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1.
Int J Mol Sci ; 21(1)2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31888070

RESUMO

Metronidazole (MD) is known as a periodontitis medicine and has been widely used in antibiotics for resistance to anaerobic bacteria, periodontal disease, and other threats. To treat diseases, drug delivery carriers are needed with a high bioadhesive property and enhanced drug penetration. Poly (acrylic acid) (PAA) hydrogel films have a good bioadhesive property and are able to localize the absorption site and increase the drug residence time. In this study, we fabricated a MD loaded PAA hydrogel with different MD content (0.1, 0.25, 0.5, and 1 wt%) using varying doses (25, 50, and 75 kGy) and the radiation doses (25, 50, or 75 kGy) in a one-step gamma-ray irradiation process. The chemical and physical structure were determined through a Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy, gel content, and compressive strength. In addition, MD loaded PAA hydrogels were performed to MD release behaviors and cytotoxicity. Finally, we conducted antibacterial activity to demonstrate the prevention of growth of bacteria as a therapeutic dressing. The basic chemical structure analysis of MD was changed greatly at radiation doses of 50 and 75 kGy due to degradation by gamma-ray irradiation. However, when the absorbed dose was 25 kGy, the chemical structure analysis of MD did not change significantly, and the gel content and compressive strength of MD/PAA hydrogel were approximately 80% and 130 kPa, respectively. The MD/PAA hydrogels exhibited no cytotoxicity and good antibacterial activity against Escherichia coli, Staphylococcus aureus, and Streptococcus mutans. These results provide good evidence that MD/PAA hydrogel prepared by gamma-ray irradiation has potential as a competitive candidate for the therapeutic dressing.


Assuntos
Resinas Acrílicas/química , Antibacterianos/farmacologia , Metronidazol/farmacologia , Antibacterianos/química , Sistemas de Liberação de Medicamentos , Escherichia coli/efeitos dos fármacos , Raios gama , Hidrogéis , Metronidazol/química , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos
2.
Int J Mol Sci ; 18(11)2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29068426

RESUMO

Bacterial cellulose (BC) is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR) using an irradiation technique for applications in the dental field. Electron beam irradiation (EI) increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs) were evaluated by scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, thermal gravimetric analysis (TGA), and using wet tensile strength measurements. In addition, in vitro cell studies were conducted in order to confirm the cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k EI-BCMs (100 kGy and 300 kGy irradiated BC membranes) were significantly greater than on NI-BCMs after 3 and 7 days (p < 0.05). Bone regeneration by EI-BCMs and their biodegradabilities were also evaluated using in vivo rat calvarial defect models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited significantly larger new bone area (NBA; %) than 300k EI-BCMs at 8 weeks after implantation (p < 0.05). Mechanical, chemical, and biological analyses showed EI-BCMs effectively interacted with cells and promoted bone regeneration.


Assuntos
Materiais Biocompatíveis/química , Regeneração Óssea , Celulose/efeitos da radiação , Regeneração Tecidual Guiada/métodos , Animais , Bactérias/química , Sobrevivência Celular , Elétrons , Masculino , Teste de Materiais , Camundongos , Microscopia Eletrônica de Varredura , Células NIH 3T3 , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração
3.
Drug Dev Ind Pharm ; 39(12): 1874-80, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22409199

RESUMO

To improve physical properties and modulate the mucoadhesive hydrogel formulation via cross-linking by radiation, hydrogels were prepared using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer carbopol 934P (C934P). As a model drug, naproxen was loaded in the hydrogel formulation. Sol-gel transition temperatures of hydrogels were measured by the tube-inversion method. The mucoadhesive potential of each formulation was determined by measuring the force required to detach the formulation from oral mucosal tissue. To strengthen the mechanical properties, the formulations were irradiated using an electronic beam. Drug release from the hydrogels and the cytotoxicity of each formulation were investigated. Sol-gel transition temperatures of the formulations were decreased by the addition of carbopol and were close to body temperature. The mucoadhesive force of the PF127 formulation was increased by addition of carbopol. In vitro release was sustained and the release rate was reduced by the addition of carbopol. After irradiation, the mucoadhesive force was increased about five-fold especially in the case of PF127 23% (9.7 kPa) and in vitro release was not sustained further. In conclusion, the use of a PF127 formulation incorporating a mucoadhesive polymer could effectively and safely improve oral residence time and absorption of naproxen. Irradiated formulations showed permanent cross-linking and improved properties.


Assuntos
Acrilatos/química , Sistemas de Liberação de Medicamentos , Naproxeno/administração & dosagem , Poloxâmero/química , Adesividade , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/toxicidade , Química Farmacêutica , Composição de Medicamentos , Elétrons , Excipientes/química , Humanos , Hidrogéis , Células KB , Mucosa Bucal/metabolismo , Naproxeno/farmacocinética , Naproxeno/toxicidade , Transição de Fase , Suínos , Temperatura , Testes de Toxicidade
4.
Int J Mol Sci ; 14(6): 11011-23, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23708101

RESUMO

In this study, we developed a one step process to synthesize nanogel containing silver nanoparticles involving electron beam irradiation. Water-soluble silver nitrate powder is dissolved in the distilled water and then poly(acrylic acid) (PAAc) and hexane are put into this silver nitrate solution. These samples are irradiated by an electron beam to make the PAAc nanogels containing silver nanoparticles (Ag/PAAc nanogels). The nanoparticles were characterized by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). In addition, the particle size and zeta-potential were confirmed by a particle size analyzer (PSA). The antibacterial properties of the nanogels were evaluated by paper diffusion test. The Ag/PAAc nanogels had an antibacterial effect against Escherichia coli and Staphylococcus aureus. The nanogels also demonstrated a good healing effect against diabetic ulcer. The size of the Ag/PAAc nanogels decreased with increasing irradiation doses, and the absolute value of the zeta potential increased with increasing irradiation doses. Also, the Ag/PAAc nanogels exhibited good antibacterial activity against both Gram-negative and Gram-positive bacteria. In in vivo wound healing, the Ag/PAAc nanogels have a good healing effect.


Assuntos
Resinas Acrílicas/farmacologia , Anti-Infecciosos/farmacologia , Elétrons , Nanopartículas Metálicas/química , Polietilenoglicóis/farmacologia , Polietilenoimina/farmacologia , Prata/farmacologia , Animais , Escherichia coli/efeitos dos fármacos , Feminino , Camundongos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanogéis , Tamanho da Partícula , Espectrometria por Raios X , Espectrofotometria Ultravioleta , Staphylococcus aureus/efeitos dos fármacos , Eletricidade Estática , Cicatrização/efeitos dos fármacos
5.
J Nanosci Nanotechnol ; 12(1): 743-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22524050

RESUMO

In this study, carboxymethyl cellulose (CMC) hydrogels were traditionally prepared by gamma-ray with an absorbed dose of 50 kGy from a 60Co source. The CMC hydrogels were absorbed and swelled in silver nitrate aqueous solution (0.01 M) by dipping for 1 hour, and then irradiated by gamma-ray at various doses to form silver nanoparticles (Ag NPs). The UV-Vis analysis indicated that the concentration of Ag NPs was enhanced by increasing of absorbed dose from 1 to 5 kGy in this situ reducing system. The FE-SEM and XPS measurements provided further evidence for the successful formation of Ag NPs. These CMC hydrogels stabilized Ag NPs also have been investigated for inhibiting the growth of Staphylococcus aureus and Escherichia coli strains in liquid as well as on solid growth media. The antibacterial tests indicated that the hydrogels containing Ag NPs have antibacterial activity.


Assuntos
Carboximetilcelulose Sódica/química , Cristalização/métodos , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Prata/química , Carboximetilcelulose Sódica/efeitos da radiação , Raios gama , Hidrogéis/química , Hidrogéis/efeitos da radiação , Teste de Materiais , Tamanho da Partícula , Doses de Radiação
6.
Materials (Basel) ; 15(23)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36500136

RESUMO

PCL nanofibrous scaffolds are widely used as bone scaffolds, and they can increase the efficiency of bone regeneration by loading drugs and/or growth factors onto them. However, to obtain a more effective bone regeneration effect, it is necessary to increase drug loading and release efficiency. In this study, conductive hydrogel forming nanofibrous scaffolds were prepared to increase drug efficiency. GO has an excellent conductivity and biocompatibility, making it an efficient conductive polymer for bone differentiation. Electrospun PCL was immersed in a mixed solution of GO and PVP and then crosslinked using gamma-ray irradiation. It was confirmed that GO/PVP-PCL was successfully prepared through its characterization (morphology, thermal, chemical, electrical, and biological properties). In addition, drug-release efficiency was confirmed by electrical stimulation after loading the sample with BMP-2, a bone-regeneration growth factor. Compared to PCL, it was confirmed that GO/PVP-PCL has an approximately 20% improved drug-release efficiency and an excellent mineralization of the scaffolds using SBF. After culturing MG63 cells on GO/PVP-PCL, a high effect on osteodifferentiation was confirmed by ALP activity. Therefore, GO/PVP-PCL prepared by a gamma-ray-induced crosslinking reaction is expected to be used as biomaterial for bone-tissue engineering.

7.
Polymers (Basel) ; 14(6)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35335595

RESUMO

The effectiveness of small-diameter vascular grafts depends on their antithrombogenic properties and ability to undergo accelerated endothelialization. The extreme hydrophobic nature of poly(ε-caprolactone) (PCL) hinders vascular tissue integration, limiting its use in medical implants. To enhance the antithrombogenicity of PCL as a biomaterial, we grafted 2-aminoethyl methacrylate (AEMA) hydrochloride onto the PCL surface using gamma irradiation; developed a biodegradable heparin-immobilized PCL nanofibrous scaffold using gamma irradiation and N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride/N-hydroxysuccinimide reaction chemistry; and incorporated vascular endothelial growth factor (VEGF) into the scaffold to promote vascular endothelial cell proliferation and prevent thrombosis on the vascular grafts. We assessed the physicochemical properties of PCL, heparin-AEMA-PCL (H-PCL), and VEGF-loaded heparin-AEMA-PCL (VH-PCL) vascular grafts using scanning electron microscopy, attenuated total reflection-Fourier transform infrared spectroscopy, toluidine blue O staining, and fibrinogen adsorption and surface wettability measurement. In addition, we implanted the vascular grafts into 24-month-old Sprague Dawley rats and evaluated them for 3 months. The H-PCL and VH-PCL vascular grafts improved the recovery of blood vessel function by promoting the proliferation of endothelial cells and preventing thrombosis in clinical and histological evaluation, indicating their potential to serve as functional vascular grafts in vascular tissue engineering.

8.
Biomater Sci ; 11(1): 298-306, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36448579

RESUMO

In an immunosuppressive tumor microenvironment, tumor-associated macrophages (TAMs) are the most abundant cells displaying pro-tumorigenic M2-like phenotypes, encouraging tumor growth and influencing the development of resistance against conventional therapies. TAMs are highly malleable. They can be repolarized into tumoricidal M1-like cells. In this study, we report the synthesis of novel co-operative immuno-photodynamic nanoparticles involving TAM self-targeting acrylic acid grafted mannan (a polysaccharide) conjugated with the chlorin e6 (Ce6) photosensitizer and then loaded with resiquimod (R848), a toll-like receptor (TLR7/8) agonist. The mannan conjugated Ce6 loaded with R848 (MCR) as bioconjugate nanoparticles demonstrated selective targeting of anti-inflammatory M2-like cells. Using photodynamic therapy they were repolarized to pro-inflammatory M1-like cells with combined effects of reactive oxygen species (ROS)-triggered intracellular signaling and a small-molecule immunostimulant. The MCR also demonstrated a TAM-directed adaptive immune response, inhibited tumor growth, and prevented metastasis. Our results indicate that these MCR nanoparticles can effectively target TAMs and modulate them for cancer immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Mananas , Macrófagos Associados a Tumor , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
9.
J Nanosci Nanotechnol ; 11(8): 7483-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22103225

RESUMO

High density polyethylene (HDPE) membrane filled with alumina particles was prepared by a wet process for a Li-ion secondary battery. Soybean oil and dibutyl phthalate (DBP) were premixed as the co-diluents. Gamma ray irradiation was used for crosslinking of HDPE. The HDPE membrane filled with alumina particles had excellent mechanical property and thermal stability due to the alumina particles and irradiation crosslinking. The tensile strength of the membrane increased with an increased amount of alumina up to 15 wt%. The thermal shrinkage of the membrane decreased with an increased amount of alumina up to 15 wt%. The electrochemical stability of the irradiated membrane after extraction was improved with irradiation dose up to 50 kGy.

10.
Carbohydr Polym ; 258: 117718, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593580

RESUMO

Herein, carboxymethyl chitosan and poly(vinylpyrrolidone) based hydrogels were synthesized by electron beam irradiation with dose variations (15 kGy, 30 kGy, and 45 kGy) for drug delivery applications. Irradiation crosslinked hydrogels were characterized for swellings in different medias, chemical, thermal, cell cytotoxicity, and drug release aspects. Swelling analysis was evaluated in distilled water, buffer, and saline solutions. Fourier transform infrared analysis revealed the establishment of physical interactions and confirmed the presence of functional groups present in the drug carriers. Scanning electron microscopy depicted the porous structure, which is responsible for swelling, drug loading, and release. Cell cytotoxicity assays indicated good cell viability on RAW 264.7 cells and anticancer activity on cancerous AGS cell lines. Cumulative drug release (%) of kanamycin in PBS at pH 7.4 was more than 90 % at 168 h. These drug carriers show promise to be developed as a sustained drug delivery system.


Assuntos
Antineoplásicos/administração & dosagem , Quitosana/análogos & derivados , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Canamicina/administração & dosagem , Povidona/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Quitosana/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Difusão , Liberação Controlada de Fármacos , Elétrons , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Canamicina/farmacologia , Camundongos , Microscopia Eletrônica de Varredura , Porosidade , Células RAW 264.7 , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Adv Healthc Mater ; 10(18): e2100636, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34235891

RESUMO

Plasmonic photothermal therapy (PPTT) using gold nanoparticles (AuNPs) has shown great potential for use in selective tumor treatment, because the AuNPs can generate destructive heat preferentially upon irradiation. However, PPTT using AuNPs has not been added to practice, owing to insufficient heating methods and tissue temperature measurement techniques, leading to unreliable and inaccurate treatments. Because the photothermal properties of AuNPs vary with laser power, particle optical density, and tissue depth, the accurate prediction of heat generation is indispensable for clinical treatment. In this report, bioprinted 3D complex tissue constructs comprising processed gel obtained from porcine skin and human decellularized adipose tissue are presented for characterization of the photothermal properties of gold nanorods (AuNRs) having an aspect ratio of 3.7 irradiated by a near-infrared laser. Moreover, an analytical function is suggested for achieving PPTT that can cause thermal damage selectively on early-stage human breast cancer by regulating the heat generation of the AuNRs in the tissue.


Assuntos
Neoplasias da Mama , Nanopartículas Metálicas , Nanotubos , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Feminino , Ouro , Humanos , Nanopartículas Metálicas/uso terapêutico , Fototerapia
12.
J Mater Chem B ; 8(32): 7225-7232, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32638708

RESUMO

Bioelectrodes, including metallic and conductive polymer (CP) bioelectrodes, often suffer from biofouling by contamination from microbacteria and/or biomolecules in biological systems, which can cause substantial impairment of biofunctionality and biocompatibility. Herein, we have employed an in situ polymerization of methacryloyloxyethyl phosphorylcholine (MPC) by gamma radiation to introduce fouling-resistant properties onto the surface of the conductive polymer, polypyrrole (PPy). The concentrations of an MPC monomer were varied during the grafting. PPy electrodes modified with MPC (PPy-g-MPC) revealed excellent anti-biofouling properties, as demonstrated by multiple analyses, such as serum protein adsorption, fibroblast adhesion, bacteria adhesion, and scar tissue formation in vivo. Importantly, PPy-g-MPC, which was modified with 0.2 M MPC using gamma radiation, exhibited electrical properties similar to unmodified PPy electrodes, indicating that our MPC grafting strategies did not cause impairment of electrical/electrochemical properties of the original PPy electrodes while successfully introducing anti-biofouling properties. Zwitterionic MPC polymer grafting on PPy electrodes by in situ polymerization with gamma radiation will benefit the development of highly biocompatible and functional bioelectrodes, such as neural electrodes, stimulators, and biosensors.


Assuntos
Incrustação Biológica/prevenção & controle , Materiais Biomiméticos/química , Metacrilatos/química , Fosforilcolina/química , Polímeros/química , Pirróis/química , Células 3T3 , Adsorção , Animais , Antibacterianos , Aderência Bacteriana , Proteínas Sanguíneas/química , Cicatriz/metabolismo , Condutividade Elétrica , Técnicas Eletroquímicas , Eletrodos , Escherichia coli , Fibroblastos/química , Raios gama , Camundongos , Camundongos Endogâmicos BALB C , Polimerização , Staphylococcus aureus , Propriedades de Superfície
13.
Polymers (Basel) ; 12(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948023

RESUMO

Conducting polymer (CP)-based hydrogels exhibit the behaviors of bending or contraction/relaxation due to electrical stimulation. They are similar in some ways to biological organs and have advantages regarding manipulation and miniaturization. Thus, these hydrogels have attracted considerable interest for biomedical applications. In this study, we prepared PPy/PVP hydrogel with different concentrations and content through polymerization and cross-linking induced by gamma-ray irradiation at 25 kGy to optimize the mechanical properties of the resulting PPy/PVP hydrogel. Optimization of the PPy/PVP hydrogel was confirmed by characterization using scanning electron microscopy, gel fraction, swelling ratio, and Fourier transform infrared spectroscopy. In addition, we assessed live-cell viability using live/dead assay and CCK-8 assay, and found good cell viability regardless of the concentration and content of Py/pTS. The conductivity of PPy/PVP hydrogel was at least 13 mS/cm. The mechanical properties of PPy/PVP hydrogel are important factors in their application for biomaterials. It was found that 0.15PPy/PVP20 (51.96 ± 6.12 kPa) exhibited better compressive strength than the other samples for use in CP-based hydrogels. Therefore, it was concluded that gamma rays can be used to optimize PPy/PVP hydrogel and that biomedical applications of CP-based hydrogels will be possible.

14.
Carbohydr Polym ; 241: 116284, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32507170

RESUMO

Gradual wear and tear can cause a local inflammatory response in tendons. The trauma and inflammatory reaction eventually impair the biomechanical properties of the tendon. In this study, we prepared lactoferrin-immobilized, heparin-anchored, poly(lactic-co-glycolic acid) nanoparticles (LF/Hep-PLGA NPs) and evaluated their in vitro anti-inflammatory effects on interleukin-1ß (IL-1ß)-treated tenocytes and in vivo tendon healing effects in a rat model of Achilles tendinitis. Long-term LF-deliverable NPs (LF/Hep-PLGA NPs) remarkably decreased mRNA levels of pro-inflammatory factors [cyclooxygenase-2 (COX-2), IL-1ß, matrix metalloproteinase-3 (MMP-3), MMP-13, IL-6, and tumor necrosis factor-α (TNF-α)] and increased mRNA levels of anti-inflammatory cytokines (IL-4 and IL-10) in both IL-1ß-treated tenocytes and the Achilles tendons of a collagenase-induced Achilles tendinitis rat model. Interestingly, anti-inflammatory LF/Hep-PLGA NPs greatly enhanced collagen content, mRNA levels of tenogenic markers [collagen type I (COL1A1), decorin (DCN), tenascin-C (TNC)], and biomechanical properties such as tendon stiffness and tensile strength. These results suggest that anti-inflammatory LF/Hep-PLGA NPs are effective at restoring tendons in Achilles tendinitis.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Anti-Inflamatórios/administração & dosagem , Heparina/administração & dosagem , Lactoferrina/administração & dosagem , Nanopartículas/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Tendinopatia/tratamento farmacológico , Tendão do Calcâneo/metabolismo , Tendão do Calcâneo/patologia , Tendão do Calcâneo/fisiologia , Animais , Anti-Inflamatórios/química , Colágeno/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Heparina/química , Lactoferrina/química , Masculino , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Tendinopatia/genética , Tendinopatia/metabolismo , Tendinopatia/patologia , Tenócitos/efeitos dos fármacos , Resistência à Tração
15.
Biomed Res Int ; 2020: 5052028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090096

RESUMO

Achilles tendinitis caused by overuse, aging, or gradual wear induces pain, swelling, and stiffness of Achilles tendon and leads to tendon rupture. This study was performed to investigate the suppression of inflammation responses in interleukin-1ß- (IL-1ß-) stimulated tenocytes in vitro and the suppression of the progression of Achilles tendinitis-induced rat models in vivo using dexamethasone-containing porous microspheres (DEX/PMSs) for a sustained intratendinous DEX delivery. DEX from DEX/PMSs showed the sustained release of DEX. Treatment of IL-1ß-stimulated tenocytes with DEX/PMSs suppressed the mRNA levels for COX-2, IL-1ß, IL-6, and TNF-α. The intratendinous injection of DEX/PMSs into Achilles tendinitis rats both decreased the mRNA levels for these cytokines and increased mRNA levels for anti-inflammatory cytokines IL-4 and IL-10 in tendon tissues. Furthermore, DEX/PMSs effectively prevented tendon degeneration by enhancing the collagen content and biomechanical properties. Our findings suggest that DEX/PMSs show great potential as a sustained intratendinous delivery system for ameliorating inflammation responses as well as tendon degeneration in Achilles tendinitis.


Assuntos
Tendão do Calcâneo/patologia , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Inflamação/tratamento farmacológico , Microesferas , Tendinopatia/tratamento farmacológico , Tendão do Calcâneo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Morte Celular/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Hidroxiprolina/metabolismo , Inflamação/complicações , Mediadores da Inflamação/metabolismo , Masculino , Porosidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Suínos , Tendinopatia/complicações , Resistência à Tração , Resultado do Tratamento
16.
Biomacromolecules ; 9(7): 1772-81, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18558737

RESUMO

Controlled adhesion and continuous growth of human mesenchymal stem cells (hMSCs) are essential for scaffold-based delivery of hMSCs in tissue engineering applications. The main goal of this study is to develop biofunctionalized synthetic substrates to actively control adhesion, spreading, and proliferation of hMSCs. gamma-Ray irradiation was employed to graft acrylic acid (AAc) to biodegeradable poly(L-lactide-co--caprolactone) (PLCL) films. Gelatin, a natural polymer, was then immobilized on the AAc grafted PLCL film (AAc-PLCL) to induce biomimetic interactions with the cells. The graft yield of AAc increased as the irradiation dose and AAc concentration increased, and the presence of gelatin (gelatin-AAc-PLCL) following immobilization was confirmed using ESCA. To investigate cell responses, hMSCs isolated from a human mandible were cultured on the various substrates and their adhesion, spreading, and proliferation were examined. After three days of culture, the DNA concentration from the cells cultured on gelatin-AAc-PLCL film was 2.9-fold greater than that on the PLCL film. Immunofluorescent staining of hMSCs cultured on the gelatin-AAc-PLCL films demonstrated homogeneous localization of F-Actin and vinculin in their cytoplasm, while mature adhesive structure was not observed from the cells cultured on other substrates. Furthermore, the ratio of projected area of adherent single cells on gelatin-AAc-PLCL films was significantly larger (116.80 +/- 12.78%) than that on the PLCL films (30.11 +/- 5.07%). Our results suggest that gelatin-immobilized PLCL substrates may be potentially used in tissue engineering, particularly as a stem cell delivery carrier for the regeneration of target tissue.


Assuntos
Células-Tronco Mesenquimais/citologia , Polímeros/síntese química , Engenharia Tecidual/métodos , Acrilatos , Adesão Celular , Diferenciação Celular , Proliferação de Células , Forma Celular , Gelatina , Humanos , Poliésteres , Polímeros/química
17.
Sci Rep ; 8(1): 3721, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29487343

RESUMO

Conductive polymers, including polypyrrole (PPy), have been extensively explored to fabricate electrically conductive biomaterials for bioelectrodes and tissue engineering scaffolds. For their in vivo uses, a sterilization method without severe impairment of original material properties and performance is necessary. Gamma-ray radiation has been commonly applied for sterilization of medical products because of its simple and uniform sterilization without heat generation. Herein we describe the first study on gamma-ray sterilization of PPy bioelectrodes and its effects on their characteristics. We irradiated PPy bioelectrodes with different doses (0-75 kGy) of gamma-rays. Gamma-ray irradiation of the PPy (γ-PPy) increased the oxygenation and hydrophilicity of the surfaces. Interestingly, gamma-ray irradiation did not alter the electrical impedances and conductivities of the PPy substrates. Additionally, γ-PPy prepared with various dopants (e.g., para-toluene sulfonate, polystyrene sulfonate, and chlorine) showed the electrochemical properties similar to the non-irradiated control. Gamma-ray irradiation at doses of ≥15 kGy was required for effective sterilization as evidenced by complete eradication of gram positive and negative bacteria. γ-PPy substrates also showed cytocompatibility similar to untreated control PPy, indicating no substantial alteration of cytocompatibility. In conclusion, gamma ray sterilization is a viable method of sterilization of conducting polymer-based biomaterials for biomedical applications.

18.
Materials (Basel) ; 11(12)2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30545019

RESUMO

This study aimed to evaluate the titanium (Ti) implants coated with collagen type Ⅰ crosslinked using gamma-irrigation or glutaraldehyde (GA). The in vitro surface observations, quantification assay, and cell studies using human mesenchymal stem cells (hMSCs) were conducted. For in vivo experiments, the implants were divided into three groups and inserted into the rat tibias: control group (non-treated Ti implant), GA group (Ti implants coated with GA-crosslinked collagen) and 25 kGy group (Ti implants coated with gamma-radiation-crosslinked collagen at dose of 25 kGy). The animals were sacrificed at 4 weeks after implantation and the tissue sections were obtained. New bone volume (mm³) and bone-to-implant contact (BIC, %) within the region of interest (ROI) was measured. The in vitro results showed the highest osteogenic differentiation and levels of osteogenesis-related gene expressions in the 25 kGy group without cytotoxicity. The new bone volume of GA group was significantly higher than the control (p < 0.05). In the result of the BIC, the 25 kGy group was significantly higher than the control (p < 0.05). However, there was no significant difference between the experimental groups. Within the limitations of this study, Ti implant coated with gamma-radiation-crosslinked collagen has potential utility without side effects from chemical agents.

19.
Int J Nanomedicine ; 13: 525-536, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29416333

RESUMO

INTRODUCTION: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. MATERIALS AND METHODS: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. RESULTS: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. CONCLUSION: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers.


Assuntos
Raios gama , Terapia Genética , Neoplasias/genética , Neoplasias/terapia , Animais , Quitosana/química , DNA/metabolismo , Sistemas de Liberação de Medicamentos , Células HCT116 , Hemólise , Humanos , Metacrilatos/química , Camundongos , Plasmídeos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Solubilidade , Transfecção , Água/química
20.
Int J Biol Macromol ; 118(Pt A): 333-339, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29909030

RESUMO

ß-Glucan can provide excellent environment to apply to drug carrier due to its immunological and anti-inflammatory effect. Minocycline hydrochloride (MH) has excellent oral bioavailability pharmacological properties. Specifically, MH is effectively absorbed into the gingiva for periodontal disease treatment. In this study, we attempt to develop MH loaded ß-glucan hydrogel for periodontal disease treatment through radiation-crosslinking technique. In addition, MH loaded ß-glucan hydrogels were tested for their cytotoxicity and antibacterial activity. Finally, we conducted an in vivo study to demonstrate the potential to prevent the invasion of bacteria to treat periodontal disease. The gel content and compressive strength of the ß-glucan hydrogels increased as the ß-glucan content and the absorbed dose (up to 7 kGy) increased. For a radiation dose of 7 kGy, the gelation and the compressive strength of a 6 wt% ß-glucan hydrogel were approximately 92% and 270 kPa, respectively. As a drug, MH was consistently released from ß-glucan hydrogels, reaching 80% at approximately 90 min. Furthermore, the MH loaded ß-glucan hydrogels showed no cytotoxicity. The MH loaded ß-glucan hydrogels exhibited good antibacterial activity against Porphyromonas gingivalis. In addition, MH loaded ß-glucan hydrogel demonstrated the potential of a good capability to prevent the invasion of bacteria and to treat wounds.


Assuntos
Antibacterianos/química , Portadores de Fármacos/química , Hidrogéis/química , beta-Glucanas/química , Antibacterianos/uso terapêutico , Quitosana/química , Portadores de Fármacos/uso terapêutico , Humanos , Reologia
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