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BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. METHODS: The OSCC cells were treated with varying concentrations and duration of ALT and N-Acetyl-L-cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. RESULTS: ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. CONCLUSIONS: ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.
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Dinaminas , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Trifosfato de Adenosina/metabolismo , Apoptose , Linhagem Celular Tumoral , Regulação para Baixo , Dinaminas/metabolismo , Dinaminas/farmacologia , Dinaminas/uso terapêutico , Mitocôndrias/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Fiber post bonding failure remains an issue during crown restoration procedures. This experiment examines the bonding effect of combined Er:YAG laser treatment on both root canal and fiber post. Sixty extracted mandibular first premolars were randomly selected and divided into 6 groups (n = 10 per group): G1 (control group): root canal with 2.5% NaClO treatment, no treatment of fiber post; G2: root canal with 2.5% NaClO treatment and fiber post with airborne-particle abrasion; G3: root canal with Er:YAG laser treatment and fiber post with airborne-particle abrasion; G4: root canal with Er:YAG laser treatment, no treatment of fiber post; G5: root canal with 2.5% NaClO treatment, fiber post with Er:YAG laser irradiation; G6: combined Er:YAG laser irradiation of both root canal and fiber post. An Er:YAG laser with a wavelength of 2940 nm was used to treat the fiber post (4.5 W, 450 mJ, 10 Hz for 60 s at 100-µs pulse duration with 100% water cooling) and the root canal (1.5 W, 150 mJ, 10 Hz for 60 s at 100-µs pulse duration with 100% water cooling). When the root canal was treated with the laser, the fiber tip was inserted into the root canal to make a spiral reciprocating motion. Bond strength was analyzed by a micro push-out test. Data were analyzed using both the Tukey test and two-way ANOVA (α = 0.05). Failure modes were observed and counted through a stereo microscope. The root canal and fiber post surface analysis was performed using SEM. The bond strength of G3 and G6 were significantly enhanced compared to those of the other groups (p < 0.05). The SEM analysis showed that the smear layers of groups with root canals subjected to Er:YAG laser irradiation were significantly reduced compared to those of the control group (G1). In groups with fiber posts treated with Er:YAG laser irradiation, the surfaces of the fiber posts exhibited greater surface roughness and a certain degree of epoxy matrix removal. Through the combined Er:YAG laser irradiation of both root canal and fiber post, the bond strength between them was significantly enhanced, which was superior to the individual treatment of either fiber posts or root canal.
Assuntos
Colagem Dentária , Lasers de Estado Sólido , Técnica para Retentor Intrarradicular , Lasers de Estado Sólido/uso terapêutico , Cavidade Pulpar , Tratamento do Canal Radicular , Resinas Epóxi , Dentina/efeitos da radiaçãoRESUMO
BACKGROUND Ideal bone repair material should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to those of natural bone. The objective of this study was to fabricate a novel biocomposite suitable for load-bearing bone defect repair. MATERIAL AND METHODS A novel biocomposite composed of carbon fiber, hydroxyapatite and polyamide46 (CF/HA/PA46) was fabricated, and its mechanical performances and preliminary cell responses were evaluated to explore its feasibility for load-bearing bone defect repair. RESULTS The resultant CF/HA/PA46 biocomposite showed a bending strength of 159-223 MPa, a tensile strength of 127-199 MPa and a tensile modulus of 7.7-10.8 GPa, when the CF content was 5-20% (mass fraction) in biocomposite. The MG63 cells, showing an osteogenic phenotype, were well adhered and spread on the surface of the CF/HA/PA46 biocomposite. Moreover, the cells vitality and differentiation on the CF/HA/PA46 biocomposite surface were obviously increased during the culture time and there was no significant difference between the CF/HA/PA46 biocomposite and HA/PA (as control) at all the experimental time (P>0.05). CONCLUSIONS The addition of CF into HA/PA46 composite manifest improved the mechanical performances and showed favorable effects on biocompatibility of MG63 cells. The obtained biocomposite has high potential for bone repair in load-bearing sites.
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Materiais Biocompatíveis/química , Substitutos Ósseos/farmacologia , Carbono/química , Durapatita/química , Nanopartículas/química , Nylons/farmacologia , Engenharia Tecidual/métodos , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Fibra de Carbono , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Nanopartículas/ultraestrutura , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BuChE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (Aß) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8 nM, potent inhibition of self-induced Aß1-42 aggregation with inhibition ratio of 33.8% at 25 µM. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD.
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Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Flavonas/farmacologia , Tacrina/análogos & derivados , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/síntese química , Antioxidantes/química , Butirilcolinesterase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Electrophorus , Equidae , Flavonas/síntese química , Flavonas/química , Estrutura Molecular , Células PC12 , Ratos , Relação Estrutura-Atividade , Tacrina/síntese química , Tacrina/química , Tacrina/farmacologiaRESUMO
Titanium is widely used in biomedical materials, particularly in dental implants, because of its excellent biocompatibility and mechanical characteristics. However, titanium implant failures still remain in some cases, varying with implantation sites and patients. Improving its overall performance is a major focus of dental implant research. Equal-channel angular pressing (ECAP) can result in ultrafine-grained titanium with superior mechanical properties and better biocompatibility, which significantly benefits dental implants, and without any harmful alloying elements. Lanthanum (La) can inhibit the acidogenicity of dental plaque and La-containing hydroxyapatite (La-HA) possesses a series of attractive properties, in contrast to La-free HA. Micro-arc oxidation (MAO) is a promising technology that can produce porous and firmly adherent hydroxyapatite (HA) coatings on titanium substrates. Therefore, we hypothesize that porous La-containing hydroxyapatite coatings with different La content (0.89%, 1.3% and 1.79%) can be prepared on ultrafine-grained (~200-400 nm) titanium by ECAP and MAO in electrolytic solution containing 0.2 mol/L calcium acetate, 0.02 mol/L beta-glycerol phosphate disodium salt pentahydrate (beta-GP), and lanthanum nitrate with different concentrations to further improve the overall performance of titanium, which are expected to have great potential in medical applications as a dental implant.
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Materiais Biocompatíveis/química , Implantes Dentários , Durapatita/química , Lantânio/química , Titânio/química , Titânio/normas , Durapatita/análise , Humanos , Teste de Materiais , Oxirredução , Porosidade , Propriedades de Superfície , Titânio/uso terapêuticoRESUMO
Degradation profiles are critical for the optimal application of electrospun polymer nanofibers in tissue regeneration, wound healing, and drug delivery systems. In this study, natural and synthetic polymers and their composites were subjected to in vivo transplantation and in vitro treatment with lipases, macrophages, and acetic acid to evaluate their degradation patterns. The effects of environmental stimulation, surface wettability, and polymer components on the degradation profiles of the electrospinning poly(ε-caprolactone)/silk fibroin (PCL/SF) nanofibers were first evaluated. In vivo degradation study demonstrated that bulk degradation, characterized by the transition from microfibers to nanofibers, and surface erosion, characterized by fusion between the microfibers or direct erosion from both ends of the microfibers, occurred in the electrospun membranes; however, bulk degradation dominated their overall degradation. Furthermore, the degradation rates of the electrospun PCL/SF membranes varied according to the composition, morphology, and surface wettability of the composite membranes. After the incorporation of silk fibroin (SF), the degradation rate of the SF/PCL composite membranes was faster, accompanied by larger values of weight loss and molecular weight (Mw) loss when compared with that of the pure poly(ε-caprolactone) (PCL) membrane, indicating a close relationship between degradation rate and hydrophilicity of the electrospinning membranes. The in vitro experimental results demonstrated that enzymes and oxidation partially resulted in the surface erosion of the PCL/SF microfibers. Consequently, bulk degradation and surface erosion coordinated with each other to enhance the hydrophilicity of the electrospinning membranes and accelerate the in vivo degradation.
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Fibroínas , Poliésteres , Engenharia Tecidual , Fibroínas/química , Poliésteres/química , Engenharia Tecidual/métodos , Animais , Nanofibras/química , Membranas Artificiais , Camundongos , Molhabilidade , Alicerces Teciduais/química , Materiais Biocompatíveis/químicaRESUMO
Zwitterionic polymers have attracted considerable attention because of their anti-adsorption and unique anti-polyelectrolyte effects and was widely used in surface modification. In this study, zwitterionic copolymers (poly (sulfobetaine methacrylate-co-butyl acrylate) (pSB) coating on the surface of a hydroxylated titanium sheet using surface-initiated atom transfer radical polymerization (SI-ATRP) was successfully constructed. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Water contact angle (WCA) analysis proved the successful preparation of the coating. The swelling effect caused by the anti-polyelectrolyte effect was reflected in the simulation experiment in vitro, and this coating can promote the proliferation and osteogenesis of MC3T3-E1. Therefore, this study provides a new strategy for designing multifunctional biomaterials for implant surface modifications.
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Polímeros , Titânio , Polímeros/farmacologia , Polímeros/química , Titânio/farmacologia , Polieletrólitos/farmacologia , Osteogênese , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de SuperfícieRESUMO
OBJECTIVES: This study aims to investigate the cytotoxicity and sustainable antibacterial activity of unmodified PEEK under specific wavelength light treatment (365 nm), and its antibacterial mechanism was also preliminarily discussed. METHODS: A near-ultraviolet source with a wavelength of 365 nm and a power of 5 W were selected. The irradiation time was 30 min, and the distance was 100 mm. A water contact angle tester was used to characterize the surface of the PEEK after 1-15 light treatments. MC3TC-E1 cells were used to evaluate the cytotoxicity of the materials under light treatment. Five kinds of common oral bacteria were detected in vitro, and antibacterial efficiency was determined by colony-forming unit (CFU) and scanning electron microscope (SEM). The antibacterial mechanism of PEEK under light was preliminarily discussed by spectrophotometry. The membrane rupture of Staphylococcus aureus and Escherichia coli was detected by lactate dehydrogenase. Staphylococcus aureus and Staphylococcus mutans were selected for the cyclic antibacterial test. Statistical analysis was performed by one-way analysis of variance and Tukey multiple range test. A significance level of 0.05 was considered (α = 0.05). RESULTS: The results of the cell experiment showed that PEEK had no cytotoxicity (P > 0.05). CFU results showed that PEEK had an obvious antibacterial effect on Staphylococcus aureus, Staphylococcus mutans, Staphylococcus gordonii and Staphylococcus sanguis, but had no antibacterial effect on Escherichia coli (P < 0.05). The SEM results also verified the above antibacterial effect. The existence of singlet oxygen was confirmed by spectrophotometry. Meanwhile, the rupture of Staphylococcus aureus membrane was verified by lactate dehydrogenase assay. The water contact angle of the PEEK surface did not change significantly after 15 cycles of light treatment. Cyclic antibacterial experiments showed that the antibacterial effect was sustainable. CONCLUSIONS: This study showed that PEEK has good cytocompatibility with stable and sustainable antibacterial properties under near-ultraviolet. It provides a new idea to solve the non-antibacterial property of PEEK, and also provides a theoretical basis for its further application in dentistry.
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Cetonas , Polietilenoglicóis , Polietilenoglicóis/farmacologia , Cetonas/farmacologia , Benzofenonas/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , Escherichia coli , Água , Lactato Desidrogenases , ÉteresRESUMO
The accelerating bone healing process is still a major challenge in clinical orthopedics, especially in critical-sized bone defects. Recently, Nanofiber membranes are showing increasing attention in the biomedical field due to their good biocompatibility, mechanical stability, and the ability to work as a drug carrier to achieve localized and sustained drug delivery. Herein, a multifunction nanofiber membrane loaded with vitamin D (Vit D) and curcumin (Cur) was successfully fabricated using electrospinning technology. In addition, we innovatively modified Vit D with PEG to improve the hydrophilicity of PCL nanofibers. The vitro results of CCK-8, alkaline phosphatase (ALP) and mineralization demonstrated that the PCL/Vit D-Cur membrane had great potential for enhancing the proliferation/differentiation of osteoblasts. Moreover, the synergistic effect of Vit D-Cur loaded PCL nanofiber membrane showed a superior ability to improve the anti-inflammatory activity through M2 polarization. Furthermore, in vivo results confirmed that the defect treated with PCL/Vit D-Cur nanofiber membrane was filled with the newly formed bone after 1 month. These results indicate that the Vit D/Cur loaded membrane can be applied for potential bone regeneration therapy.
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The excessive accumulation of reactive oxygen species (ROS) under osteoporosis precipitates a microenvironment with high levels of oxidative stress (OS). This could significantly interfere with the bioactivity of conventional titanium implants, impeding their early osseointegration with bone. We have prepared a series of strontium (Sr)-doped titanium implants via micro-arc oxidation (MAO) to verify their efficacy and differences in osteoinduction capabilities under normal and osteoporotic (high OS levels) conditions. Apart from the chemical composition, all groups exhibited similar physicochemical properties (morphology, roughness, crystal structure, and wettability). Among the groups, the low Sr group (Sr25%) was more conducive to osteogenesis under normal conditions. In contrast, by increasing the catalase (CAT)/superoxide dismutase (SOD) activity and decreasing ROS levels, the high Sr-doped samples (Sr75% and Sr100%) were superior to Sr25% in inducing osteogenic differentiation of MC3T3-E1 cells and the M2 phenotype polarization of RAW264.7 cells, thus enhancing early osseointegration. Furthermore, the results of both in vitro cell co-culture and in vivo studies also showed that the high Sr-doped samples (especially Sr100%) had positive effects on osteoimmunomodulation under the OS microenvironment. Ultimately, the collated findings indicated that the high proportion Sr-doped MAO coatings were more favorable for osteoporosis patients in implant restorations.
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Equipped with anti-oxidative properties, cerium oxide nanoparticles (CNPs) are gradually being adopted over the years in the field of oxidative stress research. However, the effects of CNPs may be diminished when under the influence of prolonged and substantially elevated levels of oxidative stress. Therefore, it is imperative to enhance the efficacy of CNPs to resist oxidative stress. In this study, our approach involves the fabrication of titanium surface CNPs coatings doped with different concentrations of lanthanum ions (La3+) and the investigation of their local anti-oxidative stress potential. The physicochemical characterization showed that the La-CNPs groups had a substantial increase in the generation of oxygen vacancies within the CNPs structure with the increase of La doping concentration. In vitro findings proofed that the cytocompatibility of different La-CNPs coatings showed a trend of increasing first and then decreasing with the increase of La doping concentration under oxidative stress microenvironment. Among these groups, the 30 % La-CNPs group presented the best cell proliferation and osteogenic differentiation which could activate the FoxO1 pathway, then upregulated the expression of SOD1 and CAT, and finally resulted in the inhibition of ROS production. In vivo results further confirmed that the 30 % La-CNPs group showed significant osteogenic effects in two rat models (osteoporosis and diabetes models). In conclusion, we believe that the 30 % La-CNPs coating holds promising potential for its implant applications in patients with oxidative stress-related diseases.
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Cério , Implantes Dentários , Nanopartículas , Animais , Cério/química , Cério/farmacologia , Lantânio/farmacologia , Nanopartículas/química , Osteogênese , Ratos , Espécies Reativas de Oxigênio/metabolismo , Titânio/farmacologiaRESUMO
Excessive accumulation of oxidative intermediates in the elderly significantly aggravates bone degradation and hinders the osseointegration of topological titanium (Ti) implants. Thus, it is of great significance to evaluate the antioxidant and osteoinduction capabilities of various nano, micro or micro/nano-composite structures under oxidative stress (OS) microenvironment. In this study, we discovered that 110 nm titania nanotubes (TNTs) enhanced the adsorption of fibronectin (FN) proteins onto smooth and rough titanium surfaces to varying degrees. Compared with Ti and 30 nm TNTs (T30) groups, cells on 110 nm TNTs (T110), microstructure/30 nm TNTs (M30) and microstructure/110 nm TNTs (M110) had smaller area, lower reactive oxygen species (ROS), and better proliferation/osteogenic differentiation abilities under OS condition, but there was no significant difference among the three groups. In addition, combined with our previous study, we suggested that T110, M30 and M110 resistance to OS was also strongly associated with the high expression of FN-receptor integrin α5 or ß1. All the findings indicated that the micro/nano-composed structures (M30 & M110) had similar anti-oxidation and osteogenesis abilities to T110, which provided guidance for the application of different titanium implants with different topologies in the elderly.
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Osteogênese , Titânio , Adesão Celular , Osteoblastos , Estresse Oxidativo , Propriedades de Superfície , Titânio/farmacologiaRESUMO
In this study, multifunctional tantalum copper composite nanotubes (TaCu-NTs) were coated on titanium for enhanced bacteriostatic, angiogenic and osteogenic properties. Three coatings of Ta, TaCu1 (Ta: Cu = 4:1 at.%), and TaCu2 (Ta: Cu = 1:1 at.%) were deposited on titanium by magnetron sputtering. The bare titanium and the three coatings were subsequently anodized into four kinds of nanotubes (NT) of TNT, Ta-NT, TaCu1-NT, and TaCu2-NT, respectively. The released copper ions measured by inductively coupled plasma atomic emission spectroscopy (ICP/AES) presented that TaCu2-NT coating released the highest amount of copper ions, which led to the best bacteriostasis against Escherichia coli and Staphylococcus aureus. Potentiodynamic polarization tests clarified that Ta-NT showed the highest corrosion resistance, followed by TaCu1-NT and TaCu2-NT. TaCu2-NT showed not only the best angiogenic property in terms of cell migration, tube formation, and real-time quantitative polymerase chain reaction (RT-qPCR) of human umbilical vein endothelial cells (HUVECs), but also the best osteogenic property in terms of cell viability, alkaline phosphatase activity, and mineralization of MC3T3-E1 cells. Therefore, TaCu2-NT coating has a greater potential than the other coatings of TNT, Ta-NT and TaCu1-NT in promoting bacteriostasis, angiogenesis and osteointegration for titanium implants.
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Nanotubos , Titânio , Materiais Revestidos Biocompatíveis/farmacologia , Corrosão , Humanos , Osteogênese , Propriedades de Superfície , Tantálio , Titânio/farmacologiaRESUMO
Antibacterial and osteogenic functionalization of titanium (Ti) implants will greatly expand their clinical indications in immediate implant therapy, accelerate osteointegration, and enhance long-term prognosis. We had recently shown that the high-energy shot peening (HESP)-assisted micro-arc oxidation (MAO) significantly improved the bioactivity and coating stability of Ti-based substrates. In this study, we further functionalized Ti with antibacterial and osteogenic properties by doping silicon (Si) and/or copper (Cu) ions into HESP/MAO-treated coatings. Physicochemical characterization displayed that the doping of Si and Cu in HESP/MAO-treated coatings (Si/Cu-MAO) did not significantly change their surface topography, roughness, crystal structure, coating thickness, bonding strength, and wettability. The results of X-ray photoelectron spectroscopy (XPS) showed that Si and Cu in the Si/Cu-MAO coating was in the form of silicate radical (SiO3 2-) and bivalent copper (Cu2+), respectively. The total amounts of Si and Cu were about 13.5 and 5.8 µg/cm2, which released about 33.2 and 31.3% within 14 day, respectively. Compared with the control group (MAO), Si doping samples (MAO-Si) significantly increased the cell viability, alkaline phosphatase (ALP) activity, mineralization and osteogenic genes (ALP, collagen I and osteocalcin) expression of MC3T3-E1 cells. Furthermore, the addition of Cu presented good bactericidal property against both Staphylococcus aureus and Streptococcus mutans (even under the co-culture condition of bacteria and MC3T3-E1 cells): the bacteriostatic rate of both bacteria was over 95%. In conclusion, the novel bioactive Si/Cu-MAO coating with antibacterial and osteogenic properties is a promising functionalization method for orthopedic and dental implants, especially in the immediate implant treatment with an infected socket.
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Background: Although titanium dioxide nanotubes (TNTs) had great potential to promote osteogenesis, their weak bonding strength with titanium substrates greatly limited their clinical application. Purpose: The objective of this study was to maintain porosity and improve the stability of TNT coatings by preparing some micro-patterned mesoporous/nanotube (MP/TNT) structures via a photolithography-assisted anodization technology. Methods: The adhesion strength of different coatings was studied by ultrasonic cleaning machine and scratch tester. The early adhesion, spreading, proliferation and differentiation of MC3T3-E1 cells on different substrates were investigated in vitro by fluorescent staining, CCK8, alkaline phosphatase activity, mineralization and polymerase chain reaction assays, respectively. Results: Results of ultrasonic and scratch assays showed that the stability of TNTs (especially 125 nm) was significantly improved after being patterned with MP structures. In vitro cell assays further demonstrated that the insertion of MP structure into 125 nm TNT coating, which was denoted as MP125, could effectively improve the early adhesion, spreading and proliferation of surface MC3T3-E1 cells without damaging their osteogenic differentiation. Conclusion: We determined that the MP/TNT patterned samples (especially MP125) have excellent stability and osteogenesis properties, and may have better clinical application prospects.
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Nanotubos/química , Osteogênese , Titânio/química , Adsorção , Fosfatase Alcalina/metabolismo , Animais , Adesão Celular/genética , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/genética , Forma Celular/genética , Sobrevivência Celular/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fluorescência , Regulação da Expressão Gênica , Humanos , Camundongos , Minerais/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , Porosidade , Água/químicaRESUMO
OBJECTIVE: The aim of this study was to explore the mutual communication of the parathyroid hormone-related peptide (PTHrP) and phosphatidylinositol 3-kinase/threonine protein kinase (PI3K/Akt) pathway on the proliferation and differentiation of condylar chondrocytes from Sprague-Dawley (SD) rats. METHODS: Condylar chondrocytes from the condylar cartilage were cultured and an organ culture system of mandibular condyles was employed. The distribution of PI3K, phospho-Akt (p-Akt), and PTHrP in condylar cartilage was detected by either immunohistochemistry or immunofluorescence. The second passage chondrocytes and condyle specimens in the organ culture system were treated with PTHrP, LY294002, PTHrP and LY294002 in combination, or dimethyl sulfoxide (DMSO), separately. The mRNA and protein levels of type II (Col II) and type X collagen (Col X) were investigated by real-time polymerase chain reaction (PCR) and Western blot analysis. The condyle growth in organ culture system was analysed by haematoxylin-eosin staining. RESULTS: PTHrP, PI3K, and p-Akt were mainly located in the proliferative and hypertrophic zones. PTHrP promoted the proliferation of condylar chondrocytes, while LY294002 limited this effect. The mRNA and protein levels of Col II and Col X in these cells were reduced by PTHrP and enhanced by LY294002. Organ culture showed a significant enhancement of condyle elongation with PTHrP treatment or a combination of PTHrP and LY294002 treatment. After treatment with LY294002, the length of condyles was reduced compared with the samples treated with DMSO. CONCLUSIONS: We conclude that the PI3K/Akt pathway plays an essential role in the proliferation and differentiation of condylar chondrocytes and is a potential target for PTHrP in regulating chondrocyte differentiation at condylar cartilage.
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Condrócitos/enzimologia , Côndilo Mandibular/citologia , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Western Blotting , Cartilagem/efeitos dos fármacos , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/citologia , Cromonas/farmacologia , Dimetil Sulfóxido/farmacologia , Morfolinas/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND AND METHODS: Commercial pure titanium with nanotopography was prepared via a high-energy shot-peening (HESP) technique. The surface characteristics were evaluated, and the preliminary cell responses to the nanotopographical surface were investigated. RESULTS: The nanotopographical surface layer on titanium was successfully processed by HESP. The average nanoscale grains were approximately 60 nm in diameter and they were nonhomogeneously distributed on the surface. MG-63 cells with an osteogenic phenotype were well adhered and well spread on the nanostructured surface. Compared to the original polished control, the nanotopographical surface highly improved the adhesion, viability, and differentiation of MG-63 cells. CONCLUSION: Titanium with nanotopography achieved by HESP has good cytocompatibility and shows promise for dental implant applications.
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Nanoestruturas/química , Osteoblastos/efeitos dos fármacos , Titânio/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Linhagem Celular Tumoral , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Humanos , Nanoestruturas/toxicidade , Nanotecnologia , Propriedades de Superfície , Titânio/toxicidadeRESUMO
In the present paper, cationic nanoparticles of curcumin, chitosan and poly(É-caprolactone) were developed by a simple nano-precipitation method. The developed curcumin loaded chitosan/poly(É-caprolactone) (chitosan/PCL) nanoparticle showed almost spherical shape and its diameter was varied between 220 nm and 360 nm and zeta potential was varied between +30 mV and 0 mV as a function with pH value. The encapsulation of curcumin into nanoparticles was confirmed by fluorescence spectral analysis. In vitro release study showed the sustained release behavior of curcumin from nanoparticles during the period of 5 days study. In vitro cytotoxicity test revealed the drug concentration dependent on the cell viability against Hela cells and OCM-1 cells after 48 h co-incubation. Furthermore, in vitro cell uptake study revealed that the cell uptake of curcumin was greatly enhanced by encapsulated curcumin into cationic chitosan/PCL nanoparticles. Therefore, the developed cationic chitosan/PCL nanoparticles might be a promising candidate for curcumin delivery to cancer cells.
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Antineoplásicos/administração & dosagem , Quitosana/química , Curcumina/administração & dosagem , Preparações de Ação Retardada/química , Nanopartículas/química , Poliésteres/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacocinética , Curcumina/farmacologia , Células HeLa , Humanos , Nanopartículas/ultraestrutura , Neoplasias/tratamento farmacológicoRESUMO
In this paper, the carboxymethyl chitosan/oxidized dextran hydrogel was developed and its potency application in the prevention of postoperative adhesion was investigated. The developed hydrogel showed porous and interconnected interior structure with pore size about 250 µm, which was sensitive to lysozymic solution (1.5 µg/ml) with almost complete degradation after 4 weeks of in vitro incubation. In vivo study suggested that the developed hydrogel showed the great capacity on the prevention of postoperative adhesions in rat model. According to the result of histopathological examination, it clearly showed that the mesothelial cell layer of abdominal wall and cecum were completely recovered after 7 days of surgery in 3% carboxymethyl chitosan/oxidized dextran hydrogel group, while obvious adhesion between abdominal wall and cecum was observed as treatment with saline solution or 3% carboxymethyl chitosan solution after 1 day of surgery. All these results suggested that the developed biodegradable hydrogel might have potential application in the prevention of postoperative adhesion.
Assuntos
Hidrogel de Polietilenoglicol-Dimetacrilato/administração & dosagem , Polissacarídeos/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Administração Tópica , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacocinética , Quitosana/administração & dosagem , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/química , Quitosana/farmacocinética , Dextranos/administração & dosagem , Dextranos/síntese química , Dextranos/química , Dextranos/farmacocinética , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacocinética , Injeções Intralesionais , Masculino , Modelos Biológicos , Oxirredução , Polissacarídeos/síntese química , Polissacarídeos/química , Polissacarídeos/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
The aim of the study was to investigate a porous nanohydroxyapatite/polyamide 66 (n-HA/PA66) scaffold material that was implanted into muscle and tibiae of 16 New Zealand white rabbits to evaluate the biocompatibility and osteogenesis and osteoinductivity of the materials in vivo. The samples were harvested at 2, 4, 12 and 26 weeks respectively, and subjected to histological analysis. At 2 weeks, the experiment showed that osteogenesis was detected in porous n-HA/PA66 composite and the density of new bone formation was similar to the surrounding host bone at 12 weeks. The study indicated that three-dimensional pore structures could facilitate cell adhesion, differentiation and proliferation, and help with fibrovascular and nerve colonization. In conclusion, porous n-HA/PA66 scaffold material could be a good candidate as a bone substitute material used in clinics due to its excellent histocompatibility, osteoconductivity and osteoinductivity.