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Additive manufacturing (AM) is changing our current approach to the clinical treatment of bone diseases, providing new opportunities to fabricate customized, complex 3D structures with bioactive materials. Among several AM techniques, the BioCell Printing is an advanced, integrated system for material manufacture, sterilization, direct cell seeding and growth, which allows for the production of high-resolution micro-architectures. This work proposes the use of the BioCell Printing to fabricate polymer-based scaffolds reinforced with ceramics and loaded with bisphosphonates for the treatment of osteoporotic bone fractures. In particular, biodegradable poly(ε-caprolactone) was blended with hydroxyapatite particles and clodronate, a bisphosphonate with known efficacy against several bone diseases. The scaffolds' morphology was investigated by means of Scanning Electron Microscopy (SEM) and micro-Computed Tomography (micro-CT) while Energy Dispersive X-ray Spectroscopy (EDX) and X-ray Photoelectron Spectroscopy (XPS) revealed the scaffolds' elemental composition. A thermal characterization of the composites was accomplished by Thermogravimetric analyses (TGA). The mechanical performance of printed scaffolds was investigated under static compression and compared against that of native human bone. The designed 3D scaffolds promoted the attachment and proliferation of human MSCs. In addition, the presence of clodronate supported cell differentiation, as demonstrated by the normalized alkaline phosphatase activity. The obtained results show that the BioCell Printing can easily be employed to generate 3D constructs with pre-defined internal/external shapes capable of acting as a temporary physical template for regeneration of cancellous bone tissues.
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Poly (Lactic Acid), PLA, and Poly (ε-CaproLactone), PCL, compatibilized with Ethyl Ester l-Lysine Triisocyanate (LTI) can be employed as biomaterials. We mixed PLA with PCL and LTI in a twin extruder and by a melt spinning process obtained threads with an average diameter of about 0.3 mm. In order to study the possible application of these threads, mechanical tensile (with the calorimetric and morphological investigations) and biological tests were performed. The results highlighted these biopolymers as promising materials for sutures since they can be rigid and elastic (especially by increasing the PCL amount in the blend), and they are bioactive, able to inhibit bacterial growth. This paper represents a starting point to optimize the blend composition for biomedical suture application.
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Implanted biomedical devices can induce adverse responses in the human body, which can cause failure of the implant-referred to as implant failure. Early implant failure is induced numerous factors, most importantly, infection and inflammation. Natural products are, today, one of the main sources of new drug molecules due to the development of pathogenic bacterial strains that possess resistance to more antibiotics used currently in various diseases. The aim of this work is the solâ»gel synthesis of antibacterial biomedical implants. In the silica matrix, different percentages (6, 12, 24, 50 wt %) of polyethylene glycol (PEG) or poly(ε-caprolactone) (PCL) were embedded. Subsequently, the ethanol solutions with high amounts of chlorogenic acid (CGA 20 wt %) were slowly added to SiO2/PEG and SiO2/PCL sol. The interactions among different organic and inorganic phases in the hybrid materials was studied by Fourier transform infrared (FTIR) spectroscopy. Furthermore, the materials were soaked in simulated body fluid (SBF) for 21 days and the formation of a hydroxyapatite layer on their surface was evaluated by FTIR and XRD analysis. Finally, Escherichia coli and Pseudomonas aeruginosa were incubated with several hybrids, and the diameter of zone of inhibition was observed to assessment the potential antibacterial properties of the hybrids.
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The diversity in phenols and polyphenols of stevia leaf has been simplified applying sequential fractionation techniques on its ethanol extract through ultrasound assisted maceration. Two of the fractions obtained by reverse-phase column chromatography resulted differently active in an extensive antioxidant and cytotoxic screening. Both fractions were chemically profiled by ultra-performance liquid chromatography (UHPLC) coupled with electrospray ionization (ESI) quadrupole/time-of-flight (QqTOF) mass spectrometry (MS). One of the fractions was composed mainly of chlorogenic acids and flavonol triglycosides, whereas the other was rich in flavonoids mono- and diglycosides and in their hydroxycinnamoyl derivatives. Among the fifty compounds identified, non-phenol metabolites, such as benzyl primeveroside and roseoside, as well as a lignan polyphenol (5'), are reported for the first time as constituents of the Stevia leaf.
Assuntos
Fracionamento Químico/métodos , Fenóis/análise , Extratos Vegetais/química , Stevia/química , Células 3T3 , Animais , Antineoplásicos/análise , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Fracionamento Químico/instrumentação , Ácido Clorogênico/análise , Ácido Clorogênico/química , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Glicosídeos/análise , Glicosídeos/química , Humanos , Camundongos , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/instrumentação , Espectrometria de Massas em Tandem/métodosRESUMO
Titanium biomaterials' response has been recognized to be affected by particles size, crystal structure, and surface properties. Chemical and structural properties of these nanoparticle materials are important, but their size is the key aspect. The aim of this study is the synthesis of TiO2 nanoparticles by the sol-gel method, which is an ideal technique to prepare nanomaterials at low temperature. The heat treatment can affect the structure of the final product and consequently its biological properties. For this reason, the chemical structure of the TiO2 nanoparticles synthesized was investigated after each heat treatment, in order to evaluate the presence of different phases formed among the nanoparticles. FTIR spectroscopy and XRD have been used to evaluate the different structures. The results of these analyses suggest that an increase of the calcination temperature induces the formation of mixed-crystalline-phases with different content of anatase and rutile phases. The results obtained by SEM measurements suggest that an increase in the particles size accompanied by a noticeable aggregation of TiO2 nanoparticles is due to high temperatures achieved during the thermal treatments and confirmed the presence of different content of the two crystalline phases of titanium dioxide.
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The use of oral iron integration is commonly recommended for the treatment of iron deficiency, nevertheless the diagnosis and treatment of this disease could clearly be improved. The aim of this work was the synthesis of therapeutic systems, iron (II) based, by sol-gel method. In an SiO2 matrix, we embedded different weight percentages of polyethylene glycol (PEG6, 12, 24 wt%) and ferrous citrate (Fe(II)C5, 10, 15 wt%) for drug delivery applications. Fourier Transform Infrared (FTIR) spectroscopy was used to study the interactions among different components in the hybrid materials. Release kinetics in a simulated body fluid (SBF) were investigated and the amount of Fe2+ released was detected by Ultravioletâ»Visible spectroscopy (UV-VIS) after reaction with ortho-phenantroline. Furthermore, the biological characterization was carried out. The bioactivity of the synthesized hybrid materials was evaluated by the formation of a layer of hydroxyapatite on the surface of samples soaked in SBF using FTIR spectroscopy. Finally, also, the potential antibacterial properties of the different materials against two different bacteria, E. coli and P. aeruginosa, were investigated.
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Chlorogenic acid (CGA) is a very common dietary polyphenolic compound. CGA is becoming very attractive due to its potential use as preventive and therapeutic agent in many diseases, including cancer. Inorganic/organic hybrid materials are gaining considerable attention in the biomedical field. The sol-gel process provides a useful way to obtain functional organic/inorganic hybrids. The aim of this study was to synthesize silica/polyethylene glycol (PEG) hybrids with different percentages of CGA by sol-gel technique and to investigate their impact on the cancer cell proliferation. Synthesized materials have been chemically characterized through the FTIR spectroscopy and their bioactivity evaluated looking by SEM at their ability to produce a hydroxyapatite layer on their surface upon incubation with simulated body fluid (SBF). Finally, their effects on cell proliferation were studied in cell lines by direct cell number counting, MTT, flow cytometry-based cell-cycle and cell death assays, and immunoblotting experiments. Notably, we found that SiO2/PEG/CGA hybrids exhibit clear antiproliferative effects in different tumor, including breast cancer and osteosarcoma, cell lines in a CGA dependent manner, but not in normal cells. Overall, our results increase the evidence of CGA as a possible anticancer agent and illustrate the potential for clinical applications of sol-gel synthesized SiO2/PEG/CGA materials.
Assuntos
Ácido Clorogênico/química , Polietilenoglicóis/química , Dióxido de Silício/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Técnicas de Química Sintética/métodos , Ácido Clorogênico/síntese química , Durapatita/química , Humanos , Teste de Materiais , Transição de Fase , Polietilenoglicóis/síntese química , Dióxido de Silício/síntese químicaRESUMO
In this work, new phenol-based materials have been synthesized by the sol-gel method, in which different amounts of the phenolic antioxidant chlorogenic acid (CGA) (from 5 wt % to 20 wt %) were embedded in two different silica matrices: pure silica and silica-based hybrids materials, containing 50 wt % of polyethylene glycol (PEG). The incorporation of CGA in different sol-gel matrices might protect them from degradation, which could cause the loss of their properties. The two series of materials were chemically characterized by Fourier transform infrared (FTIR) spectroscopy. In addition, the thermal behavior of both series of materials containing CGA was studied by thermogravimetry under both air and inert N2 flowing gas atmosphere. The bioactivity was evaluated by soaking the synthesized hybrids in a simulated body fluid, showing that the bioactivity of the silica matrix is not modified by the presence of PEG and CGA.
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Organic/inorganic hybrid materials are attracting considerable attention in the biomedical area. The sol-gel process provides a convenient way to produce many bioactive organic-inorganic hybrids. Among those, poly(e-caprolactone)/zirconia (PCL/ZrO2) hybrids have proved to be bioactive with no toxic materials. The aim of this study was to investigate the effects of these materials on the cellular response as a function of the PCL content, in order to evaluate their potential use in the biomedical field. For this purpose, PCL/ZrO2 hybrids containing 6, 12, 24, and 50 wt % of PCL were synthesized by the sol-gel method. The effects of their presence on the NIH-3T3 fibroblast cell line carrying out direct cell number counting, MTT, cell damage assays, flow cytometry-based analysis of cell-cycle progression, and immunoblotting experiments. The results confirm and extend the findings that PCL/ZrO2 hybrids are free from toxicity. The hybrids containing 12 and 24 wt % PCL, (more than 6 and 50 wt % ones) enhance cell proliferation when compared to pure ZrO2 by affecting cell cycle progression. The finding that the content of PCL in PCL/ZrO2 hybrids differently supports cell proliferation suggests that PCL/ZrO2 hybrids could be useful tools with different potential clinical applications.
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Zirconia (ZrO2) and zirconia-based glasses and ceramics are materials proposed for use in the dental and orthopedic fields. In this work, ZrO2 glass was modified by adding different amounts of bioactive and biocompatible hydroxyapatite (HAp). ZrO2/HAp composites were synthesized via the sol-gel method and heated to different temperatures to induce modifications of their chemical structure, as ascertained by Fourier transform infrared spectroscopy (FTIR) analysis. The aim was to investigate the effect of both HAp content and heating on the biological performances of ZrO2. The materials' bioactivity was studied by soaking samples in a simulated body fluid (SBF). FTIR and scanning electron microscopy (SEM)) analyses carried out after exposure to SBF showed that all materials are bioactive, i.e., they are able to form a hydroxyapatite layer on their surface. Moreover, the samples were soaked in a solution containing bovine serum albumin (BSA). FTIR analysis proved that the synthesized materials are able to adsorb the blood protein, the first step of cell adhesion. WST-8 ([2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt]) assay showed that no cytotoxicity effects were induced by the materials' extract. However, the results proved that bioactivity increases with both the HAp content and the temperature used for the thermal treatment, whereas biocompatibility increases with heating but is not affected by the HAp content.