RESUMEN

Hydroxyapatite coated metallic implants favorably combine the required biocompatibility with the mechanical properties. As an alternative to the industrial coating method of plasma spraying with inherently potential deleterious effects, sol-gel methods have attracted much attention. In this study, the effects of intermediate silk fibroin and silk sericin layers on the protein adsorption capacity of hydroxyapatite films formed by a particulate sol-gel method were determined experimentally. The preparation of the layered silk protein/hydroxyapatite structures on glass substrates, and the effects of the underlying silk proteins on the topography of the hydroxyapatite coatings were described. The topography of the hydroxyapatite layer fabricated on the silk sericin was such that the hydroxyapatite particles were oriented forming an oriented crystalline surface. The model protein (bovine serum albumin) adsorption increased to 2.62 µg/cm2 on the latter surface as compared to 1.37 µg/cm2 of hydroxyapatite on glass without an intermediate silk sericin layer. The BSA adsorption on glass (blank), glass/c-HAp, glass/m-HAp, glass/sericin/c-HAp, and glass/sericin/m-HAp substrates, reported as decrease in BSA concentration versus contact time.

Asunto(s)

Materiales Biocompatibles Revestidos/farmacocinética , Durapatita/química , Fibroínas/química , Sericinas/química , Albúmina Sérica Bovina/farmacocinética , Adsorción , Animales , Bovinos , Cerámica/síntesis química , Cerámica/química , Cerámica/farmacocinética , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Durapatita/farmacocinética , Fibroínas/farmacocinética , Membranas Artificiales , Microscopía de Fuerza Atómica , Modelos Biológicos , Nanopartículas/química , Sericinas/farmacocinética , Seda/química , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Difracción de Rayos X

RESUMEN

An essential criterion for the selection of resorbable bioceramics is their ability to degrade inside human body within a reasonable time frame. Furthermore, if the bioceramic can release beneficial ions, such as strontium, as it degrades, recovery time might be shortened. The present study demonstrates that strontium-containing calcium sulfate (Sr,Ca)SO4 can fulfill these criteria. A long-term in vitro degradation analysis for 12 weeks using sintered (Sr,Ca)SO4 discs in phosphate buffered solution (PBS) was conducted. The sintered (Sr,Ca)SO4 disc was then implanted into defects in the distal femur of rats. The degradation rate of (Sr,Ca)SO4 discs showed a strong dependence on the Sr content. Similar results were observed between the long-term in vitro degradation analysis and the in vivo evaluation. The sintered (3.8%Sr,Ca)SO4 disc lost more than 80% of its initial weight after soaking in PBS with shaking at 37 °C for 12 weeks. After 12 weeks in vivo, the remaining volume of the (3.8%Sr,Ca)SO4 disc within the bone defect was ~25%. Over the same time period, new bone was formed at a relative volume of 40%. This study demonstrates the potential of (Sr,Ca)SO4 bioceramic, and the benefits of using a long-term degradation test during the evaluation of resorbable bioceramics.

Asunto(s)

Implantes Absorbibles , Materiales Biocompatibles/farmacocinética , Cerámica/farmacocinética , Animales , Materiales Biocompatibles/química , Biotransformación , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sulfato de Calcio/química , Sulfato de Calcio/farmacocinética , Cerámica/química , Técnicas In Vitro , Ensayo de Materiales/métodos , Ratas , Ratas Sprague-Dawley , Estroncio/química , Estroncio/farmacocinética , Factores de Tiempo

RESUMEN

Drug delivery technology is a promising way to enhance the therapeutic efficacy of drugs. The purpose of this study is to evaluate the physical and chemical properties of hydroxyapatite ceramic microspheres loaded with doxycycline (HADOX), their effects on in vitro osteoblast viability, and their antimicrobial activity, and to determine the effects of DOX on the healing of rat sockets after tooth extraction. The internal microsphere porosity was sensitive to the treatment used to adsorb DOX onto microsphere surface; HA microspheres without DOX presented 26% of pores, whereas HADOX0.15 microspheres presented 52.0%. An initial drug release of 49.15 µg/ml was observed in the first 24 hr. The minimal inhibitory concentration (MIC) tested against Enterococcus faecalis demonstrated that bacterial growth was inhibited for up to 7 days. Results of cell viability and cell proliferation did not indicate statistical differences in the metabolic activity of HADOX samples relative to HA without DOX microspheres (p > .05). After 1 week, a discreet inflammation reaction was observed in the control group, and after 6 weeks, newly-formed bone was observed in the HADOX0.15 (p < .05). The HADOX did not interfere in the bone repair and controlled the early inflammatory response. HADOX could be a promising biomaterial to promote bone repair in infected sites.

Asunto(s)

Cerámica , Doxiciclina , Sistemas de Liberación de Medicamentos , Durapatita , Microesferas , Osteoblastos/metabolismo , Animales , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Doxiciclina/química , Doxiciclina/farmacocinética , Doxiciclina/farmacología , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacología , Enterococcus faecalis/crecimiento & desarrollo , Femenino , Masculino , Ratones , Ratas , Ratas Wistar

RESUMEN

A novel bone scaffold containing bioceramic and biopolymer materials with an osteoinductive simvastatin molecule was developed to enhance bone regeneration. An oxidized cellulose nanofiber (OCNF)-Gelatin (Gel) hydrogel was loaded into a biphasic calcium phosphate (BCP) ceramic in which simvastatin was entrapped, resulting in a scaffold with both osteoconductive and osteoinductive properties. The fabricated scaffold showed interconnected porosity with micro- and macroporous orientation. After loading the OCNF-Gel (HG), the mechanical stability of the ceramic BCP scaffold was increased suitable for the application of hard tissue regeneration. Fourier-transform infrared spectroscopy showed that simvastatin was successfully coated on the BCPHG scaffolds. OCNF, with its slower degradation, may contribute to the sustained release of drug from the scaffold. Initially simvastatin was released from the scaffold at high levels, then was constantly and gradually released for up to 4 weeks. Pre-osteoblast MC3T3E1 cells were seeded on the scaffolds to investigate cell viability, morphology, and differentiation. The simvastatin-loaded BCPHG-S scaffolds showed better cell proliferation and spreading compared to other scaffolds. Immunostaining assays showed the expression of proteins responsible for osteogenic differentiation. Alkaline phosphatase and osteopontin were more highly expressed in the BCPHG-S scaffold than in other scaffolds. These results suggest that simvastatin-loaded BCPHG scaffolds provided physiological environments suitable for better osteogenic differentiation.

Asunto(s)

Diferenciación Celular/efectos de los fármacos , Celulosa Oxidada , Cerámica , Hidrogeles , Hidroxiapatitas , Nanofibras , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Simvastatina , Animales , Línea Celular , Celulosa Oxidada/química , Celulosa Oxidada/farmacocinética , Celulosa Oxidada/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Hidrogeles/química , Hidrogeles/farmacocinética , Hidrogeles/farmacología , Hidroxiapatitas/química , Hidroxiapatitas/farmacocinética , Hidroxiapatitas/farmacología , Ratones , Nanofibras/química , Nanofibras/uso terapéutico , Simvastatina/química , Simvastatina/farmacocinética , Simvastatina/farmacología

RESUMEN

Microneedle arrays (MNAs) are a promising mean to administer vaccines. Without the need of highly trained personnel, MNAs can be applied to deliver vaccines into the dermis, which is well equipped to initiate potent immune responses. While vaccination using dissolving microneedle arrays has been extensively investigated, the use of solid nanoporous MNAs (npMNAs) to deliver vaccines remained largely unexplored. In this report we investigated whether npMNAs with an average pore size of 80 nm, can be used for influenza vaccination based on recombinant hemagglutinin (HA) protein of the 2009 pandemic H1N1 (pH1N1) virus. Fluorescently labeled HA loaded in the npMNAs was effectively delivered into the skin of mouse ears, as a result of a diffusion-based process. Compared to intramuscular immunization, intradermal HA vaccination of mice using npMNAs elicited high levels of HA antigen specific antibodies, with pH1N1 hemagglutination inhibition and neutralization activity. Moreover, mice vaccinated with pH1N1 HA loaded npMNAs were completely protected against a potentially lethal challenge with mouse adapted pH1N1 virus. These results illustrate that intradermal subunit vaccine immunization using npMNAs is a promising approach to facilitate effective vaccination.

Asunto(s)

Hemaglutininas/administración & dosificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Microinyecciones/métodos , Nanoporos , Vacunación/métodos , Animales , Cerámica/química , Cerámica/farmacocinética , Perros , Hemaglutininas/química , Hemaglutininas/metabolismo , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/fisiología , Vacunas contra la Influenza/química , Vacunas contra la Influenza/farmacocinética , Gripe Humana/inmunología , Gripe Humana/metabolismo , Células de Riñón Canino Madin Darby , Ratones , Microinyecciones/instrumentación , Agujas , Vacunación/instrumentación

RESUMEN

A novel bioglass composition (BGMS10), containing strontium and magnesium and characterized by an ultra-high crystallization temperature, is here employed for the first time to produce different composites with the addition of specific amounts of hydroxyapatite. After an investigation of the samples' bioactivity in vitro in a simulated body fluid solution (SBF) - according to a widely used protocol -, the biocompatibility of the new materials was tested with respect to murine fibroblasts both by direct and indirect tests, in order to evaluate possible cytotoxic effects of the materials' eluates. Although none of the samples were cytotoxic and their bioactivity in SBF increased with the increasing amount of the glass in the composite, thus showing the best performance in the case of pure BGMS10 glass, the findings of the biological investigation did not confirm those arising from the SBF assay. Surprisingly, while the composites with the lowest glass amount showed an enhanced biocompatibility in direct tests, on the contrary their biological responsiveness is typically lower in the indirect ones, based on filtered materials' extracts. This fact could be ascribed to the high release of particulate from the composites, which are more porous than the glassy samples: in fact, such pronounced dissolution may affect both the cell viability and the absorbance readings used in the colorimetric assays. The pure BGMS10 glass showed the best biological response only in the cell proliferation test (which is an indirect contact test), being able to stimulate cell proliferation in particular after 24 h. For these reasons, when considering bioactive glasses and bioglass-based composites, the results of direct cell culture assays should be integrated with those obtained by indirect ones, while the findings regarding the in vitro bioactivity in SBF should be interpreted with great care.

Asunto(s)

Líquidos Corporales/química , Proliferación Celular/efectos de los fármacos , Cerámica , Ensayo de Materiales , Animales , Cerámica/farmacocinética , Cerámica/farmacología , Humanos , Magnesio/química , Magnesio/farmacocinética , Magnesio/farmacología , Ratones , Células 3T3 NIH , Estroncio/química , Estroncio/farmacocinética , Estroncio/farmacología

RESUMEN

In this study, bone tissue engineered scaffolds fabricated via powder-based 3D printing from hydroxyapatite (HA) and calcium sulphate (CaSO4) powders were investigated. The combination of using a fast resorbing CaSO4 based powder and the relatively slower HA powder represents a promising prospect for tuning the bioresorption of 3D printed (3DP) scaffolds. These properties could then be tailored to coincide with tissue growth rate for different surgical procedures. The manufactured scaffolds were infiltrated with poly(ε­caprolactone) (PCL). The PCL infiltrated the inter-particle spacing within the 3DP structures due to the nature of a loosely-packed powder bed and also covered the surface of ceramic-based scaffolds. Consequently, the average compressive strength, compressive modulus and toughness increased by 314%, 465% and 867%, respectively. The resorption behaviour of the 3DP scaffolds was characterised in vitro using a high-throughput system that mimicked the physiological environment and dynamic flow conditions relevant to the human body. A rapid release of CaSO4 between Day 0 and 28 was commensurate with a reduction in scaffold mass and compressive properties, as well as an increase in medium absorption. In spite of this, HA particles, connected by PCL fibrils, remained within the microstructure after 56 days resorption under dynamic conditions. Consequently, a high level of structural integrity was maintained within the 3DP scaffold. This study presented a porous PCL-HA-CaSO4 3DP structure with the potential to encourage new tissue growth during the initial stages of implantation and also offering sufficient structural and mechanical support during the bone healing phase.

Asunto(s)

Cerámica/química , Fuerza Compresiva , Poliésteres/química , Impresión Tridimensional , Andamios del Tejido/química , Cerámica/farmacocinética , Humanos , Poliésteres/farmacocinética

RESUMEN

There is increasing interest in biodegradable ceramic scaffolds for bone tissue engineering capable of in situ delivery of ionic species favoring bone formation. Strontium has been shown to be osteogenic, but strontium-containing drugs such as strontium ranelate, used in Europe for the treatment of osteoporosis, are now restricted due to clinical evidence of systemic effects. By doping fluorapatite-based glasses with strontium, we developed ceramic scaffolds with fully interconnected macroporosity and cell size similar to that of cancellous bone, that are also capable of releasing strontium. The crystallization behavior, investigated by XRD and SEM, revealed the formation of akermanite and fluorapatite at the surface of strontium-free glass-ceramic scaffolds, and strontium-substituted fluorapatite at the surface of the strontium-doped scaffolds. At 8 weeks after implantation in a rat calvarial critical size defect, scaffolds doped with the highest amount of strontium led to the highest mineral apposition rate. A significantly higher amount of newly-formed bone was found with the strontium-free glass-ceramic scaffold, and possibly linked to the presence of akermanite at the scaffold surface. We demonstrate by energy dispersive XRF analyses of skull sections that strontium was present in newly formed bone with the strontium-doped scaffolds, while a significant amount of fluorine was incorporated in newly formed bone, regardless of composition or crystallization state. STATEMENT OF SIGNIFICANCE: The present work demonstrates the in vivo action of strontium-containing glass-ceramic scaffolds. These bone graft substitutes are targeted at non load-bearing bone defects. Results show that strontium is successfully incorporated in newly formed bone. This is associated with a significantly higher Mineral Apposition Rate. The benefits of in situ release of strontium are demonstrated. The broader scientific impact of this works builds on the concept of resorbable ceramic scaffolds as reservoirs of ionic species capable of enhancing bone regeneration.

Asunto(s)

Apatitas , Sustitutos de Huesos , Cerámica , Osteogénesis/efectos de los fármacos , Cráneo , Estroncio , Andamios del Tejido/química , Animales , Apatitas/química , Apatitas/farmacocinética , Apatitas/farmacología , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sustitutos de Huesos/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Ratas , Cráneo/lesiones , Cráneo/metabolismo , Cráneo/patología , Estroncio/química , Estroncio/farmacocinética , Estroncio/farmacología

RESUMEN

The bone-induction capacity of a porous biphasic calcium phosphate (pBCP) using heterotopic implantation in mouse (mHI-model) and its efficacy as substitute for autograft in mandibular critical-size defect in rabbit (rabMCSD-model) was investigated. In mHI-model, pBCP was implanted into the thigh muscles and bone formation was histomorphometrically and immunohistochemically evaluated. In rabMCSD-model, 13 mm bone defects were treated with pBCP or autograft and bone repair comparatively evaluated by radiographic and histomorphometric methods. In mHI-model, formed bone and immunolabeling for bone morphogenetic protein-2 and osteopontin were observed in 90% of pBCP implanted samples after 12 weeks. In rabMCSD-model neither statistically significant difference was found in newly formed bone between pBCP and autograft groups at 4 weeks (18.8 ± 5.5% vs 27.1 ± 5.6%), 8 weeks (22.3 ± 2.7% vs 26.2 ± 5.1), and 12 weeks (19.6 ± 4.7% vs 19.6 ± 2.3%). At 12 weeks, the stability and contour of the mandible were restored in both treatments. Near tooth remaining, pBCP particles were covered by small amount of mineralized tissue exhibiting perpendicular attachments of collagen fiber bundles with histological characteristic of acellular cementum. Within the limitations of this study, it was concluded that pBCP is osteoinductive and able to stimulate the new formation of bone and cementum-like tissues in rabMCSD-model, suggesting that it may be an alternative to treatment of large bone defect and in periodontal regenerative therapy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1546-1557, 2018.

Asunto(s)

Sustitutos de Huesos , Cerámica , Hidroxiapatitas , Mandíbula , Traumatismos Mandibulares , Osteogénesis/efectos de los fármacos , Animales , Proteína Morfogenética Ósea 2/química , Proteína Morfogenética Ósea 2/farmacocinética , Proteína Morfogenética Ósea 2/farmacología , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sustitutos de Huesos/farmacología , Trasplante Óseo , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Modelos Animales de Enfermedad , Hidroxiapatitas/química , Hidroxiapatitas/farmacocinética , Hidroxiapatitas/farmacología , Masculino , Mandíbula/metabolismo , Mandíbula/patología , Traumatismos Mandibulares/metabolismo , Traumatismos Mandibulares/patología , Traumatismos Mandibulares/terapia , Ratones , Ratones Endogámicos BALB C , Conejos

RESUMEN

Chronic osteomyelitis and infected bone defects are substantial challenges faced by orthopaedic surgeons. In this study, vancomycin was loaded into mesoporous bioactive glass (MBG) to form a local antibiotic delivery system and then a bone tissue-engineering scaffold combining MBG and poly-(L-lactic-co-glycolic acid) (PLGA) was prepared by freeze-drying fabrication. In vitro degradation and water contact angle analysis suggested that the MBG-incorporated PLGA scaffold exhibited controlled degradability, stabilizing the pH of the surrounding environment and improved the hydrophilicity. Moreover, the presence of MBG provides a well-interconnected pore structure, to which human bone marrow-derived mesenchymal stem cells can attach, spread and proliferate, promoting upregulation of the expression of osteogenic markers. Thus, MBG/PLGA scaffolds exhibit better cytocompatibility and osteoblastic difierentiation properties compared with pure PLGA scaffolds. Vancomycin-loaded scaffolds have been found to yield sustained release that lasts for more than eight weeks in vitro. We tested the antibacterial performance of vancomycin-loaded scaffolds against Staphylococcus aureus, the most common bacteria isolated from infected bone. In vitro experiments demonstrated that loading vancomycin onto the scaffold promoted antibacterial activity and inhibited biofilm formation without deleterious effect on cytocompatibility. In conclusion, the novel inorganic-organic composites are considered potential materials for the treatment of infected bone defects.

Asunto(s)

Antibacterianos , Regeneración Ósea/efectos de los fármacos , Cerámica , Osteogénesis/efectos de los fármacos , Osteomielitis/tratamiento farmacológico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/fisiología , Vancomicina , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Humanos , Osteomielitis/metabolismo , Osteomielitis/patología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Porosidad , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/patología , Vancomicina/química , Vancomicina/farmacocinética , Vancomicina/farmacología

RESUMEN

Porous ceramics doped with silicon and pure ß-TCP were analyzed in terms of internal microstructure, cell behavior, and the percentage of newly formed bone. Additionally the materials were tested to determine which of the two had better properties to load and release vancomycin hydrochloride. Internal pore distribution and porosity were determined through high pressure mercury porosimetry and the specific surface area was measured by the Brunauer Emmet-Teller method. The proliferation and viability of the human osteoblast-like cell line MG-63 was studied to validate both materials. The materials were tested on eight New Zealand rabbits which created defects, 10 mm in diameter, in the calvaria bone. After 8 and 12 weeks a histological and histomorphometric analysis was performed. Si-ß-TCP showed a higher porosity and specific surface area. The cytocompatibility test revealed acceptable results in terms of proliferation and viability whereas the percentage of new bone was higher in Si-ß-TCP with a two-time study being statistically significant with 12 weeks of healing (p < 0.05).The vancomycin loaded within the ceramic scaffolds were burst released and the material had the ability to inhibit bacterial growth. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2307-2315, 2018.

Asunto(s)

Regeneración Ósea/efectos de los fármacos , Cerámica , Ensayo de Materiales , Osteoblastos/metabolismo , Silicio , Vancomicina , Animales , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacocinética , Fosfatos de Calcio/farmacología , Línea Celular , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Humanos , Porosidad , Conejos , Silicio/química , Silicio/farmacocinética , Silicio/farmacología , Vancomicina/química , Vancomicina/farmacocinética , Vancomicina/farmacología

RESUMEN

Despite many studies, the impact of ceramic particles on cell behavior remains unclear. The aim of the present study was to investigate the effects of nano-sized ceramic particles on fibroblastic cells. Fibroblasts (dermal fibroblasts freshly isolated from skin samples and WI26 fibroblastic cells) were cultured in a monolayer in the presence of alumina or cerium-zirconia particles (≈50 nm diameter) at two concentrations (100 or 500 µg ml-1). Fluorescent alumina particles were also used. The following properties were analyzed: cell morphology, cytoplasmic ceramic incorporation (using confocal and transmission electron microscopy) and migration (using a silicon insert). Sedimentation field-flow fractionation (SdFFF) was also used to evaluate the rate of incorporation of ceramic particles into the cells. Finally, after treatment with various concentrations of ceramic particles, fibroblasts were also included in a collagen type I lattice constituting a dermal equivalent (DE), and the collagen lattice retraction and cell proliferation were evaluated. In monolayer conditions, the presence of both alumina and cerium-zirconia ceramic particles did not cause any deleterious effects on cultured cells (dermal fibroblast and WI26 cells) and cell fate was not affected in any way by the presence of ceramic particles in the cytoplasm. Confocal (using fluorescent alumina particles) and electron microscopy (using both alumina and cerium-zirconia particles) showed that ceramic particles were internalized in the WI26 cells. Using fluorescent membrane labeling and fluorescent alumina particles, a membrane was observed around the particle-containing vesicles present in the cytoplasm. Electron microscopy on WI26 cells showed the presence of a classical bilayer membrane around the ceramic particles. Interestingly, SdFFF confirmed that some dermal fibroblasts contained many alumina ceramic particles while others contained very few; in WI26 cells, the uptake of alumina ceramic was more homogeneous. In DE, collagen lattice retraction and cell proliferation were unchanged when WI26 fibroblastic cells contained alumina or cerium-zirconia ceramic particles. Our data suggest that ceramic particles are internalized in the cells by endocytosis. The presence of ceramic particles in the cytoplasm has no affect on cell behavior, confirming the excellent biocompatibility of this material and anticipating a minimal harmful effect of potential wear debris.

Asunto(s)

Materiales Biocompatibles/toxicidad , Cerámica/toxicidad , Fibroblastos/efectos de los fármacos , Nanopartículas/toxicidad , Óxido de Aluminio/química , Óxido de Aluminio/toxicidad , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Línea Celular , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Cerámica/química , Cerámica/farmacocinética , Cerio/química , Cerio/toxicidad , Fibroblastos/citología , Fibroblastos/fisiología , Humanos , Ensayo de Materiales , Microscopía Confocal , Microscopía Electrónica de Transmisión , Nanopartículas/química , Circonio/química , Circonio/toxicidad

RESUMEN

The high alkali content bioactive glasses commonly used to regenerate bone in dental, orthopedic, and maxillofacial surgeries induce some cytotoxicity in surrounding tissues. The present study aims the ability of some alkali-free bioactive glasses compositions, recently developed by our research group, to stimulate human mesenchymal stem cells (hMSCs) differentiation into osteoblasts in comparison to 45S5 Bioglass® . The obtained results demonstrated that alkali-free bioactive glasses possess higher stimulating towards differentiation of hMSCs in comparison to the control 45S5 Bioglass® . The von Kossa assay demonstrated that all bioactive glasses studied were able to induce the appearance of calcium deposits even when the cells were cultured in DMEM, proving that these biomaterials per se induce hMSCs cell differentiation. It was also observed that in both cell culture medium used (DMEM, and osteogenesis differentiation medium) alkali-free bioactive glasses clearly induced the appearance of more calcium deposits than the 45S5 Bioglass® , indicating their greater ability to induce cell differentiation. In summary, these results indicate that alkali-free bioactive glasses are a safe and valid alternative to 45S5 Bioglass® . © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2360-2365, 2017.

Asunto(s)

Células de la Médula Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Cerámica/farmacocinética , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Adulto , Álcalis , Células de la Médula Ósea/citología , Células Cultivadas , Femenino , Vidrio , Humanos , Masculino , Ensayo de Materiales , Células Madre Mesenquimatosas/citología , Osteoblastos/citología

RESUMEN

Periodontal disease is associated with the destruction of periodontal tissues, along with other disorders/problems including inflammation of tissues and severe pain. This paper reports the synthesis of meloxicam (MX) immobilized biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) based electrospun (e-spun) fibers and films. Electrospinning was employed to produce drug loaded fibrous mats, whereas films were generated by solvent casting method. In-vitro drug release from materials containing varying concentrations of MX revealed that the scaffolds containing higher amount of drug showed comparatively faster release. During initial first few hours fast release was noted from membranes and films; however after around 5h sustained release was achieved. The hydrogels showed good swelling property, which is highly desired for soft tissue engineered implants. To investigate the biocompatibility of our synthesized materials, VERO cells (epithelial cells) were selected and cell culture results showed that these all materials were non-cytotoxic and also these cells were very well proliferated on these synthesized scaffolds. These properties along with the anti-inflammatory potential of our fabricated materials suggest their effective utilization in periodontital treatments.

Asunto(s)

Plásticos Biodegradables , Implantes de Medicamentos , Membranas Artificiales , Animales , Plásticos Biodegradables/química , Plásticos Biodegradables/farmacocinética , Plásticos Biodegradables/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Quitosano/química , Quitosano/farmacocinética , Quitosano/farmacología , Chlorocebus aethiops , Implantes de Medicamentos/química , Implantes de Medicamentos/farmacocinética , Implantes de Medicamentos/farmacología , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacología , Meloxicam , Enfermedades Periodontales , Alcohol Polivinílico/farmacocinética , Alcohol Polivinílico/farmacología , Tiazinas/química , Tiazinas/farmacocinética , Tiazinas/farmacología , Tiazoles/química , Tiazoles/farmacocinética , Tiazoles/farmacología , Células Vero

RESUMEN

Titanium (Ti4+ ) containing materials have been widely used in medical applications due to its associated bioactivity in vivo. This study investigates the replacement of Si4+ with Ti4+ within the system SiO2 -Na2 O-CaO-P2 O5 to determine its influence on glass structure. This strategy was conducted in order to control the glass solubility to further improve the cellular response. Ti4+ incorporation was found to have little influence on the glass transition temperature (Tg = 520 ± 8°C) and magic angle spinning-nuclear magnetic resonance (MAS-NMR) shifts (-80 ppm) up to additions of 18 wt %. However, at 30 wt % the Tg increased to 600°C and MAS-NMR spectra shifted to -88 ppm. There was also an associated reduction in glass solubility as a function of Ti4+ incorporation as determined by inductively coupled plasma optical emission spectroscopy where Si4+ (1649-44 mg/L) and Na+ (892-36 mg/L) levels greatly reduced while Ca2+ (3-5 mg/L) and PO43- (2-7 mg/L) levels remained relatively unchanged. MC3T3 osteoblasts were used for cell culture testing and it was determined that the Ti4+ glasses increased cell viability and also facilitated greater osteoblast adhesion and proliferation to the glass surface compared to the control glass. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1703-1712, 2016.

Asunto(s)

Cerámica , Ensayo de Materiales , Osteoblastos/metabolismo , Titanio , Animales , Línea Celular , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Ratones , Osteoblastos/citología , Titanio/química , Titanio/farmacocinética , Titanio/farmacología

RESUMEN

Over the past few years, nanoparticles and their role in drug delivery have been the centre of attraction as new drug delivery systems. Various forms of nanosystems have been designed, such as nanoclays, scaffolds and nanotubes, having numerous applications in areas such as drug loading, target cell uptake, bioassay and imaging. The present study discusses various types of nanoparticles, with special emphasis on ceramic nanocarriers. Ceramic materials have high mechanical strength, good body response and low or non-existing biodegradability. In this article, the various aspects concerning ceramic nanoparticles, such as their advantages over other systems, their cellular uptake and toxicity concerns are discussed in detail.

Asunto(s)

Cerámica/química , Portadores de Fármacos/química , Nanopartículas/química , Nanotecnología/métodos , Óxido de Aluminio/química , Fosfatos de Calcio/química , Cerámica/farmacocinética , Cerámica/toxicidad , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidad , Composición de Medicamentos , Liberación de Fármacos , Compuestos Férricos/química , Humanos , Nanopartículas/toxicidad , Dióxido de Silicio/química , Titanio/química , Circonio/química

RESUMEN

Novel chitosan-polyvinyl pyrrolidone/45S5 Bioglass® (CS-PVP/BG) scaffolds were prepared via foam replication and chemical cross-linking techniques. The pristine BG, CS-PVP coated BG and genipin cross-linked CS-PVP/BG (G-CS-PVP/BG) scaffolds were synthesized and characterized in terms of chemical composition, physical structure and morphology respectively. Resistance to enzymatic degradation of the scaffold is improved significantly with the use of genipin cross-linked CS-PVP. The bio-effects of scaffolds on MC3T3-E1 osteoblast-like cells were evaluated by studying cell viability, adhesion and proliferation. The CCK-8 assay shows that cell viability on the resulting G-CS-PVP/BG scaffold is improved obviously after cross-linking of genipin. Cell skeleton images exhibit that well-stretched F-actin bundles are obtained on the G-CS-PVP/BG scaffold. SEM results present significant improvement on the cell adhesion and proliferation for cells cultured on the G-CS-PVP/BG scaffold. The drug release performance on the as-synthesized scaffold was studied in a phosphate buffered saline (PBS) solution. Vancomycin is found to be released in burst fashion within 24h from the pristine BG scaffold, however, the release period from the G-CS-PVP/BG scaffold is enhanced to 7days, indicating improved drug release properties of the G-CS-PVP/BG scaffold. Our results suggest that the G-CS-PVP/BG scaffolds possess promising physicochemical properties, sustained drug release capability and good biocompatibility for MC3T3-E1 cells' proliferation and adhesion, suggesting their potential applications in areas such as MC3T3-E1 cell stimulation and bone tissue engineering.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Cerámica , Quitosano , Vidrio , Iridoides , Osteoblastos/metabolismo , Povidona , Animales , Adhesión Celular/efectos de los fármacos , Línea Celular , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Quitosano/química , Quitosano/farmacocinética , Quitosano/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Vidrio/química , Iridoides/química , Iridoides/farmacocinética , Iridoides/farmacología , Ratones , Osteoblastos/citología , Povidona/química , Povidona/farmacocinética , Povidona/farmacología

RESUMEN

Hydroxyapatite (HA) is widely used as a bioactive ceramics as it forms a chemical bond with bone. However, the drawback to using this material is its inferior mechanical properties. In this research, surface corrosion and disintegration of nanoscaled HA in a dog were studied, and the mechanism by which phase-pure HA dissolved in vivo was investigated. Biological properties of HA in vivo are affected by the grain-boundary dissolution followed by a surface corrosion and microstructural disintegration. This kind of dissolution process, apparently evidenced at the grain boundary, causes particle generation, which indicates that both long-term bone in-growth and mechanical properties can dramatically deteriorate. Implant dissolution by osteoclasts in vivo is also observed on the surface of hydroxyapatite. Implant surface showed an aggressive corrosion by an osteoclast resorption. Severe and deeper dissolution underwent close to osteoclast resulting in formation of smaller and more round particle shape.

Asunto(s)

Sustitutos de Huesos , Cerámica , Durapatita , Osteoclastos/metabolismo , Animales , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sustitutos de Huesos/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Corrosión , Perros , Durapatita/química , Durapatita/farmacocinética , Durapatita/farmacología , Masculino , Osteoclastos/patología

RESUMEN

Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process.

Asunto(s)

Sustitutos de Huesos , Cerámica , Hierro , Ensayo de Materiales , Animales , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sustitutos de Huesos/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Hierro/química , Hierro/farmacocinética , Hierro/farmacología , Masculino , Ovinos

RESUMEN

Infection remains a significant problem associated with biomedical implants and orthopedic surgeries, especially in revision total joint replacements. Recent advances in antibiotic-releasing bone void fillers (BVF) provide new opportunities to address these types of device-related orthopedic infections that often lead to substantial economic burdens and reduced quality of life. We report improvements made in fabrication and scalability of an antibiotic-releasing polycaprolactone-calcium carbonate/phosphate ceramic composite BVF using a new solvent-free, molten-cast fabrication process. This strategy provides the ability to tailor drug release kinetics from the BVF composite based on modifications of the inorganic substrate and/or the polymeric component, allowing extended tobramycin release at bactericidal concentrations. The mechanical properties of the new BVF composite are comparable to many reported BVFs and validate the relative homogeneity of fabrication. Most importantly, fabrication quality controls are correlated with favorable drug release kinetics, providing bactericidal activity to 10 weeks in vitro when the polycaprolactone component exceeds 98% w/w of the total polymer fraction. Furthermore, in a time kill study, tobramycin-releasing composite fragments inhibited S. aureus growth over 48 h at inoculums as high as 10(9) CFU/mL. This customizable antibiotic-releasing BVF polymer-inorganic biomaterial should provide osseointegrative and osteoconductive properties while contributing antimicrobial protection to orthopedic sites requiring the use of bone void fillers.

Asunto(s)

Antibacterianos , Sustitutos de Huesos , Staphylococcus aureus/crecimiento & desarrollo , Tobramicina , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacocinética , Sustitutos de Huesos/farmacología , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacocinética , Fosfatos de Calcio/farmacología , Cerámica/química , Cerámica/farmacocinética , Cerámica/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacología , Tobramicina/química , Tobramicina/farmacocinética , Tobramicina/farmacología