 pre-osteoblastic cells...
Materials (Basel, Switzerland), Jan 2, 2018
Beneficial effects in bone cell growth and antibacterial action are currently attributed to Gaion... more Beneficial effects in bone cell growth and antibacterial action are currently attributed to Gaions. Thus, they can be used to upgrade mesoporous bioactive glasses (MBGs), investigated for tissue engineering, whenever they released therapeutic amounts of gallium ions to the surrounding medium. Three gallium-enriched MBGs with composition (in mol %)SiO₂-CaO-P₂O₅-5Ga₂O₃, being= 70,= 15,= 10 for;= 80,= 12,= 3 for; and= 80,= 15,= 0 for, were investigated and compared with the gallium-free 80SiO₂-15CaO-5P₂O₅ MBG ().Si andP MAS NMR analyses indicated that Gaacts as network modifier in the glass regions with higher polymerization degree and as network former in the zones with high concentration of classical modifiers (Caions).andexhibited a quick in vitro bioactive response because they were coated by an apatite-like layer after 1 and 3 days in simulated body fluid. Although we have not conducted biological tests in this paper (cells or bacteria),released high but non-cytotoxic amounts of G...
Bioengineering
This paper proposes a facile strategy for the zwitterionization of bioceramics that is based on t... more This paper proposes a facile strategy for the zwitterionization of bioceramics that is based on the direct incorporation of L-lysine amino acid via the ε-amino group onto mesoporous MCM-41 materials. Fourier transform infrared (FTIR) studies of lysine-grafted MCM-41 (MCM-LYS) simultaneously showed bands at 3080 and 1540 cm −1 and bands at 1625 and 1415 cm −1 corresponding to-NH 3+ /COO − pairs, which demonstrate the incorporation of the amino acid on the material surface keeping its zwitterionic character. Both elemental and thermogravimetric analyses showed that the amount of grafted lysine was 8 wt. % based on the bioceramic total weight. Moreover, MCM-LYS exhibited a reduction of adhesion of S. aureus and E. coli bacteria in 33% and 50%, respectively at physiological pH, as compared with pristine MCM-41. Biofilm studies onto surfaces showed that lysine functionalization elicited a reduction of the area covered by S. aureus biofilm from 42% to only 5% (88%). This research shows a simple and effective approach to chemically modify bioceramics using single amino acids that provides zwitterionic functionality, which is useful to develop new biomaterials that are able to resist bacterial adhesion.
European Journal of Pharmaceutical Sciences
Polypill is a medication designed for preventing heart attacks through a combination of drugs. Cu... more Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12.5/2.5/25/40 weight ratio. The procedure is based on Mesoporous Silica Nanoparticles (MSN) with MCM-41 structure (MSN-41) used as carrier, aimed to control release of the four drugs included in the polypill. In vitro release data were obtained by HPLC and the curves adjusted with a kinetic model. To explain the release results, a molecular model was built to determine the drug-matrix interactions, and quantum mechanical calculations were performed to obtain the electrostatic properties of each drug. Amlodipine, losartan and simvastatin were released from the polypill-MSN-41 system in a controlled way. This would be a favourable behaviour when used clinically because avoid too quick pressure decrease. However, the diuretic hydrochlorothiazide was quickly released from our system in the first minutes, as is needed in hypertensive urgencies. In addition, an increase in the stability of amlodipine and hydrochlorothiazide occurred in the polypill-MSN-41 system. Therefore, the new way of polypill dosage proposed can result in a safer and effective treatment.
Preparation, characterization, andin vitro release of Ibuprofen from Al2O3/PLA/PMMA composites
J Biomed Mater Res, 1998
Biomaterial comprising osteostatin for osseous regeneration and tissue engineering
Materials for Tissue Engineering
Handbook of Solid State Chemistry, 2017
Chapter 17. Mesoporous Bioactive Glasses in Tissue Engineering and Drug Delivery
Bioactive Glasses
Mesoporous glasses exhibit the quickest in vitro bioactive response observed to date for a synthe... more Mesoporous glasses exhibit the quickest in vitro bioactive response observed to date for a synthetic material. Furthermore, they present mesopore arrangements and very high surface areas and pore volumes. All these characteristics make them promising candidates as implants in the very near future. In this chapter, the state-of-the-art and the development of current research in mesoporous glasses as scaffolds in bone tissue engineering applications, and as matrixes in drug delivery systems, are reviewed.
Microporous and Mesoporous Materials, 2020
Mesoporous bioactive glasses, MBG, are gaining increasing interest in the design of new biomateri... more Mesoporous bioactive glasses, MBG, are gaining increasing interest in the design of new biomaterials for bone defects treatment. An important research trend to enhance their biological behavior is the inclusion of moderate amounts of oxides with therapeutical action such as CuO. In this paper, MBG with composition (85-x)SiO 2-10CaO-5P 2 O 5-xCuO (x = 0, 2.5% or 5 mol-%) were synthesized, investigating the influence of the CuO content and some synthesis parameters in their properties. Two batch were developed; first one using HCl as catalyst and chlorides as CaO and CuO precursors, second one, using HNO 3 and nitrates. MBG of chlorides batch exhibited calcium/copper phosphate nanoparticles, between 10 and 20 nm. Nevertheless, CuOcontaining MBG of nitrates batch showed nuclei of metallic copper nanoparticles larger than 50 nm and quicker in vitro bioactive responses. Thus, they were coated by an apatite-like layer after 24 h soaked in simulated body fluid, a remarkably short period for MBG containing up to 5 % of CuO. A model, focused in the copper location in the glass network, was proposed to relate nanostructure and in vitro behaviour. Moreover, after 24 h in MEM or THB culture media, all the MBG released therapeutic amounts of Ca 2+ and Cu 2+ ions. Because the quick bioactive response in SBF, the capacity to host biomolecules in their pores and to release therapeutic concentrations of Ca 2+ and Cu 2+ ions, MBG of the nitrate batch are considered as excellent biomaterials for bone regeneration.
Materials Today Bio
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Structure and solvation effects of PO43-, HPO42-, H2PO4− and H3PO4 from AM1 and PM3
Bioceramics, 1997
Solid State Ionics, 1997
Fine particles of aluminum oxide (amorphous, a, 3' and 0) have been synthesized by spray pyrolysi... more Fine particles of aluminum oxide (amorphous, a, 3' and 0) have been synthesized by spray pyrolysis as a function of both in situ and annealing temperatures and nature of precursors used in the preparation method. A scanning electron micrograph study shows as-received materials constituted by filled spherical particles, the ulterior annealing leading to the formation of small crystallites on the precursor spheres.
Amino−Polysiloxane Hybrid Materials for Bone Reconstruction
Chemistry of Materials, 2006
... H 1 - 0, 1, a H, only MPS and DAMO; C, contains calcium. Subindexes indicate the DAMO:MPS mol... more ... H 1 - 0, 1, a H, only MPS and DAMO; C, contains calcium. Subindexes indicate the DAMO:MPS molar ratio. ... Scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS) were carried out with a JEOL 6400 microscope coupled to a LINK AN 1000 device. ...
MRS Proceedings, 2004
ABSTRACTWe have prepared organic-inorganic hybrid materials (OIHM), incorporating an organic phas... more ABSTRACTWe have prepared organic-inorganic hybrid materials (OIHM), incorporating an organic phase in the inorganic precursor sol, using high power ultrasound for assistance with agitation. A sono-ormosil results after gelation. Colloidal silica particles have been added to these hybrids to enable network porous volume and pore radius to be tailored to specific requirements. Finally, in vitro bioactivity of this material has been promoted by adding calcium to the initial sol. The structure and bioactivity of these materials have been subjected to preliminary study, including their mechanical behaviour. These materials have a very fine structure especially after colloidal silica particles have been included. When immersed in a solution simulating blood plasma, they are bioactive, and the sample with colloid particles presents a better behaviour in vitro
SSRN Electronic Journal
Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also ... more Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also includes the development of new osteogenic and antibacterial biomaterials to treat the emergence of possible infection processes arising from surgery. This study evaluates the antibacterial properties of gelatin-coated meso-macroporous scaffolds based on the bioactive glass 80%SiO 2-15%CaO-5%P 2 O 5 (mol-%) before (BL-GE) and after being doped with 4% of ZnO (4ZN-GE) and loaded with both saturated and the minimal inhibitory concentrations of one of the antibiotics: levofloxacin (LEVO), vancomycin (VANCO), rifampicin (RIFAM) or gentamicin (GENTA). After physical-chemical characterization of materials, release studies of inorganic ions and antibiotics from the scaffolds were carried out. Moreover, molecular modelling allowed determining the electrostatic potential density maps and the hydrogen bonds of antibiotics and the glass matrix. Antibacterial in vitro studies (in planktonic, inhibition halos and biofilm destruction) with S. aureus and E. coli as bacteria models showed a synergistic effect of zinc ions and antibiotics. The effect was especially noticeable in planktonic cultures of S. aureus with 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and in E. coli cultures with LEVO or GENTA. Moreover, S. aureus biofilms were completely destroyed by 4ZN-GE scaffolds loaded with VANCO, LEVO or RIFAM and the E. coli biofilm total destruction was accomplished with 4ZN-GE scaffolds loaded with GENTA or LEVO. This approach could be an important step in the fight against microbial resistance and provide greatly needed options for bone infection treatment.
Journal of Non-Crystalline Solids
Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor ... more Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor (VEGF) from cells exposed to their biochemical influence, which plays a vital role in stimulating angiogenesis. Looking for this capacity, in this study three porous glasses were synthesized and characterized. Glass compositions (in mol-%) were: 60SiO2-(36-2x)CaO-4P2O5-xCuO-xSrO with x= 0, 1 or 2.5, respectively, for B60, CuSr-1 or CuSr-2.5 glasses. Cu 2+ and Sr 2+ ions were added because the reported biological capabilities of Cu 2+ as angiogenic stimulator and Sr 2+ as osteogenic stimulator. The objective of this study was to determine the concentration of the glass particles that, being out of the cytotoxic range, could increase VEGF secretion. The viability of cultivated bone marrow stromal cells (ST-2) was assessed. The samples were examined with light microscopy (LM) after the histochemical staining for haematoxylin and eosin (HE). The biological activity of glasses was evaluated in terms of the influence of the Cu 2+ and Sr 2+ ions on the cells. The dissolution products of CuSr-1 and CuSr-2.5 produced the highest secretion of VEGF from ST-2 cells after 48 h of incubation. The combination of Cu 2+ and Sr 2+ lays the foundation for engineering a bioactive glass than can lead to vascularized, functional bone tissue when used in bone regeneration applications.
Nanomaterials (Basel, Switzerland), Jan 4, 2018
Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their put... more Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their putative clinical use as scaffolds for bone regeneration. Their outstanding textural properties allow for high bioactivity when compared with other bioactive materials. Moreover, their great pore volumes allow these glasses to be loaded with a wide range of biomolecules to stimulate new bone formation. In this study, an MBG with a composition, in mol%, of 80% SiO₂⁻15% CaO⁻5% P₂O₅ (Blank, BL) was compared with two analogous glasses containing 4% and 5% of ZnO (4ZN and 5ZN) before and after impregnation with osteostatin, a C-terminal peptide from a parathyroid hormone-related protein (PTHrP). Zn ions were included in the glass for their bone growth stimulator properties, whereas osteostatin was added for its osteogenic properties. Glasses were characterized, and their cytocompatibility investigated, in pre-osteoblastic MC3T3-E1 cell cultures. The simultaneous additions of osteostatin and Zn i...
Current Pharmaceutical Design, 2015
The state of the art in the investigation of drugs release from Silica-based ordered Mesoporous M... more The state of the art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for each drug, are comprehensively listed. Next, the factors influencing the release of drugs from SMMs and the strategies used to control the drug delivery, specially the chemical functionalization of the silica surface, are discussed. In addition, how all these factors were gathered in a kinetic equation that describes the drug release from the mesoporous matrixes is explained. The new application of molecular modeling and docking in the investigation of the drug delivery mechanisms from SMMs is also presented. Finally, the new approaches under investigation in this field are mentioned including the design of smart stimuli-responsive materials and other recent proposals for a future investigation. .
Resumen Introducción: La proteína relacionada con la parthormona (PTHrP), un factor abundante en ... more Resumen Introducción: La proteína relacionada con la parthormona (PTHrP), un factor abundante en el tejido óseo, es un importante modulador de la formación ósea. Se ha demostrado que la PTHrP (107-111), conocida como osteostatina, cargada en el material cerámico mesoporoso SBA-15, ejerce acciones osteogénicas in vitro. Objetivo: Comprobar si dicho material y una versión funcionalizada del mismo (C8-SBA-15) promueven la reparación ósea en un modelo de defecto cavitario en el fémur del conejo. Material y métodos: Para ello se han llevado a cabo estudios histológicos e inmunohistoquímicos y de microtomografía computerizada (µCT). Resultados: Tras la implantación de los biomateriales no se observaron niveles significativos de inflamación ni resorción ósea (4 y 8 semanas). A las 8 semanas las biocerámicas no cargadas con la osteostatina se encontraban separadas de la médula ósea por una cápsula fibrosa, que disminuía de forma significativa en presencia del péptido. Se observó (por µCT) un aumento de la neo-formación ósea a diferentes distancias de los biomateriales, principalmente en los cargados con la osteostatina. Además, estos resultados fueron confirmados por inmunohistoquímica de marcadores osteoblásticos. Conclusión: Nuestros hallazgos sugieren que estas biocerámicas cargadas con la osteostatina son una buena estrategia para acelerar la regeneración ósea.
Phosphorus Research Bulletin, 1996
Eleven reaction stages are involved in bonding of living tissues to bioactive glasses; stage 4 is... more Eleven reaction stages are involved in bonding of living tissues to bioactive glasses; stage 4 is adsorption of Ca and P ions from solution, stage 5 is crystallization of hydroxy carbonate apatite. Molecular orbital models of H3PO4 hydrogen bonding shows that the AM-1 method matches experimental heats of formation.
Materials
In the search of a new biomaterial for the treatment of bone defects resulting from traumatic eve... more In the search of a new biomaterial for the treatment of bone defects resulting from traumatic events, an osteoporosis scenario with bone fractures, tumor removal, congenital pathologies or implant revisions for infection, we developed 3D scaffolds based on mesoporous bioactive glasses (MBGs) (85 − x)SiO2–5P2O5–10CaO–xSrO (x = 0, 2.5 and 5 mol.%). The scaffolds with meso-macroporosity were fabricated by pouring a suspension of MBG powders in polyvinyl alcohol (PVA) into a negative template of polylactic acid (PLA), followed by removal of the template by extraction at low temperature. SrO-containing MBGs exhibited excellent properties for bone substitution including ordered mesoporous structure, high textural properties, quick in vitro bioactive response in simulated body fluid (SBF) and the ability of releasing concentrations of strontium ions able to stimulate expression of early markers of osteoblastic differentiation. Moreover, the direct contact of MC3T3-E1 pre-osteoblastic cells...
Materials (Basel, Switzerland), Jan 2, 2018
Beneficial effects in bone cell growth and antibacterial action are currently attributed to Gaion... more Beneficial effects in bone cell growth and antibacterial action are currently attributed to Gaions. Thus, they can be used to upgrade mesoporous bioactive glasses (MBGs), investigated for tissue engineering, whenever they released therapeutic amounts of gallium ions to the surrounding medium. Three gallium-enriched MBGs with composition (in mol %)SiO₂-CaO-P₂O₅-5Ga₂O₃, being= 70,= 15,= 10 for;= 80,= 12,= 3 for; and= 80,= 15,= 0 for, were investigated and compared with the gallium-free 80SiO₂-15CaO-5P₂O₅ MBG ().Si andP MAS NMR analyses indicated that Gaacts as network modifier in the glass regions with higher polymerization degree and as network former in the zones with high concentration of classical modifiers (Caions).andexhibited a quick in vitro bioactive response because they were coated by an apatite-like layer after 1 and 3 days in simulated body fluid. Although we have not conducted biological tests in this paper (cells or bacteria),released high but non-cytotoxic amounts of G...
Bioengineering
This paper proposes a facile strategy for the zwitterionization of bioceramics that is based on t... more This paper proposes a facile strategy for the zwitterionization of bioceramics that is based on the direct incorporation of L-lysine amino acid via the ε-amino group onto mesoporous MCM-41 materials. Fourier transform infrared (FTIR) studies of lysine-grafted MCM-41 (MCM-LYS) simultaneously showed bands at 3080 and 1540 cm −1 and bands at 1625 and 1415 cm −1 corresponding to-NH 3+ /COO − pairs, which demonstrate the incorporation of the amino acid on the material surface keeping its zwitterionic character. Both elemental and thermogravimetric analyses showed that the amount of grafted lysine was 8 wt. % based on the bioceramic total weight. Moreover, MCM-LYS exhibited a reduction of adhesion of S. aureus and E. coli bacteria in 33% and 50%, respectively at physiological pH, as compared with pristine MCM-41. Biofilm studies onto surfaces showed that lysine functionalization elicited a reduction of the area covered by S. aureus biofilm from 42% to only 5% (88%). This research shows a simple and effective approach to chemically modify bioceramics using single amino acids that provides zwitterionic functionality, which is useful to develop new biomaterials that are able to resist bacterial adhesion.
European Journal of Pharmaceutical Sciences
Polypill is a medication designed for preventing heart attacks through a combination of drugs. Cu... more Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12.5/2.5/25/40 weight ratio. The procedure is based on Mesoporous Silica Nanoparticles (MSN) with MCM-41 structure (MSN-41) used as carrier, aimed to control release of the four drugs included in the polypill. In vitro release data were obtained by HPLC and the curves adjusted with a kinetic model. To explain the release results, a molecular model was built to determine the drug-matrix interactions, and quantum mechanical calculations were performed to obtain the electrostatic properties of each drug. Amlodipine, losartan and simvastatin were released from the polypill-MSN-41 system in a controlled way. This would be a favourable behaviour when used clinically because avoid too quick pressure decrease. However, the diuretic hydrochlorothiazide was quickly released from our system in the first minutes, as is needed in hypertensive urgencies. In addition, an increase in the stability of amlodipine and hydrochlorothiazide occurred in the polypill-MSN-41 system. Therefore, the new way of polypill dosage proposed can result in a safer and effective treatment.
Preparation, characterization, andin vitro release of Ibuprofen from Al2O3/PLA/PMMA composites
J Biomed Mater Res, 1998
Biomaterial comprising osteostatin for osseous regeneration and tissue engineering