RESUMO
For the precise treatment of tumors, it is necessary to develop a theranostic nanoplatform that has both diagnostic and therapeutic functions. In this article, we designed a new theranostic probe for fluorescence imaging of Zn2+ and fluorescence/MRI guided magnetically targeted photodynamic-photothermal therapy. The fluorescence imaging of Zn2+ was based on an endogenous ATP-driven DNA nanomachine that could perform repetitive stand displacement reaction. It modifies all units on a single PDA/Fe3O4 nanoparticle containing a hairpin-locked initiated strand activated by a target molecule in cells, a two-stranded fuel DNA triggered by ATP, and a two-stranded DNA track responding to an initiated strand and fuel DNA. After entering the cell, the intracellular target Zn2+ initiates the nanomachine via an autocatalytic cleavage reaction, and the machine programmatically and gradually runs on the assembled DNA track via fuel DNA driving and the intramolecular toehold-mediated stand displacement reaction. The Fe3O4 core first exhibits magnetic targeting, increasing the ability of nanoparticles to enter tumor cells at the tumor site. The Fe3O4 could also be employed as a powerful magnetic resonance imaging (MRI) contrast agent and guided therapy. Using 808 nm laser and 635 nm laser irradiation together at the tumor site, the PDA nanoshell produced an excellent photothermal effect and the TMPyP4 molecules entering the cell generated reactive oxygen species, followed by cell damage. A series of reliable experiments suggested that the Fe3O4@PDA@DNA nanoprobe showed superior fluorescence specificity, MRI, a remarkable photothermal/photodynamic therapy effect, and favorable biocompatibility. This theranostic nanoplatform offered a split-new insight into tumor fluorescence and MRI diagnosis as well as effective tumor therapy.
Assuntos
DNA/química , Óxido Ferroso-Férrico/química , Indóis/química , Imageamento por Ressonância Magnética , Imagem Óptica , Fotoquimioterapia/métodos , Polímeros/química , Zinco/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Estudos de Viabilidade , Humanos , Espaço Intracelular/metabolismo , Células MCF-7 , Camundongos , Nanomedicina TeranósticaRESUMO
A pH-sensitive and double functional nanoprobe was designed and synthesized in a water-soluble system using thioglycolic acid (TGA) and mercapto-acetohydrazide (TGH) as the stabilizers. TGA is biocompatible because the carboxyl group is easily linked to biological macromolecules. At the same time, the hydrazide on TGH reacts with the aldehyde on poly(ethylene glycol) (PEG) and forms a hydrazone bond. The hydrazone bond ruptured at specific pH values and exhibited pH-stimuli-responsive characteristics. As an optical imaging probe, the PEG-TGA/TGH-capped CdTe quantum dots (QDs) had high quality, with a fluorescence efficiency of 25-30%, and remained stable for at least five months. This pH-responsive factor can be used for the effective release of CdTe QDs under the acidic interstitial extracellular environment of tumor cells. This allows the prepared pH-stimuli-responsive nanoprobes to show fluorescence signals for use in cancer cell imaging.
Assuntos
Compostos de Cádmio/química , Microscopia de Fluorescência/métodos , Polietilenoglicóis/química , Pontos Quânticos/química , Telúrio/química , Tioglicolatos/química , Corantes Fluorescentes/química , Células HeLa , Células Hep G2 , Humanos , Hidrazonas/química , Concentração de Íons de Hidrogênio , Sondas Moleculares/química , Nanocompostos/química , Tamanho da Partícula , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
We present a triple-mode nanosensor platform for nucleic acid detection utilizing fluorescence anisotropy and Förster resonance energy transfer (FRET) strategies. The self-assembled nanoprobes serve as mass amplifiers, nanoquenchers, or nanodonors, exhibiting high FRET efficiencies (64.4-86.5%) and demonstrating excellent detection capabilities in DNA and microRNA analysis.
Assuntos
DNA , Transferência Ressonante de Energia de Fluorescência , MicroRNAs , Polímeros , DNA/química , Polímeros/química , MicroRNAs/análise , Corantes Fluorescentes/química , Polarização de Fluorescência , Fluorescência , Técnicas Biossensoriais/métodosRESUMO
Bacterial invasion hinders the healing process of wound, leading to the formation of chronic infected wound; meanwhile, the misuse of antibiotics has resulted in the emergence of numerous drug-resistant bacteria. The application of conventional antimicrobial methods and wound treatment techniques is not appropriate for wound dressings. In this paper, quaternized poly(vinyl alcohol) (QPVA) and pomegranate-like copper uniformly doped polydopamine nanoparticles (PDA@Cu) were introduced into a gelatin-oxidized carboxymethyl cellulose system to form a multicomponent synergistic antibacterial hydrogel (GOQ3P3). Polydopamine improves the biocompatibility and prevents the detachment of Cu nanoparticles. It can achieve synergistic antibacterial effects through quaternary ammonium salt-inorganic nanoparticle photothermal treatment under 808 nm near-infrared (NIR) irradiation. It exhibits highly efficient and rapid bactericidal properties against Escherichia coli, Staphylococcus aureus, and MRSA (methicillin-resistant Staphylococcus aureus) with an antibacterial rate close to 100%. The gel scaffold composed of macromolecules gives the hydrogel excellent mechanical properties, adhesive capabilities, self-healing characteristics, biocompatibility, and pH degradation and promotes cell adhesion and migration. In a full-thickness wound healing model infected with MRSA, GOQ3P3 controls inflammatory responses, accelerates collagen deposition, promotes angiogenesis, and enhances wound closure in the wound healing cascade reaction. This study provides a feasible strategy for constructing dressings targeting chronic infection wounds caused by drug-resistant bacteria.
Assuntos
Antibacterianos , Materiais Biocompatíveis , Carboximetilcelulose Sódica , Escherichia coli , Gelatina , Hidrogéis , Teste de Materiais , Testes de Sensibilidade Microbiana , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Gelatina/química , Cicatrização/efeitos dos fármacos , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Escherichia coli/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Tamanho da Partícula , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Cobre/química , Cobre/farmacologia , HumanosRESUMO
Tumor-associated macrophages (TAMs) play a critical role in tumor progression and metastasis. Modulation of TAM polarization is one of the most effective strategies to change the immunosuppressive tumor microenvironment (TME). In this study, organic polymer nanoparticles (CPHT) were prepared using hyaluronic acid (HA)-conjugated disulfide-bonded polyethylene imide (PEIS) as a carrier through a self-assembly strategy. These nanoparticles were modified by transferrin (Tf) and loaded with chlorin e6 (Ce6). The results showed that CPHT had good dispersion with a particle size of about 30 nm. CPHT gradually disintegrated under the exposure with a high concentration of glutathione (GSH) in tumor cells, proving the possibility for the controlled release of Ce6 and photodynamic therapy. An in vitro test showed that the uptake of CPHT in tumor cells was mediated by both HA and Tf, indicating the active tumor-targeting capacity of CPHT. CPHT significantly downregulated the ratio of CD206/CD86 and triggered the upregulation of immune factors such as TNF-α and iNOS, suggesting the repolarization of TAMs. We also found that CPHT effectively induced ferroptosis in tumor cells through lipid peroxide accumulation, GSH depletion, and downregulation of lipid peroxidase (GPX4) expression. Animal experiments confirmed that CPHT not only effectively inhibited the growth of tumors in situ but also significantly decelerated the growth of the distal tumor. Elevated levels of CD86 and IFN-γ and decreased expression of CD206 were observed at the tumor sites post CPHT treatment. These results confirmed the value of CPHT as a multifunctional nanoplatform that can tune the TME and provide new hope for tumor treatment.
Assuntos
Neoplasias da Mama , Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Humanos , Feminino , Polímeros/farmacologia , Macrófagos Associados a Tumor , Porfirinas/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral , Fármacos Fotossensibilizantes/farmacologiaRESUMO
Flexible electronic devices with biological therapeutic and sensing properties are one of the current research directions. Here, a multifunctional hydrogel for stress sensing and wound healing was prepared by a simple one-pot method and a solution replacement method. Among them, zwitterionic polymers promote wound healing by promoting the polarization of M2 macrophages, collagen deposition, and blood vessel formation. Glycerin can significantly improve the resilience and frost resistance of the hydrogel, ensuring that a sensor made using the hydrogel can work normally in a cold environment. In addition, zwitterionic polymers are highly biocompatible, providing excellent antibacterial adhesion to aid the wound healing process, and good electrical conductivity enhances sensing sensitivity and stability. Based on these properties, multifunctional hydrogels could detect human vital activities while promoting wound healing, providing new ideas for the fields of diagnosis and wound dressing.
Assuntos
Incrustação Biológica , Hidrogéis , Incrustação Biológica/prevenção & controle , Condutividade Elétrica , Humanos , Hidrogéis/farmacologia , Polímeros , CicatrizaçãoRESUMO
Low eutectic of lauric acid and stearic acid is one of drug loading candidates for its phase transformation at a certain temperature. Herein we demonstrated a combined photothermal-chemotherapy for breast cancer with near-infrared (NIR) triggered phase transition materials (PCM), which was conjugated with polydopamine (PDA) as the photosensitive agent. The PCM nanoparticles had diameters of ~75 nm based on scanning electron microscope (SEM) and dynamic laser scattering (DLS) measurement. Systematic in vitro and in vivo studies have been performed to investigate the stability, biosafety, photothermal performance, and drug delivery and release of PCM conjugates. Temperature measurement confirmed the prepared PDA modified material still showed strong photothermal effect after five cycles, which was higher than that of IR780 conjugated ones. In vivo photothermal imaging showed that the temperature of the tumor site reached 50.8 °C after 3 h of intravenous injection of PCM conjugates. More effective therapy of near-infrared (NIR)-assisted PDA-M@PCM in 4T1 bearing mice was witnessed when compared with that of non-NIR-assisted ones. Enhanced therapy in 4T1 tumor was demonstrated in DOX-loaded PDA-M@PCM by fluorescence imaging. This NIR-triggered PCM based nanoplatform can serve as useful tool for light-assisted combined tumor therapy.
Assuntos
Neoplasias da Mama/terapia , Ácidos Graxos/química , Indóis/química , Raios Infravermelhos , Polímeros/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Camundongos , Transição de Fase , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O2 and H2O2 self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co2+ and release CaO2 and graphene quantum dots (GQDs). The exposed CaO2 reacted with water to generate H2O2 and O2. The self-supplied O2 alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H2O2 was catalyzed by endogenous Co2+ to produce hydroxyl radicals for Co2+-triggered CDT. In vitro and in vivo experiments confirm that CaO2/GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO2/GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO2/GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway.
Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Peróxido de Hidrogênio/farmacologia , Imidazóis/farmacologia , Oxigênio/farmacologia , Fotoquimioterapia , Infecção dos Ferimentos/tratamento farmacológico , Zeolitas/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/química , Escherichia coli/efeitos dos fármacos , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Imidazóis/química , Teste de Materiais , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nanopartículas/química , Oxigênio/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Infecção dos Ferimentos/metabolismo , Zeolitas/químicaRESUMO
Natural polymer materials have attracted great attention in the field of hemostasis because of their wide range of source, nontoxicity, hydrophilicity, and air permeability. In the present study, two natural polymers composed of carboxymethyl chitosan (CMCS) and sodium carboxymethylcellulose (CMCNa) plus γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH560) that serves as a crosslinking agent were selected to synthesize a capillary-mimicking composite hemostatic (CCK) sponge with a low density, interconnected microchannel architecture, suitable mechanical strength, high resilience, and ultrastrong liquid absorption capacity. The introduction of a large number of hydrophilic carboxymethyl functional groups and the design of capillary-mimicking structures formed by the ice segregation-induced self-assembly (ISISA) process endowed the CCK sponges with an ultrastrong liquid absorption capacity, which significantly enhanced the hemostatic ability of the materials. Both in vivo and in vitro hemostatic experiments confirmed the potential of the CCK sponges to achieve rapid hemostasis. Additionally, cytotoxicity and hemolysis assays showed that the CCK sponges exhibited good biocompatibility and hemocompatibility. The possible hemostatic mechanism was also discussed in this study. In conclusion, the capillary-mimicking hemostatic sponge exhibits a high potential to induce rapid hemostasis in prehospital emergency and clinical settings. STATEMENT OF SIGNIFICANCE: In the present study, an oriented composite hemostatic (CCK) sponge with a capillary-mimicking structure formed by the ice segregation-induced self-assembly (ISISA) process was designed and used to achieve rapid hemostasis. The unique aligned microchannel structure of the sponge exhibited an ultrastrong capillary-mimicking action and endowed the prepared CCK hemostatic sponge with a strong liquid absorption capacity. By changing the proportion of raw materials, we could modify the unique capillary-mimicking structure with aligned microchannels. Two natural polymer-based materials with abundant hydrophilic groups were chosen to prepare the CCK sponge to fully utilize the characteristics of this structure. The oriented natural polymer-based porous sponge with capillary-mimicking microchannels exhibited a strong hemostatic ability in both in vivo and in vitro tests. The results showed that the CCK sponge with the capillary-mimicking structure has a high potential to achieve rapid hemostasis.
Assuntos
Hemostáticos , Polímeros , Bandagens , Hemostasia , Hemostáticos/farmacologia , Polímeros/farmacologia , PorosidadeRESUMO
Biocompatible carboxyethyl chitosan/poly(vinyl alcohol) (CECS/PVA) nanofibers were successfully prepared by electrospinning of aqueous CECS/PVA solution. The composite nanofibrous membranes were subjected to detailed analysis by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). SEM images showed that the morphology and diameter of the nanofibers were mainly affected by the weight ratio of CECS/PVA. XRD and DSC demonstrated that there was strong intermolecular hydrogen bonding between the molecules of CECS and PVA. The crystalline microstructure of the electrospun fibers was not well developed. The potential use of the CECS/PVA electrospun fiber mats as scaffolding materials for skin regeneration was evaluated in vitro using mouse fibroblasts (L929) as reference cell lines. Indirect cytotoxicity assessment of the fiber mats indicated that the CECS/PVA electrospun mat was nontoxic to the L929 cell. Cell culture results showed that fibrous mats were good in promoting the cell attachment and proliferation. This novel electrospun matrix would be used as potential wound dressing for skin regeneration.
Assuntos
Quitosana/química , Álcool de Polivinil/química , Pele/fisiopatologia , Água/química , Ferimentos e Lesões , Nanoestruturas , Regeneração , SolubilidadeRESUMO
Michael addition reaction of Chitosan (CS) and polyethylene glycol diacrylate (PEGDA) was carried out successfully in acidic solution. Films with CS/PEGDA weight ratios from 100/0 to 0/100 in 10% increments were analyzed by Fourier transform infrared (FTIR) spectroscopy, Scanning Electron Microscope (SEM) and X-Ray Diffraction (XRD). Additionally, the films were characterized by measuring mechanical property, swelling property. The potential application of the CS/PEGDA film as wound dressing material was evaluated in vitro by using mouse fibroblasts (L929) as reference cell lines, indirect cytotoxicity assessment indicated that CS/PEGDA films were nontoxic to L929 cell.
Assuntos
Bandagens , Quitosana , Polietilenoglicóis , Animais , Materiais Biocompatíveis/química , Adesão Celular , Linhagem Celular Tumoral , Quitosana/química , Camundongos , Polietilenoglicóis/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In this work, a bicomponent scaffold with a core-shell and islandlike structure that combines the respective advantages of polylactic acid (PLA) and chitosan (CS) was prepared via electrospinning accompanied by automatic phase separation and crystallization. The objective of this research was to design nanosized topography with highly bioactive CS onto PLA electrospun fiber surface to improve the cell biocompatibility of the PLA fibrous membrane. The morphology, inner structure, surface composition, crystallinity, and thermodynamic analyses of nanofibers with various PLA/CS ratios were carried out, and the turning mechanism of a core-shell or islandlike topography structure was also speculated. The mineralization of hydroxyapatite and culture results of preosteoblast (MC3T3-E1) cells on the modified scaffolds indicate that the outer CS component and rough nanoscale topography on the surface of the nanofibers balanced the hydrophilicity and hydrophobicity of the fibers, enhanced their mineralization ability, and made them more beneficial for the attachment and growth of cells. Moreover, CS and "islandlike" protrusions on the fiber surface increased the alkaline phosphatase activity of the MC3T3-E1 cells seeded on the fibrous membrane and provided a more appropriate interface for cell adhesion and proliferation. These results illustrate that this kind of PLA/CS membrane has the potential in tissue engineering. More importantly, our study provides a new approach to designing PLA scaffolds, with combined topographic and bioactive modification effects at the interface between cells and materials, for biomedicine.
Assuntos
Nanofibras , Animais , Proliferação de Células , Quitosana , Camundongos , Poliésteres , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Nanoscale metal-organic frameworks (nMOF) materials represent an attractive tool for various biomedical applications. Due to the chemical versatility, enormous porosity, and tunable degradability of nMOFs, they have been adopted as carriers for delivery of imaging and/or therapeutic cargos. However, the relatively low stability of most nMOFs has limited practical in vivo applications. Here we report the production and characterization of an intrinsically radioactive UiO-66 nMOF (89Zr-UiO-66) with incorporation of positron-emitting isotope zirconium-89 (89Zr). 89Zr-UiO-66 was further functionalized with pyrene-derived polyethylene glycol (Py-PGA-PEG) and conjugated with a peptide ligand (F3) to nucleolin for targeting of triple-negative breast tumors. Doxorubicin (DOX) was loaded onto UiO-66 with a relatively high loading capacity (1 mg DOX/mg UiO-66) and served as both a therapeutic cargo and a fluorescence visualizer in this study. Functionalized 89Zr-UiO-66 demonstrated strong radiochemical and material stability in different biological media. Based on the findings from cellular targeting and in vivo positron emission tomography (PET) imaging, we can conclude that 89Zr-UiO-66/Py-PGA-PEG-F3 can serve as an image-guidable, tumor-selective cargo delivery nanoplatform. In addition, toxicity evaluation confirmed that properly PEGylated UiO-66 did not impose acute or chronic toxicity to the test subjects. With selective targeting of nucleolin on both tumor vasculature and tumor cells, this intrinsically radioactive nMOF can find broad application in cancer theranostics.
Assuntos
Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Compostos Radiofarmacêuticos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular , Linhagem Celular Tumoral , Meios de Contraste/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Liberação Controlada de Fármacos , Feminino , Humanos , Estruturas Metalorgânicas/toxicidade , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular , Peptídeos/química , Polietilenoglicóis/química , Tomografia por Emissão de Pósitrons , Radioisótopos/química , Distribuição Tecidual , Zircônio/químicaRESUMO
In this study, a hybrid photopolymeric bioadhesive system consisting of urethane methacrylated dextran (Dex-U) and 3, 4-Dihydroxyphenyl-l-alanine (DOPA) modified three-arm poly (ethylene glycol) s (PEG-DOPAs) was designed. The process of photopolymerization was detected by Photo-Differential Scanning Calorimetry (Photo-DSC). The adhesion strength was evaluated by the lap shear tests. The surface tension of the solutions, burst pressures and the cytotoxicity assays were also investigated. The addition of PEG-DOPAs significantly improved the properties of Dex-U especially in the field of adhesion strength and burst pressure. And materials variation could be tailored to match the demands for tissue repair. Compared to the Dex-U systems, the maximum adhesion strength of the copolymeric system increased from 2.7±0.1 MPa to 4.0±0.6 MPa. Owing to its strong adhesion strength, rapid curing rate and good biocompatibility, such photocrosslinkable hydrogelsa could be applied to the areas of bioadhesive.
Assuntos
Materiais Biomiméticos/síntese química , Dextranos/química , Polietilenoglicóis/química , Adesivos Teciduais/síntese química , Adesividade/efeitos da radiação , Reagentes de Ligações Cruzadas/síntese química , Reagentes de Ligações Cruzadas/efeitos da radiação , Dextranos/efeitos da radiação , Dureza/efeitos da radiação , Luz , Teste de Materiais , Fotoquímica/métodos , Polietilenoglicóis/efeitos da radiação , Adesivos Teciduais/efeitos da radiaçãoRESUMO
Synthetic adhesives inspired by marine mussel have attracted great attention due to its excellent water-resistance and good biocompatibility. In this study, a photocrosslinkable bioadhesive containing 3,4-Dihydroxy-l-phenylalanine (DOPA) functional group, which is central to curing mussel adhesive proteins, was prepared by ultraviolet (UV) irradiation of a new photocurable monomer ethylene glycol acrylate methacrylate-dopamine (EGAMA-DOPA) and a UV photocrosslinkable crosslinking agent poly(vinyl alcohol) (UV-PVA) derivative. The chemical structures of EGAMA-DOPA and UV-PVA were confirmed by Fourier Transform Infrared Reflection (FTIR) and (1)H NMR spectroscopy, respectively. The effects of UV light intensity, content of photoinitiator, EGAMA-DOPA and UV-PVA on the photopolymerization kinetics were studied, and the effects of the content of UV-PVA and temperature on the adhesive strength were also investigated. It was found that the higher UV light intensity, the faster polymerization rate and the higher final conversion that was the same as the trend of photoinitiator, EGAMA-DOPA and UV-PVA. And the adhesion strength measurement showed that, for gels with 30wt.% EGAMA-DOPA, the adhesion strength was obviously improved by about 150% with 3.0wt.% UV-PVA instead of pure PVA, and for gels containing 40wt.% EGAMA-DOPA, the adhesion strength sharply enhanced by 123% with increasing the content of UV-PVA from 1.0wt.% to 3.0wt.%. Cell attachment results showed good cell viability of L929 cell on the EGAMA-DOPA/UV-PVA adhesive gels. Thanks to its strong adhesion strength and good biocompatibility, such photocrosslinkable gels could be applied to the areas of biomedical field.
Assuntos
Adesivos/química , Materiais Biocompatíveis , Fotoquímica/métodos , Animais , Bivalves , Adesão Celular , Reagentes de Ligações Cruzadas , Di-Hidroxifenilalanina/química , Géis , Luz , Espectroscopia de Ressonância Magnética , Teste de Materiais , Metacrilatos/química , Camundongos , Estrutura Molecular , Polietilenoglicóis/química , Álcool de Polivinil/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Raios UltravioletaRESUMO
The catecholic amino acid 3,4-Dihydroxyphenyl-l-alanine (DOPA) is believed to be responsible for the water-resistant adhesive characteristics of mussel adhesive proteins (MAPs). In this paper, the synthesis of three-armed poly(ethylene glycol)s with dopamine endgroups (PEG-DOPAs) using acylation reaction and Michael addition reaction was described, and PEG-DOPAs was used as bioadhesive under the UV irradiation. The structures of PEG-DOPAs were characterized by FTIR, (1)H NMR spectroscopy. The adhesion properties of PEG-DOPAs were investigated and results were significantly superior to 0.05MPa of the commercially available fibrin adhesives. Moreover, the adhesive strength of PEG-DOPAs (Mw 3000) increased from 0.587MPa to 1.82MPa, PEG-DOPAs (Mw 20,000) increased from 0.338MPa to 1.92MPa with the elongation of the binding time, severally. The photopolymerization kinetic study was taken to evaluate gelation time of bioadhesive indirectly. The cytotoxicity of photocured PEG-DOPAs hydrogels for L929 cells was evaluated by the fluorescence microscopy and MTT (3-[4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; Thiazolyl blue) assay, respectively. The results showed that PEG-DOPAs were biocompatible and less cytotoxicity toward the growth of L929 cells. The swelling properties of PEG-DOPAs hydrogels were also tested. PEG-DOPAs (3000) reached swelling equilibrium within 2h at 37°C, and PEG-DOPAs (20,000) within 6h at 37°C.
Assuntos
Materiais Biomiméticos/síntese química , Materiais Biomiméticos/farmacologia , Bivalves , Polietilenoglicóis/síntese química , Polietilenoglicóis/farmacologia , Adesivos/síntese química , Adesivos/química , Adesivos/farmacologia , Adesivos/toxicidade , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/toxicidade , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Técnicas de Química Sintética , Di-Hidroxifenilalanina/química , Hidrogéis/química , Teste de Materiais , Camundongos , Processos Fotoquímicos , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Polimerização , Análise EspectralRESUMO
We developed a copolymeric bioadhesive system with the potential to be used as a tissue adhesive based on biopolymer dextran. Copolymeric hydrogels comprising a urethane dextran (Dex-U) and 2-hydroxyethyl methacrylate (HEMA) were prepared and crosslinked under the ultraviolet (UV) irradiation. In this study, the photopolymerization process was monitored by real time infrared spectroscopy (RTIR). The adhesion strength was evaluated by lap-shear-test. The surface tension, viscosity of the solutions and the cytotoxicity assays were investigated. Compared to Dex-U system, the addition of HEMA remarkably improved the properties of Dex-H system especially the adhesion strength and the nontoxicity. And materials variation could be tailored to match the need of tissues. The copolymeric tissue adhesives demonstrated promising adhesion strength and nontoxicity. The maximum adhesion strength reached to 4.33±0.47 Mpa which was 86 times higher than that of Tisseel. The obtained products have the potential to serve as tissue adhesive in the future.
Assuntos
Dextranos/química , Luz , Metacrilatos/química , Adesivos Teciduais/química , Adesividade , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Hidrogéis/química , Cinética , Camundongos , Tensão Superficial , Adesivos Teciduais/toxicidadeRESUMO
A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future.
Assuntos
Materiais Biocompatíveis/farmacologia , Reagentes de Ligações Cruzadas/química , Dextranos/química , Gelatina/química , Luz , Polímeros/farmacologia , Adesivos Teciduais , Animais , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibrossarcoma/tratamento farmacológico , Humanos , Hidrogéis/química , Espectroscopia de Ressonância Magnética , Camundongos , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
The core-shell structure nanofibers of poly(lactic acid)/chitosan with different weight ratios were successfully electrospun from homogeneous solution. The preparation process was more simple and effective than double-needle electrospinning. The nanofibers were obtained with chitosan in shell while poly(lactic acid) in core attributing to phase separation, which were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and energy dispersive spectrometer (EDS). The electrospun nanofibrous membrane was evaluated in vitro by using mouse fibroblasts (L929) as reference cell lines. Cell culture results indicated that these materials were good in promoting cell growth and attachment, thus they could be used for tissue engineering and wound healing dressing.
Assuntos
Quitosana/química , Eletroquímica , Fibroblastos/citologia , Ácido Láctico/química , Membranas Artificiais , Nanofibras/química , Polímeros/química , Animais , Adesão Celular , Células Cultivadas , Reagentes de Ligações Cruzadas/farmacologia , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Poliésteres , Espectroscopia de Infravermelho com Transformada de Fourier , Engenharia Tecidual , Difração de Raios XRESUMO
Novel biodegradable hydrogels by photocrosslinking macromers based on chitosan derivative are reported. Photocrosslinkable macromers, a water-soluble (methacryloyloxy) ethyl carboxyethyl chitosan were prepared by Michael-addition reaction between chitosan and ethylene glycol acrylate methacrylate. The macromers were characterized by Fourier transform infrared spectroscopy, (1)H NMR and (13)C NMR. Hydrogels were fabricated by exposing aqueous solutions of macromers with 0.1% (w/v) photoinitiator to UV light irradiation, and their swelling kinetics as well as degradation behaviors was evaluated. The results demonstrated that the degradation rates were affected strongly by crosslinking density. The hydrogel was compatible to Vero cells, not exhibiting significant cytotoxicity. Cell culture assay also demonstrated that the hydrogels were good in promoting the cell attachment and proliferation, showing their potential as tissue engineering scaffolds.