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1.
J Orthop Surg Res ; 16(1): 108, 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33541384

RESUMEN

BACKGROUND: This study aimed to prepare the polymethylmethacrylate (PMMA) bone cement release system with different concentrations of enoxaparin sodium (ES) and to investigate the release characteristics of ES after loading into the PMMA bone cement. METHODS: In the experimental group, 40 g Palacos®R PMMA bone cement was loaded with various amount of ES 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, respectively. The control group was not loaded with ES. Scanning electron microscopy (SEM) was used to observe the surface microstructure of the bone cement in the two groups. In the experiment group, the mold was extracted continuously with pH7.4 Tris-HCL buffer for 10 days. The extract solution was collected every day and the anti-FXa potency was measured. The experiment design and statistical analysis were conducted using a quantitative response parallel line method. RESULTS: Under the SEM, it was observed that ES was filled in the pores of PMMA bone cement polymer structure and released from the pores after extraction. There was a burst effect of the release. The release amount of ES on the first day was 0.415, 0.858, 1.110, 1.564, 1.952, and 2.513, respectively, from the six groups with various ES loading amount of 4000, 8000, 12,000, 16,000, 20,000, and 24,000 AXaIU, all reaching the peak of release on the first day. The release decreased rapidly on the next day and entered the plateau phase on the fourth day. CONCLUSION: The prepared ES-PMMA bone cement has high application potential in orthopedic surgery. ES-PMMA bone cement shows good drug release characteristics. The released enoxaparin sodium has a local anti-coagulant effect within 24 h after application, but it will not be released for a long time, which is complementary to postoperative anti-coagulation therapy.


Asunto(s)
Cementos para Huesos , Liberación de Fármacos , Enoxaparina , Polimetil Metacrilato , Anticoagulantes/administración & dosificación , Cementos para Huesos/química , Enoxaparina/administración & dosificación , Enoxaparina/farmacología , Polimetil Metacrilato/química , Porosidad , Trometamina
2.
J Biomater Appl ; 35(3): 385-404, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32567484

RESUMEN

One of the most common prophylactic techniques to solve prosthetic joint infection (PJI) is incorporation of antibiotics into acrylic bone cement to prevent bacterial colonization and proliferation by providing local antibiotic delivery directly at the implant site. Further, there has been a significant concern over the efficacy of commonly used antibiotics within bone cement due to the rise in multi-drug resistant (MDR) microorganisms. Selenium is an essential trace element that has multiple beneficial effects for human health and its chemotherapeutic action is well known. It was reported that nanostructured selenium enhanced bone cell adhesion and has an increased osteoblast function. In this context, we used the selenium nanoparticles (SeNPs) to improve antibacterial and antioxidant properties of poly (methyl methacrylate) (PMMA) and tri calcium phosphate (TCP)-based bone cements, and to reduce of the infection risk caused by orthopedic implants. As another novelty of this study, we proposed phosphatidylcholine (PC) as a unique and natural stabilizer in the synthesis of selenium nanoparticles. After the structural analysis of the prepared bone cements was performed, in vitro osteointegration and antibacterial efficiency were tested using MC3T-E1 (mouse osteoblastic cell line) and SaOS-2 (human primary osteogenic sarcoma) cell lines, and S. aureus (Gram positive) and E.coli (Gram negative) strains, respectively. More importantly, PC-SeNPs-reinforced bone cements exhibited significant effect against E. coli, compared to S. aureus and a dose-dependent antibacterial activity against both bacterial strains tested. Meanwhile, these bone cements induced the apoptosis of SaOS-2 through increased reactive oxygen species without negatively influencing the viability of the healthy cell line. Furthermore, the obtained confocal images revealed that PC-SeNPs (103.7 ± 0.56 nm) altered the cytoskeletal structure of SaOS-2 owing to SeNPs-induced apoptosis, when MC3T3-E1 cells showed a typical spindle-shaped morphology. Taken together, these results highlighted the potential of PC-SeNPs-doped bone cements as an effective graft material in bone applications.


Asunto(s)
Antibacterianos/química , Cementos para Huesos/química , Nanopartículas/química , Fosfatidilcolinas/química , Selenio/química , Animales , Antibacterianos/farmacología , Antioxidantes/química , Apoptosis/efectos de los fármacos , Fosfatos de Calcio/química , Línea Celular , Escherichia coli/efectos de los fármacos , Humanos , Ratones , Osteoblastos/química , Osteoblastos/metabolismo , Polimetil Metacrilato/química , Especies Reactivas de Oxígeno/química , Selenio/farmacología , Staphylococcus aureus/efectos de los fármacos
3.
Sci Rep ; 10(1): 7554, 2020 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-32371998

RESUMEN

In general, osteomyelitis is treated with antibiotics, and in severe cases, the inflammatory bone tissue is removed and substituted with poly (methyl methacrylate) (PMMA) beads containing antibiotics. However, this treatment necessitates re-surgery to remove the inserted PMMA beads. Moreover, rifampicin, a primary heat-sensitive antibiotic used for osteomyelitis, is deemed unsuitable in this strategy. Three-dimensional (3D) printing technology has gained popularity, as it facilitates the production of a patient-customized implantable structure using various biodegradable biomaterials as well as controlling printing temperature. Therefore, in this study, we developed a rifampicin-loaded 3D scaffold for the treatment of osteomyelitis using 3D printing and polycaprolactone (PCL), a biodegradable polymer that can be printed at low temperatures. We successfully fabricated rifampicin-loaded PCL 3D scaffolds connected with all pores using computer-aided design and manufacturing (CAD/CAM) and printed them at a temperature of 60 °C to prevent the loss of the antibacterial activity of rifampicin. The growth inhibitory activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the representative causative organisms of osteomyelitis, was confirmed. In addition, we optimized the rifampicin-loading capacity that causes no damage to the normal bone tissues in 3D scaffold with toxicity evaluation using human osteoblasts. The rifampicin-releasing 3D scaffold developed herein opens new possibilities of the patient-customized treatment of osteomyelitis.


Asunto(s)
Antibacterianos/farmacología , Calor , Osteoblastos/efectos de los fármacos , Osteomielitis/tratamiento farmacológico , Impresión Tridimensional , Materiales Biocompatibles/química , Línea Celular , Proliferación Celular , Diseño de Fármacos , Escherichia coli/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Polimetil Metacrilato/química , Rifampin/farmacología , Staphylococcus aureus/efectos de los fármacos , Andamios del Tejido , Investigación Biomédica Traslacional
4.
Ther Drug Monit ; 42(3): 452-459, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31913865

RESUMEN

BACKGROUND: Although continuous hemodiafiltration (CHDF) is often performed in critically ill patients during sepsis treatment, the pharmacokinetics of vancomycin (VCM) during CHDF with a polymethylmethacrylate hemofilter (PMMA-CHDF) have not been revealed. In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CLhemofilter). METHODS: This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed, and CLhemofilter was assessed. RESULTS: Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions for CHDF were 107.5 ± 18.3 mL/min for blood flow rate and 26.3 ± 6.3 mL/kg/h for effluent flow rate. The mean parameter estimates were distribution volume of the central compartment (V1), 59.1 L; clearance of the central compartment (CL1), 1.35 L/h; distribution volume of the peripheral compartment (V2), 56.1 L; and clearance of the peripheral compartment (CL2), 3.65 L/h. BW and SOFA score were significantly associated with V1 (P < 0.05) and CL1 (P < 0.05), respectively, and were thus selected as covariates in the final model. The estimated dosage of VCM to achieve a target area under the concentration-time curve/minimum inhibitory concentration ≥400 was 27.1 mg/kg for loading and 9.7 mg/kg every 24 hours for maintenance; these dosages were affected by BW and SOFA score. Mean CLhemofilter obtained from 8 patients was 1.35 L/h, which was similar to CL1. CONCLUSIONS: The authors clarified the pharmacokinetics and CLhemofilter of VCM in PMMA-CHDF patients. The PK of VCM in patients undergoing CHDF appeared to vary not only with the CHDF setting and BW but also with SOFA score.


Asunto(s)
Antibacterianos/farmacocinética , Terapia de Reemplazo Renal Continuo/métodos , Hemodiafiltración/métodos , Polimetil Metacrilato/química , Vancomicina/farmacocinética , APACHE , Adulto , Anciano , Anciano de 80 o más Años , Peso Corporal , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
5.
Mater Sci Eng C Mater Biol Appl ; 108: 110460, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31923975

RESUMEN

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe3O4 nanoparticles and the antitumor drug doxorubicin (DOX/Fe3O4@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe3O4@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe3O4 nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe3O4@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe3O4@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe3O4@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.


Asunto(s)
Cementos para Huesos , Neoplasias Óseas/terapia , Hipertermia Inducida , Nanopartículas de Magnetita , Osteosarcoma/terapia , Animales , Cementos para Huesos/química , Cementos para Huesos/farmacología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Osteosarcoma/metabolismo , Osteosarcoma/patología , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Colloids Surf B Biointerfaces ; 188: 110763, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31896518

RESUMEN

For the first time, an electrophoretic deposition (EPD) method has been developed for the deposition of polymethylmethacrylate (PMMA) and PMMA-alumina films for biomedical implant applications. The proposed biomimetic approach was based on the use of a bile salt, sodium cholate (NaCh), which served as a multifunctional solubilizing, charging, dispersing and film-forming agent. Investigations revealed PMMA-Ch- and PMMA-alumina interactions, which facilitated the deposition of PMMA and PMMA-alumina films. This approach allows for the use of a non-toxic water-ethanol solvent for PMMA. The proposed deposition strategy can also be used for co-deposition of PMMA with other functional materials. The PMMA and composite films were tested for biomedical implant applications. The PMMA-alumina films showed statistically improved metabolic results compared to both the bare stainless steel substrate and pure PMMA films. Alkaline phosphatase (ALP) activity affirmed the bioactivity and osteoconductive potential of PMMA and composite films. PMMA-alumina films showed greater ALP activity than both the PMMA-coated and uncoated stainless steel.


Asunto(s)
Investigación Biomédica , Osteosarcoma/metabolismo , Polimetil Metacrilato/metabolismo , Fosfatasa Alcalina/metabolismo , Óxido de Aluminio/química , Óxido de Aluminio/metabolismo , Electroforesis , Humanos , Osteosarcoma/patología , Tamaño de la Partícula , Polimetil Metacrilato/química , Propiedades de Superficie
7.
Lab Chip ; 19(21): 3706-3713, 2019 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-31577312

RESUMEN

Here, we report a simple yet reliable method for bonding poly(methyl methacrylate) (PMMA) to polyethylene terephthalate (PETE) track-etched membranes using (3-glycidyloxypropyl)trimethoxysilane (GLYMO), which enables reliable cytotoxicity tests in a microfluidic device impermeable to small molecules, such as anti-cancer drugs. The porous PETE membranes treated with 5% GLYMO were assembled with microfluidic channel-engraved PMMA substrates after air plasma treatment for 1 minute, followed by heating at 100 °C for 2 minutes, which permits irreversible and complete bonding to be achieved within 1 h. The bonding strength between the two substrates (1.97 × 107 kg m-2) was robust enough to flow culture medium through the device without leakage even at a gauge pressure of above 135 kPa. For validation of its utility in drugs testing, we successfully demonstrated that human lung adenocarcinoma cells cultured in the PMMA devices show more reliable cytotoxicity results for vincristine in comparison to conventional polydimethylsiloxane (PDMS) devices due to the inherent property of PMMA of it being impervious to small molecules. Given that the current organ-on-a-chip fabrication methods mostly rely on PDMS, this bonding strategy will expand simple fabrication capability using various thermoplastics and porous track-etched membranes, and allow us to create 3D-micro-constructs that more precisely mimic organ-level physiological conditions.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/metabolismo , Dispositivos Laboratorio en un Chip , Membranas Artificiales , Tereftalatos Polietilenos/química , Polimetil Metacrilato/química , Células A549 , Evaluación Preclínica de Medicamentos , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Porosidad
8.
Theranostics ; 9(14): 4192-4207, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31281541

RESUMEN

Background: Minimally invasive modalities are of great interest in the field of treating bone tumors. However, providing reliable mechanical support and fast killing of tumor cells to achieve rapid recovery of physical function is still challenging in clinical works. Methods: A material with two functions, mechanical support and magnetic thermal ablation, was developed from Fe3O4 nanoparticles (NPs) distributed in a polymethylmethacrylate (PMMA) bone cement. The mechanical properties and efficiency of magnetic field-induced thermal ablation were systematically and successfully evaluated in vitro and ex vivo. CT images and pathological examination were successfully applied to evaluate therapeutic efficacy with a rabbit bone tumor model. Biosafety evaluation was performed with a rabbit in vivo, and a cytotoxicity test was performed in vitro. Results: An NP content of 6% Fe3O4 (PMMA-6% Fe3O4, mFe: 0.01 g) gave the most suitable performance for in vivo study. At the 56-day follow-up after treatment, bone tumors were ablated without obvious side effects. The pathological examination and new bone formation in CT images clearly illustrate that the bone tumors were completely eliminated. Correspondingly, after treatment, the tendency of bone tumors toward metastasis significantly decreased. Moreover, with well-designed mechanical properties, PMMA-6%Fe3O4 implantation endowed tumor-bearing rabbit legs with excellent bio-mimic bone structure and internal support. Biosafety evaluation did not induce an increase or decrease in the immune response, and major functional parameters were all at normal levels. Conclusion: We have presented a novel, highly efficient and minimally invasive approach for complete bone tumor regression and bone defect repair by magnetic thermal ablation based on PMMA containing Fe3O4 NPs; this approach shows excellent heating ability for rabbit VX2 tibial plateau tumor ablation upon exposure to an alternating magnetic field (AMF) and provides mechanical support for bone repair. The new and powerful dual-function implant is a promising minimally invasive agent for the treatment of bone tumors and has good clinical translation potential.


Asunto(s)
Neoplasias Óseas/terapia , Compuestos Férricos/química , Polimetil Metacrilato/química , Animales , Hipertermia Inducida/métodos , Nanopartículas de Magnetita/química , Ratones , Conejos , Ratas
9.
Food Chem ; 300: 125205, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31330372

RESUMEN

For efficient extraction of amplifiable DNA from edible vegetable oils, we developed a novel DNA extraction approach based on the non-silica-based dipolar nanocomposites. The nanoparticle comprises a hydrophilic polymethyl methacrylate core with abundant capillaries, hydrophilic vesicles decorated with molecules having DNA affinity and a coating hydrophobic polystyrene layer. The nanoparticles are soluble in oil, adsorb the DNA from the aqueous phase and gave a high DNA recovery ratio. All DNA extracts from fully refined vegetable oil soybean, peanut, rapeseed, and cottonseed oils, including their blends, were sufficiently pure to be amplified by real-time PCR targeting the chloroplast ribulose-1,5-bisphosphate gene (rbcL), therefore, the species of origin and their ratios in mixed vegetable oils blended from two or three oil-species could be determined. These results indicate that the novel DNA isolation and real-time PCR kit is a simple, sensitive and efficient tool for the species identification and traceability in refined vegetable oils.


Asunto(s)
ADN de Plantas/aislamiento & purificación , Nanopartículas/química , Aceites de Plantas/química , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Verduras/genética , Fraccionamiento Químico/métodos , Cloroplastos/genética , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Polimetil Metacrilato/química , Ribulosafosfatos/genética , Dióxido de Silicio
10.
Spine J ; 19(11): 1871-1884, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31202837

RESUMEN

BACKGROUND CONTEXT: Polymethylmethacrylate (PMMA) is the most commonly used filling material when performing percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures. However, there are some inherent and unavoidable drawbacks with the clinical use of PMMA. PMMA bone cement tends to leak during injection, which can lead to injury of the spinal nerves and spinal cord. Moreover, the mechanical strength of PMMA-augmented vertebral bodies is extraordinary and this high level of mechanical strength might predispose to adjacent vertebral fractures. A novel biodegradable calcium phosphate-based nanocomposite (CPN) for PKP augmentation has recently been developed to potentially avoid these issues. PURPOSE: By comparison with PMMA, the leakage characteristics, biomechanical properties, and dispersion of CPN were evaluated when used for PKP. STUDY DESIGN: Biomechanical evaluation and studies on the dispersion and anti-leakage properties of CPN and PMMA cements were performed and compared using cadaveric vertebral fracture model, sheep vertebral fracture model, and simulated rigid foam model. METHODS: Sheep vertebral bodies were decalcified by ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) to simulate osteoporosis in vitro. After compression to create wedge-shaped fractures using a self-designed fracture creation tool, human cadaveric vertebrae and decalcified sheep vertebrae were augmented by PKP. In addition, three L5 vertebral bodies from human cadavers were used in a contrast vertebroplasty (VP) augmentation experiment. Occurrence of cement leakage was observed and compared between CPN and PMMA during the process of vertebral augmentation. Open-cell rigid foam model (Sawbones#1522-507) was used to create a simulated leakage model for the evaluation of the leakage characteristics of CPN and PMMA with different viscosities. The augmentation effects of CPN and PMMA were evaluated in human cadaveric and decalcified sheep vertebral models and then compared to the results from solid rigid foam model (Sawbones#1522-23). The dispersion abilities of CPN and PMMA were evaluated via three methods as follows. The dispersion volume and dispersion ratio were calculated by three-dimensional reconstruction using human vertebral body CT scans; the ratio of cement area to injection volume was calculated from three-dimensional sections of micro-CT scans of a sheep vertebra; and the micro-CT images of cement dispersion in open-cell rigid foam model (Sawbones#1522-507) were compared between CPN and PMMA. This study was funded by the National Natural Science Foundation of China (No. 81622032, 190,000 dollars and No. 51672184, 90,600 dollars), Principal Project of Natural Science Research of Jiangsu Higher Education Institutions (No. 17KJA180011, 22,000 dollars), and Jiangsu Innovation and Entrepreneurship Program (146,000 dollars). RESULTS: There was no significant difference in vertebral height between CPN and PMMA during PKP augmentation and both cements restored the vertebral height after augmentation. In PKP augmentation experiment, posterior wall cement leakage occurred in 75% of human vertebrae augmented with PMMA; however, no leakage occurred in human vertebrae augmented with CPN. Anterior leakage occurred in all vertebrae augmented by PMMA, while in only 75% of vertebra augmented by CPN. Furthermore, CPN and PMMA had completely different leakage patterns in the simulated rigid foam model whether administered at the same injection speed or under the same injection force, suggesting that CPN has anti-leakage characteristics. The augmentation in human cadaveric vertebrae was lower with CPN compared to PMMA (1,668±816 N vs. 2,212±813 N, p=.459, respectively), but this difference was not significant. The augmentation force in sheep vertebral bodies reached 1,393±433 N when augmented with PMMA, but 1,108±284 N when augmented with CPN. The dispersion of CPN was better, and the dispersion volume and ratio were greater, with CPN than with PMMA. Imaging of the open-cell rigid foam model showed completely different dispersion modes for CPN and PMMA. After injection, the PMMA cement formed a contracted clump in the open-cell rigid foam model. However, the CPN cement extended many antennae outward, appearing to spread to the surrounding area. The surface areas of the CPN cement blocks with different liquid-to-solid ratios were significantly larger than the surface area of the PMMA cement in the open-cell rigid foam model (p<.05). CONCLUSIONS: CPN has anti-leakage properties, which might be related to its high viscosity and viscoplasticity. CPN had a slightly lower augmentation force than PMMA when used in cadaveric vertebrae, decalcified sheep vertebrae, and in the standard rigid foam model. However, CPN diffused more easily into cancellous bone than did PMMA and encapsulated bone tissue during the dispersion process. The excellent dispersion of CPN generated better interdigitation with cancellous bone, which may be why the augmentation effect of CPN is similar to that of PMMA. CLINICAL SIGNIFICANCE: Biodegradable CPN is a potential alternative to PMMA cement in PKP surgery, in which CPN is likely to reduce the cement leakage during the surgery and avoid the post-surgery complications caused by excessive strengths and nondegradability of PMMA cement.


Asunto(s)
Cementos para Huesos/uso terapéutico , Fosfatos de Calcio/uso terapéutico , Fracturas por Compresión/cirugía , Cifoplastia/métodos , Nanocompuestos , Fracturas Osteoporóticas/cirugía , Polimetil Metacrilato/uso terapéutico , Fracturas de la Columna Vertebral/cirugía , Anciano , Anciano de 80 o más Años , Animales , Fenómenos Biomecánicos , Cementos para Huesos/química , Cadáver , Fosfatos de Calcio/química , Femenino , Fracturas por Compresión/diagnóstico por imagen , Humanos , Masculino , Nanocompuestos/química , Fracturas Osteoporóticas/diagnóstico por imagen , Polimetil Metacrilato/química , Complicaciones Posoperatorias , Ovinos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Viscosidad
11.
Colloids Surf B Biointerfaces ; 178: 44-55, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30826553

RESUMEN

Use of soluble factors is the most common strategy to induce osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, but it may raise potential side effects in vivo. The topographies of the substrate surfaces affect cell behavior, and this could be a promising approach to guide stem cell differentiation. Micropillars have been reported to modulate cellular and subcellular shape, and it is particularly interesting to investigate whether these changes in cell morphology can modulate gene expression and lineage commitment without chemical induction. In this study, poly(methyl methacrylate) (PMMA) films were decorated with square prism micropillars with different lateral dimensions (4, 8 and 16 µm), and the surface wettability of the substrates was altered by oxygen plasma treatment. Both, pattern dimensions and hydrophilicity, were found to affect the attachment, proliferation, and most importantly, gene expression of human dental pulp mesenchymal stem cells (DPSCs). Decreasing the pillar width and interpillar spacing of the square prism pillars enhanced cell attachment, cell elongation, and deformation of nuclei, but reduced early proliferation rate. Surfaces with 4 or 8 µm wide pillars/gaps upregulated the expression of early bone-marker genes and mineralization over 28 days of culture. Exposure to oxygen plasma increased wettability and promoted cell attachment and proliferation but delayed osteogenesis. Our findings showed that surface topography and chemistry are very useful tools in controlling cell behavior on substrates and they can also help create better implants. The most important finding is that hydrophobic micropillars on polymeric substrate surfaces can be exploited in inducing osteogenic differentiation of MSCs without any differentiation supplements.


Asunto(s)
Pulpa Dental/citología , Células Madre Mesenquimatosas/citología , Polimetil Metacrilato/química , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Osteogénesis/efectos de los fármacos , Polimetil Metacrilato/farmacología
12.
J Prosthet Dent ; 121(2): 347-352, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30143239

RESUMEN

STATEMENT OF PROBLEM: Studies of the color stability, relative translucency, and surface roughness of newly introduced computer-assisted design and computer-assisted manufacturing (CAD-CAM) prepolymerized poly(methyl methacrylate) (PMMA) denture base materials are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the color stability, relative translucency, and surface roughness of conventional and different prepolymerized CAD-CAM PMMA denture base materials after coffee thermocycling (CTC). MATERIAL AND METHODS: Six disk-shaped specimens (10×2 mm) were prepared from 3 different brands of prepolymerized CAD-CAM PMMA and a conventional heat-polymerized PMMA denture base material (N=24). Specimens were polished conventionally in 2 stages. The specimens were subjected to 5000 coffee thermocycles. The surface roughness (Ra) of each specimen was measured 3 times before and after CTC, using a contact profilometer, and the mean roughness (Ra) values were calculated. The color coordinates of the specimens were determined by using a noncontact spectroradiometer, and color differences and relative translucency parameter (RTP) values were calculated by using CIEDE2000 color difference and RTPCIEDE2000 formulas. ANOVA was used to analyze surface roughness values, CIEDE2000 color differences, and RTP values (α=.05). RESULTS: CTC did not change the color of the tested materials. However, with regard to relative translucency, 2-way ANOVA revealed a significant interaction between the material and CTC (P=.011). Also, although CTC increased the surface roughness of all tested materials (P=.031), Ra values were lower than the plaque accumulation threshold of Ra=0.2 µm. CONCLUSIONS: Mean color changes in all materials were clinically imperceptible after 5000 coffee thermocycles. One tested material had significantly lower relative translucency than other materials before and after CTC. The surface roughness values of all tested denture base materials were below the plaque accumulation threshold.


Asunto(s)
Bases para Dentadura , Polimetil Metacrilato/química , Café , Color , Diseño Asistido por Computadora , Materiales Dentales/química , Técnicas In Vitro , Ensayo de Materiales , Fenómenos Ópticos , Polimerizacion , Propiedades de Superficie
13.
Phys Med Biol ; 64(5): 055018, 2019 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-30572319

RESUMEN

Carbon ion radiotherapy is an attractive alternative to conventional radiotherapy, especially in case of deep-seated and radio-resistant tumors. As a consequence of inelastic nuclear reactions between primary particles and patient's tissues, the primary carbon ions may undergo nuclear fragmentation. The resulting decrease of primary ions and production of secondary fragments have to be carefully considered for accurate dose calculations in the treatment planning systems. The experimental data currently available provide only general information on carbon ion fragmentation and are not sufficient to cover the entire range of beam energies, target configurations and compositions relevant for radiotherapy. Therefore, new investigations were carried out to analyse the outcomes of the inelastic nuclear reaction processes on a single-ion-based approach. Measurements were performed at HIT, using 430 MeV/u carbon ion beams crossing water and PMMA targets. Unique in this method is the possibility of measuring number and type of fragments produced from each single carbon ion, provided that they are within the acceptance of the experimental apparatus. Concerning the amount of residual carbon ions behind water and PMMA targets with the same water equivalent thickness (WET), no significant differences were found. The experimental attenuation curve was well reproduced by the simulations. However, in the experiments, differences were observed regarding the amount of secondary fragments produced in water and in PMMA targets with the same WET. Differences were also found between experiments and simulations. These findings should be considered when dosimetric measurements are performed with PMMA instead of water phantoms. The found differences between experiments and simulations may contribute to improve the nuclear interaction and fragmentation models in Monte Carlo codes.


Asunto(s)
Carbono/química , Carbono/uso terapéutico , Radioterapia de Iones Pesados/métodos , Polimetil Metacrilato/química , Agua/química , Humanos , Método de Montecarlo , Fantasmas de Imagen , Radiometría , Planificación de la Radioterapia Asistida por Computador
14.
Anal Chem ; 90(15): 9025-9032, 2018 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-29992805

RESUMEN

Raman spectroscopy in combination with appropriate sample preparation strategies, for example, enrichment of bacteria on metal surfaces, has been proven to be a promising approach for rapidly diagnosing infectious diseases. Unfortunately, the fabrication of the required chip substrates is usually very challenging due to the lack of feasible instruments that can be used for quality control in the surface modification process. The intrinsically weak Raman signal of the biomolecules, employed for the enrichment of the micro-organisms on the chip surface, does not allow for monitoring of the successful immobilization by means of a Raman spectroscopic approach. Within this contribution, we demonstrate how a simple modification of a plain aluminum surface enables enhancement (or a decrease, if desired) of the Raman signal of molecules deposited on that surface. The manipulation of the Raman signal strength is achieved via exploiting interference effects that occur, if the highly reflective aluminum surface is modified with thin layers of transparent dielectrics like aluminum oxide. The thicknesses of these layers were determined by theoretical considerations and calculations. For the first time, it is shown that the interference effects can be used for the detection of biomolecules as well by investigating the siderophore ferrioxamine B. The observed degree of enhancement was approximately 1 order of magnitude. Moreover, the employed aluminum/aluminum oxide layers have been thoroughly characterized using atomic force and scanning electron microscopy as well as X-ray reflectometry and UV-Vis measurements.


Asunto(s)
Óxido de Aluminio/química , Aluminio/química , Deferoxamina/química , Compuestos Férricos/química , Polimetil Metacrilato/química , Espectrometría Raman/instrumentación , Diseño de Equipo , Propiedades de Superficie
15.
J Contemp Dent Pract ; 19(6): 732-738, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29959304

RESUMEN

AIM: This study aimed to evaluate the effect of the addition of various henna-which can have antifungal properties-on the surface roughness and hardness of polymethylmethacrylate (PMMA) denture base material. MATERIALS AND METHODS: A total of 99 rectangular-shaped (10 × 20 × 3 mm3) specimens were prepared from heat-cured acrylic resin and divided into one control group without the addition of henna and five test groups, which were prepared by adding Yamanihenna powder to polymer at concentrations of 1, 2.5, 5, 7.5, and 10 wt%. The polymer was added to the monomer, mixed, packed, and processed using the conventional water bath method. After processing, specimens were finished and polished, then kept in distilled water for 48 ± 2 hours. A profilom-eter and Vickers hardness tester were used to measure surface roughness and hardness respectively. Statistical data analysis was conducted via Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM, USA). The independent sample t-test was used and p ≤ 0.05 was considered statistically significant. RESULTS: The addition of henna at varying concentrations significantly increased the surface roughness values (p ≤ 0.01) while decreasing hardness (p ≤ 0.0001). The most favorable addition value was 1% henna between all henna groups. CONCLUSION: The addition of henna to the acrylic resin may negatively affect the surface properties of PMMA acrylic denture base. CLINICAL SIGNIFICANCE: Antimicrobial denture with minimum deterioration effects on its physical properties could be achieved with henna addition to denture base material in low concentration. However, 1% henna showed the best results between the henna groups as regards roughness and hardness values.


Asunto(s)
Bases para Dentadura , Lawsonia (Planta) , Preparaciones de Plantas/uso terapéutico , Polimetil Metacrilato/uso terapéutico , Relación Dosis-Respuesta a Droga , Dureza/efectos de los fármacos , Humanos , Técnicas In Vitro , Preparaciones de Plantas/administración & dosificación , Polimetil Metacrilato/química , Propiedades de Superficie/efectos de los fármacos
16.
Int J Nanomedicine ; 13(T-NANO 2014 Abstracts): 101-105, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29593406

RESUMEN

Curcuminoids (Curs), oleoresins from Curcuma longa L., have known anticarcinogenic and anti-inflammatory properties, but high toxicity, poor aqueous solubility and susceptibility to degradation in body fluids are deterrents to their clinical administration. Poly(methyl methacrylate) nanoparticles (PMMA-NPs) are biocompatible and resilient and can entrap hydrophobic drugs. The present investigation is related to solubilizing Curs by incorporating them in these nanoparticles (NPs) and is related to a study comparing the anticarcinogenic effect of drug-loaded NPs with free Cur using lung cancer (A549) cell line. Freshly extracted oleoresins were post loaded in PMMA-NPs prepared using emulsion polymerization. The presence of the three components of oleoresins was confirmed by thin-layer chromatography. The size and morphology of void and loaded NPs were determined by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. The NPs were spherical with diameters of 192.66±5 nm (void) and 199.16±5 nm (loaded). Drug loading and encapsulation efficiency were 6% and 93%, respectively. From the Fourier transform infrared spectroscopy spectra, the characteristic absorption vibration of poly(methyl methacrylate) and the bands at 1,383, 1,233 and 962 cm-1 for Cur moiety were observed. Drug release up to 10 days was estimated in buffer, saline and serum. The highest release of ~55% in ~3 days was noted in buffer that exhibited the highest bioavailability. The in vitro anticancer activity of loaded drug was evaluated up to 72 hours by MTT assay using A549 cell line. Cellular uptake of dye-loaded NPs was visualized within 30 minutes of incubation. The results revealed that the dose- and time-dependent cell death in case of loaded PMMA-NPs was comparable to that of free Cur. According to the study, the drug-loaded PMMA-NPs appear to be highly suitable for effective, localized and safe chemotherapy.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Curcumina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Polimetil Metacrilato/química , Células A549 , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Muerte Celular/efectos de los fármacos , Curcumina/análogos & derivados , Curcumina/química , Diarilheptanoides , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Liberación de Fármacos , Dispersión Dinámica de Luz , Emulsiones/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Microscopía Electrónica de Transmisión , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Polimerizacion , Espectroscopía Infrarroja por Transformada de Fourier
17.
J Mech Behav Biomed Mater ; 79: 246-253, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29335191

RESUMEN

In this study, alumina-reinforced poly(methyl methacrylate) nanocomposites (PMMA/Al2O3) containing up to 20vol% nanoparticles with an average diameter of 50nm were prepared by friction stir processing. The effects of nanoparticle volume fraction on the microstructural features and mechanical properties of PMMA were studied. It is shown that by using a frustum pin tool and employing an appropriate processing condition, i.e. a rotational speed of 1600rpm/min and transverse velocity of 120mm/min, defect free nanocomposites at microscale with fine distribution of the nanoparticles can successfully been prepared. Mechanical evaluations including tensile, flexural, hardness and impact tests indicate that the strength and toughness of the material gradually increases with the nanoparticle concentration and reach to a flexural strength of 129MPa, hardness of 101 Shore D, and impact energy 2kJ/m2 for the nanocomposite containing 20vol% alumina. These values are about 10% and 20% better than untreated and FSP-treated PMMA (without alumina addition). Fractographic studies indicate typical brittle features with crack deflection around the nanoparticles. More interestingly, the sliding wear rate in a pin-on-disk configuration and the friction coefficient are reduced up to 50% by addition of alumina nanoparticles. The worn surfaces exhibit typical sliding and ploughing features.


Asunto(s)
Óxido de Aluminio/química , Materiales Biocompatibles/química , Nanopartículas del Metal/química , Nanocompuestos/química , Fricción , Dureza , Ensayo de Materiales , Polimetil Metacrilato/química , Propiedades de Superficie
18.
Tissue Eng Part A ; 24(9-10): 703-710, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28851250

RESUMEN

INTRODUCTION: Standard care for malignant tumors arising next to a bone structure is surgical removal with safety margins, followed by external beam radiotherapy (EBRT). Complete tumor removal can result in large bone defects. A two-step bone reconstruction technique using the induced membrane (IM) technique has proven its efficacy to bridge gap nonunion. During the first step, a spacer is placed in the bone gap. The spacer then is removed and the IM around it is filled with autologous cancellous bone graft. However, the feasibility of this technique with the addition of adjuvant EBRT between the two reconstruction steps has not yet been studied. Polymethyl methacrylate (PMMA) used to be the standard spacer material for the first step. Silicone spacers could replace them owing to their good behavior when submitted to EBRT and their easier removal from the surgical site during the second step. The aim of this study was to evaluate the influence of EBRT on the histological and biochemical properties of IM induced using PMMA or silicone as spacer. MATERIALS AND METHODS: The analyses were performed on PMMA- or silicone-IM with and without EBRT in a 6-mm bilateral femoral defect in 32 rats. Thickness and vessel content were measured in both groups. Bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) content in lysates of the crushed membranes were measured by enzyme immunoassay. Finally, alkaline phosphatase activity was analyzed in human bone marrow stromal cell cultures in contact with the same lysates. RESULTS: EBRT did not change the histological structure of the cellular internal layer or the fibrous outer layer. The nature of the spacer only influenced IM thickness, PMMA-IM with external radiotherapy being significantly thicker. EBRT decreased the vascular density of IM but was less effective on VEGF/BMP2 production. In vitro, IM could have an osteoinductive potential on human bone marrow stem cells. CONCLUSION: EBRT did not modify the histological properties of IMs but decreased their vascular density. VEGF and BMP2 production within IMs was not affected by EBRT. Silicone spacers are able to induce membranes with similar histological characteristics to PMMA-IM.


Asunto(s)
Huesos/metabolismo , Huesos/patología , Polimetil Metacrilato/química , Siliconas/química , Animales , Proteína Morfogenética Ósea 2/metabolismo , Línea Celular , Femenino , Humanos , Inmunohistoquímica , Cuidados Posoperatorios , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo
19.
Biotechnol Bioeng ; 115(4): 1086-1095, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29280498

RESUMEN

Scaffold based systems have shown significant potential in modulating immune responses in vivo. While there has been much attention on macrophage interactions with tissue engineered scaffolds for tissue regeneration, fewer studies have looked at the effects of scaffold design on the response of immune cells-that is, dendritic cells (DCs). Here, we present the effects of varying pore size of poly (2-hydroxyethyl methacrylate) (pHEMA) and poly(dimethylsiloxane) (PDMS, silicone) scaffolds on the maturation and in vivo enrichment of DCs. We employ a precision templating method to make 3-D porous polymer scaffolds with uniformly defined and adjustable architecture. Hydrophilic pHEMA and hydrophobic PDMS scaffolds were fabricated in three pore sizes (20, 40, 90 µm) to quantify scaffold pore size effects on DCs activation/maturation in vitro and in vivo. In vitro results showed that both pHEMA and PDMS scaffolds could promote maturation in the DC cell line, JAWSII, that resembled lipopolysaccharide (LPS)-activated/matured DCs (mDCs). Scaffolds with smaller pore sizes correlate with higher DC maturation, regardless of the polymer used. In vivo, when implanted subcutaneously in C57BL/6J mice, scaffolds with smaller pore sizes also demonstrated more DCs recruitment and more sustained activation. Without the use of DC chemo-attractants or chemical adjuvants, our results suggested that DC maturation and scaffold infiltration profile can be modulated by simply altering the pore size of the scaffolds.


Asunto(s)
Células Dendríticas/efectos de los fármacos , Andamios del Tejido/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Dendríticas/química , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Lipopolisacáridos/farmacología , Metacrilatos/química , Metacrilatos/farmacología , Ratones , Ratones Endogámicos C57BL , Microesferas , Nylons/química , Nylons/farmacología , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacología , Porosidad
20.
Int J Nanomedicine ; 12: 8363-8373, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29200848

RESUMEN

This study aimed to synthesize and characterize nanoparticles (NPs) of poly(methyl methacrylate) (PMMA) and evaluate their ability to incorporate plant extracts with antitumor activity and low dissolution in aqueous media. The extract used was n-hexane partition of the methanol extract of Piper cabralanum (PCA-HEX). PMMA NPs were obtained using the mini-emulsion method, which was able to encapsulate almost 100% of PCA-HEX. The synthesized polymeric particles presented with a size of 200 nm and a negative charge. Cytotoxicity tests by MTT and trypan blue assays showed that NPs without PCA-HEX did not kill leukemic cells (K562 cells). NPs containing PCA-HEX were able to enhance cell death when compared to pure extract. The results showed that PMMA NPs could be useful as a drug delivery system as they can enhance the antitumor activity of the PCA-HEX extract by more than 20-fold. PMMA NPs containing plant extracts with antitumor activities may be an alternative to control the evolution of diseases such as leukemia.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Nanopartículas/química , Piper/química , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Muerte Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Emulsiones/administración & dosificación , Hexanos/química , Humanos , Células K562 , Nanopartículas/administración & dosificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Polimetil Metacrilato/química
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