Person:
Jiménez Holguín, Javier

First Name

Javier

Last Name

Jiménez Holguín

URI

https://hdl.handle.net/20.500.14352/86241

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Identifiers

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Now showing 1 - 9 of 9

Cu-doped hollow bioactive glass nanoparticles for bone infec-tion treatment
(Pharmaceutics, 2022) Jiménez Holguín, Javier; Sánchez Salcedo, Sandra; Cicuéndez Maroto, Mónica; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.
In search of new approaches to treat bone infection and prevent drug resistance development, a nanosystem based on hollow bioactive glass nanoparticles (HBGN) of composition 79.5SiO2–(18-x)CaO–2.5P2O5–xCuO (x = 0, 2.5 or 5 mol-% CuO) was developed. The objective of the study was to evaluate the capacity of the HBGN to be used as nanocarriers of the broad-spectrum anti-biotic danofloxacin and source of bactericidal Cu2+ ions. Core-shell nanoparticles with specific surface areas close to 800 m2/g and pore volumes around 1 cm3/g were obtained by using hexa-decyltrimethylammonium bromide (CTAB) and poly (styrene)-block-poly (acrylic acid) (PS-b-PAA) as structure-directing agents. Flow cytometry studies showed the cytocompatibility of the nanoparticles in MC3T3-E1 pre-osteoblastic cell cultures. Ion release studies confirmed the release of non-cytotoxic concentrations of Cu2+ ions within the therapeutic range. Moreover, it was shown that the inclusion of copper in the system resulted in a more gradual release of da-nofloxacin that was extended over one week. The bactericidal activity of the nanosystem was evaluated with E. coli and S. aureus strains. Nanoparticles with copper were not able to reduce bacterial viability by themselves and Cu-free HBGN failed to reduce bacterial growth, despite releasing higher antibiotic concentrations. However, HBGN enriched with copper and da-nofloxacin drastically reduced bacterial growth in sessile, planktonic and biofilm states, which was attributed to a synergistic effect between the action of Cu2+ ions and danofloxacin. There-fore, the nanosystem here investigated is a promising candidate as an alternative for the local treatment of bone infections.
Multifunctional antibiotic- and zinc-containing mesoporous bioactive glass scaffolds to fight bone infection.
(Acta Biomaterialia, 2020) Heras, Clara; Jiménez Holguín, Javier; Doadrio Villarejo, Antonio Luis; Vallet Regí, María Dulce Nombre; Sánchez Salcedo, Sandra; Salinas Sánchez, Antonio J.
Bone regeneration is a clinical challenge which requires multiple approaches. Sometimes, it also includes the development of 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%SiO2–15%CaO–5%P2O5 (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 needed options for bone infection treatment.
In vivo behavior in rabbit radius bone defect of scaffolds based on nanocarbonate hydroxyapatite
(Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2024) García Lamas, Lorena; Peña López, Juan; Román Zaragoza, Jesús; Cabañas Criado, María Victoria; Bravo Giménez, Beatriz; Jiménez Díaz, Verónica; Sánchez Salcedo, Sandra; Jiménez Holguín, Javier; Abella, Mónica; Desco, Manuel; Lozano Borregón, Daniel; Cecilia López, David; Salinas Sánchez, Antonio Jesús
Bone defects treatment may require the use of biomaterials that behave as a support and promote bone regeneration. Limitations associated with the use of autografts and allografts make it necessary to design new synthetic bone substitutes. Some of the most promising biomaterials currently under investigation are based on nanocarbonate hydroxyapatite (nCHA). In this study, we studied the bone-inducing capacity of nCHA-based scaffolds alone (SAG) and enriched with osteostatin (SAGO) or with bone marrow aspirate(SAGB) after implantation for 12 weeks in a 15-mm long critical defect performed in the radius of New Zealand rabbits. Bone formation obtained was compared with a group with the unfilled defect (CE), as control group, and other with the defect filed with iliac crest autograft (GS), as gold standard. X-ray follow-up was performed at 2, 4, 6 and 12 weeks and μCT and histological studies at 12 weeks. The radiological results showed a greater increment in bone formation in the GS group (75%–100%), followed by the SAG and SAGB groups (50%–75%). μCT results showed an increase of bone volume/tissue volume values in GS group followed by SAG and SAGB groups (0.53, 0.40, and 0.31 respectively) compared with CE group (0.26). Histological results showed limited resorption of the nCHA scaffolds and partial osseointegration in the SAG and SAGB groups. However, in the SAGO group, the presence of connective tissue encapsulating the scaffold was detected. In SAG, SAGB, and increase of bone formation were observed compared with CE group, but less than the GS group. Thus, the investigated materials represent a significant advance in the design of synthetic materials for bone grafting, but further studies are needed to bring their in vivo behavior closer to autograft, the gold standard.
Development and evaluation of copper-containing mesoporous bioactive glasses for bone defects therapy.
(Microporous and Mesoporous Materials, 2020) Jiménez Holguín, Javier; Sánchez Salcedo, Sandra; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.
Mesoporous bioactive glasses (MBGs) 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. MBGs with composition (85-x)SiO2–10- CaO–5P2O5–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 series were developed; first one used HCl as catalyst and chlorides as CaO and CuO precursors, second one, used HNO3 and nitrates. MBGs of chlorides family exhibited calcium/copper phosphate nanoparticles between 10 and 20 nm in size. Nevertheless, CuO-containing MBGs of nitrates family showed metallic copper nanoparticles larger than 50 nm as well as quicker in vitro bioactive responses. Thus, MBGs of the nitrate series were coated by an apatite-like layer after 24 h soaked in simulated body fluid (SBF) a remarkably short period for a MBG containing 5% of CuO. A model, focused in the location of copper in the glass network, was proposed to relate nanostructure and in vitro behaviour. Moreover, after 24 h soaked in MEM or THB culture media, all the MBGs released therapeutic amounts of Ca2+ and Cu2+ ions. Because the quick bioactive response in SBF, the capacity to host biomolecules in their pores and to release therapeutic concentrations of Ca2+ and Cu2+ ions, MBGs of the nitrate families are proposed as excellent biomaterials for bone regeneration.
Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits
(Acta Biomaterialia, 2024) García Lamas, Lorena; Lozano Borregón, Daniel; Jiménez Díaz, Verónica; Bravo Giménez, Beatriz; Sánchez Salcedo, Sandra; Abella, Mónica; Desco, Manuel; Jiménez Holguín, Javier; Vallet Regí, María Dulce Nombre; Cecilia López, David; Salinas Sánchez, Antonio Jesús
In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are ad- vanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2 –10CaO–5P2 O5 - x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rab- bits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the os- teostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteo- statin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice.
New photocrosslinked 3D foamed scaffolds based on GelMA copolymers: potential application in bone tissue engineering
(Gels, 2023) Pablos Lagartos, Jesús Luis; Jiménez Holguín, Javier; Sánchez Salcedo, Sandra; Salinas Sánchez, Antonio Jesús; Corrales, Teresa; Vallet Regí, María Dulce Nombre; MDPI
The production of customized polymeric hydrogels in the form of 3D scaffolds with application in bone tissue engineering is currently a topic of great interest. Based on gelatin methacryloyl (GelMa) as one of the most popular used biomaterials, GelMa with two different methacryloylation degrees (DM) was obtained, to achieve crosslinked polymer networks by photoinitiated radical polymerization. In this work, we present the obtention of new 3D foamed scaffolds based on ternary copolymers of GelMa with vinylpyrrolidone (VP) and 2-hydroxyethylmethacrylate (HEMA). All biopolymers obtained in this work were characterized by infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA), whose results confirm the presence of all copolymers in the crosslinked biomaterial. In addition, scanning electron microscopy (SEM) pictures were obtained verifying the presence of the porosity created by freeze-drying process. In addition, the variation in its swelling degree and its enzymatic degradation in vitro was analyzed as a function of the different copolymers obtained. This has allowed us to observe good control of the variation in these properties described above in a simple way by varying the composition of the different comonomers used. Finally, with these concepts in mind, biopolymers obtained were tested through assessment of several biological parameters such as cell viability and differentiation with MC3T3-E1 pre-osteoblastic cell line. Results obtained show that these biopolymers maintain good results in terms of cell viability and differentiation, along with tunable properties in terms of hydrophilic character, mechanical properties and enzymatic degradation. © 2023 by the authors.
Strontium-Modified Scaffolds Based on Mesoporous Bioactive Glasses/Polyvinyl Alcohol Composites for Bone Regeneration
(Materials, 2020) Jiménez Holguín, Javier; López Hidalgo, Álvaro; Sánchez Salcedo, Sandra; Peña Martínez, Juan; Vallet Regí, María Dulce Nombre; Salinas Sánchez, Antonio J.
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 with the scaffolds confirmed the cytocompatibility of the three compositions investigated. Nevertheless, the scaffold containing 2.5% of SrO induced the best cellular proliferation showing the potential of this scaffold as a candidate to be further investigated in vitro and in vivo, aiming to be clinically used for bone regeneration applications in non-load bearing sites.
Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo
(Revista Española de Cirugía Ortopédica y Traumatología, 2023) García Lamas, L.; Sánchez Salcedo, Sandra; Jiménez Díaz, V.; Bravo Giménez, B.; Cabañas Criado, María Victoria; Peña López, Juan; Román, J.; Jiménez Holguín, Javier; Abella, M.; Desco, M.; Lozano Borregón, Daniel; Cecilia López, D.; Salinas Sánchez, Antonio Jesús
Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto.
Cu-Doped Hollow Bioactive Glass Nanoparticles for Bone Infection Treatment
(Pharmaceutics, 2022) Jiménez Holguín, Javier; Sánchez Salcedo, Sandra; Cicuéndez Maroto, Mónica; Vallet Regí, María Dulce Nombre; Salinas, Antonio J.
In search of new approaches to treat bone infection and prevent drug resistance development, a nanosystem based on hollow bioactive glass nanoparticles (HBGN) of composition 79.5SiO2-(18-x)CaO-2.5P2O5-xCuO (x = 0, 2.5 or 5 mol-% CuO) was developed. The objective of the study was to evaluate the capacity of the HBGN to be used as a nanocarrier of the broad-spectrum antibiotic danofloxacin and source of bactericidal Cu2+ ions. Core-shell nanoparticles with specific surface areas close to 800 m2/g and pore volumes around 1 cm3/g were obtained by using hexadecyltrimethylammonium bromide (CTAB) and poly(styrene)-block-poly(acrylic acid) (PS-b-PAA) as structure-directing agents. Flow cytometry studies showed the cytocompatibility of the nanoparticles in MC3T3-E1 pre-osteoblastic cell cultures. Ion release studies confirmed the release of non-cytotoxic concentrations of Cu2+ ions within the therapeutic range. Moreover, it was shown that the inclusion of copper in the system resulted in a more gradual release of danofloxacin that was extended over one week. The bactericidal activity of the nanosystem was evaluated with E. coli and S. aureus strains. Nanoparticles with copper were not able to reduce bacterial viability by themselves and Cu-free HBGN failed to reduce bacterial growth, despite releasing higher antibiotic concentrations. However, HBGN enriched with copper and danofloxacin drastically reduced bacterial growth in sessile, planktonic and biofilm states, which was attributed to a synergistic effect between the action of Cu2+ ions and danofloxacin. Therefore, the nanosystem here investigated is a promising candidate as an alternative for the local treatment of bone infections.