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1.
Biomacromolecules ; 24(12): 5977-5988, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-37939799

RESUMEN

Two-dimensional (2D) cell culture methods dominate the current research. However, the inherent responsiveness of cells to their native three-dimensional (3D) microenvironment necessitates a paradigm shift toward the development of advanced hydrogels that faithfully mimic the intricacies of the extracellular matrix (ECM) and enable continuous cell-ECM interactions. To address the constraints of traditional static hydrogel networks that impede effective cell-matrix and cell-cell interactions, and to tackle the inherent stability issues associated with dynamically cross-linked hydrogels, which have become a pressing concern. Herein, we present an interpenetrating polymer network (IPN) hydrogel (HA/Alg-RGD hydrogel) that combines a physically cross-linked network between alginate and calcium ions (Alg-Ca2+) for the enhanced cell growth adaptability with a chemically cross-linked hyaluronic acid (HA) network to ensure macroscopic stability during cell culture. The incorporation of arginine-glycine-aspartic peptide modified alginate (Alg-RGD) further facilitates cell adhesion and improves the cell-hydrogel interaction. Notably, this IPN hydrogel demonstrates mechanical stability and enables cell spreading and growth within its structural framework. Leveraging the reversible characteristics of the ionically cross-linked Alg-Ca2+ network within IPN hydrogels, we demonstrate the feasibility of the gelatin sacrificial solution for 3D printing purposes within the hydrogel matrix. Subsequent UV-induced covalent cross-linking enables the fabrication of vascularized microfluidic channels within the resulting construct. Our results demonstrate endothelial cell spreading and spontaneous cell sprouting within the hydrogel matrix, thus highlighting the efficacy of this IPN hydrogel system in facilitating 3D cell growth. Additionally, our study emphasizes the potential of 3D printed constructs as a promising approach for vascularization in tissue engineering. The importance of RGD peptides in promoting favorable cell-hydrogel scaffold interactions is also highlighted, emphasizing their critical role in optimizing biomaterial-cell interfaces.


Asunto(s)
Ácido Hialurónico , Polímeros , Ácido Hialurónico/química , Hidrogeles/farmacología , Hidrogeles/química , Ingeniería de Tejidos/métodos , Alginatos/química , Impresión Tridimensional , Oligopéptidos , Andamios del Tejido
2.
Biomacromolecules ; 22(12): 5097-5107, 2021 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-34723499

RESUMEN

Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.


Asunto(s)
Cartílago Articular , Hidrogeles , Animales , Celulosa/farmacología , Ácido Hialurónico , Hidrogeles/farmacología , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos
3.
Mol Pharm ; 15(11): 4814-4826, 2018 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-30222933

RESUMEN

Chitosan has been widely employed to deliver nucleic acids such as siRNA and plasmids. However, chitosan-mediated delivery of a gene-editing system has not been reported yet. In this study, poly(ethylene glycol) monomethyl ether (mPEG) was conjugated to chitosan with different molecular weights (low molecular weight and medium molecular weight chitosan) achieving a high degree of substitution as identified by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR) spectra. PEGylated chitosan/pSpCas9-2A-GFP nanocomplexes were formed at different N/ P (amine group to phosphate group) ratios and characterized in terms of size and zeta potential. The nanocomplexes developed showed the capability to protect loaded nucleic acids from DNase I digestion and from the stresses of nebulization. In addition, we demonstrated that the PEG conjugation of chitosan improved the mucus-penetration capability of the formed nanocomplexes at N/ P ratios of 5, 10, 20, and 30. Finally, PEGylated low molecular weight chitosan nanocomplexes showed optimal transfection efficiency at an N/ P ratio of 20, while PEGylated medium molecular weight chitosan nanocomplexes showed an optimal transfection efficiency at an N/ P ratio of 5 at pH 6.5 and 6.8. This study established the basis for the delivery of a gene-editing system by PEGylated chitosan nanocomplexes.


Asunto(s)
Sistemas CRISPR-Cas/genética , ADN/administración & dosificación , Edición Génica/métodos , Nanoestructuras/química , Transfección/métodos , Administración por Inhalación , Quitosano/química , Estudios de Factibilidad , Edición Génica/instrumentación , Células HEK293 , Humanos , Nebulizadores y Vaporizadores , Polietilenglicoles/química , Transfección/instrumentación
4.
Macromol Rapid Commun ; 39(14): e1700872, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29573008

RESUMEN

Three novel copolymers based on zigzag naphthodithiophene (zNDT) with different aromatic rings as π bridges and different core side substitutions are designed and synthesized (PzNDT-T-1,3-bis(4-(2-ethylhexyl)-thiophen-2-yl)-5,7-bis(2-ethylhexyl)benzo[1,2-c:4,5-c']-dithiophene-4,8-dione (BDD), PzNDT-TT-BDD, and PzNDTP-T-BDD, respectively). The 2D conjugation structure and molecular planarity of the polymers can be effectively altered through the modification of conjugated side chains and π-bridges. These alterations contribute to the variation in energy levels, light absorption capacity, and morphology compatibility of the polymers. When blended with the nonfullerene acceptor (2,2'-[(4,4,9,9-tetrahexyl-4,9-dihydro-sindaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis[methylidyne(3-oxo-1H-indene-2,1(3H)-diylidene)]]bis-propanedinitrile) (IDIC), PzNDT-T-BDD exhibits the highest power conversion efficiency (PCE) of 9.72% among the three polymers. This result can be attributed to its superior crystallinity and more obvious face-on orientation in blending film. PzNDT-TT-BDD and PzNDTP-T-BDD present PCE values of 8.20% and 4.62%, respectively. The alteration of polymer structure, particularly the modification of conjugated side chains and π-bridges, is an effective strategy for designing NDT-based polymers with high photovoltaic performance and potential applications in fullerene-free solar cells.


Asunto(s)
Fulerenos/química , Polímeros/química , Energía Solar , Tiofenos/química
5.
Environ Geochem Health ; 40(6): 2441-2452, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29691784

RESUMEN

Concentrations of eight trace metals (TMs) in road dust (RD) (particles < 25 µm) from urban areas of Xinxiang, China, were determined by inductively coupled plasma mass spectrometry. The geometric mean concentrations of Zn, Mn, Pb, As, Cu, Cr, Ni and Cd were 489, 350, 114, 101, 60.0, 39.7, 31.6, and 5.1 mg kg-1, respectively. When compared with TM levels in background soil, the samples generally display elevated TM concentrations, except for Cr and Mn, and for Cd the enrichment value was 69.6. Spatial variations indicated TMs in RD from park path would have similar sources with main roads, collector streets and bypasses. Average daily exposure doses of the studied TMs were about three orders of magnitude higher for hand-to-mouth ingestion than dermal contact, and the exposure doses for children were 9.33 times higher than that for adults. The decreasing trend of calculated hazard indexes (HI) for the eight elements was As > Pb > Cr > Mn > Cd > Zn > Ni > Cu for both children and adults.


Asunto(s)
Arsénico/análisis , Polvo/análisis , Monitoreo del Ambiente , Metales Pesados/análisis , Oligoelementos/análisis , China , Ciudades , Humanos , Tamaño de la Partícula , Medición de Riesgo
6.
J Sep Sci ; 37(5): 587-94, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24376214

RESUMEN

An IPC-imprinted (IPC is isoprocarb) poly(methacrylic acid)/SiO2 hybrid monolithic column was prepared and applied for the recognition of the template. The hybrid monolithic column was synthesized in a micropipette tip using methyltrimethoxysilane as the inorganic precursor, 3-(methacryloxy)propyltrimethoxysilane as the coupling agent, and ethylene glycol dimethacrylate as the cross-linker. The synthesis conditions, including the porogenic solvent, coupling agent, volume ratio of the inorganic alcoholysate and organic part, were optimized. The prepared monolithic column was characterized by SEM and FTIR spectroscopy. A simple, rapid, and sensitive method for the determination of IPC in rice using the imprinted monolithic column microextraction combined with HPLC was developed. Several parameters affecting the sample pretreatment were investigated, including the eluent, washing solution, and loading sample volume. The linearity of the calibration curve was observed in the range of 9.0-1000 µg/kg for IPC in rice with the correlation coefficient (r2) of 0.9983. The LOD was 3.0 µg/kg (S/N = 3). The assay gave recovery values ranging from 91 to 107%. The proposed method has been successfully applied for the selective extraction and sensitive determination of IPC in rice and a satisfactory result was obtained.


Asunto(s)
Carbamatos/análisis , Carbamatos/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Insecticidas/análisis , Insecticidas/aislamiento & purificación , Oryza/química , Polímeros/química , Extracción en Fase Sólida/métodos , Contaminación de Alimentos/análisis , Impresión Molecular , Polímeros/síntesis química , Extracción en Fase Sólida/instrumentación
7.
J Hazard Mater ; 470: 134152, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38552398

RESUMEN

Soil contamination by emerging pollutants tetrabromobisphenol A (TBBPA) and microplastics has become a global environmental issue in recent years. However, little is known about the effect of microplastics on degradation of TBBPA in soil, especially aged microplastics. In this study, the effect of aged polystyrene (PS) microplastics on the degradation of TBBPA in soil and the mechanisms were investigated. The results suggested that the aged microplastics exhibited a stronger inhibitory effect on the degradation of TBBPA in soil than the pristine microplastics, and the degradation efficiency of TBBPA decreased by 21.57% at the aged microplastic content of 1%. This might be related to the higher TBBPA adsorption capacity of aged microplastics compared to pristine microplastics. Aged microplastics strongly altered TBBPA-contaminated soil properties, reduced oxidoreductase activity and affected microbial community composition. The decrease in soil oxidoreductase activity and relative abundance of functional microorganisms (e.g., Bacillus, Pseudarthrobacter and Sphingomonas) caused by aged microplastics interfered with metabolic pathways of TBBPA. This study indicated the importance the risk assessment and soil remediation for TBBPA-contaminated soil with aged microplastics.


Asunto(s)
Biodegradación Ambiental , Microplásticos , Bifenilos Polibrominados , Poliestirenos , Microbiología del Suelo , Contaminantes del Suelo , Poliestirenos/química , Bifenilos Polibrominados/toxicidad , Microplásticos/toxicidad , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/química , Oxidorreductasas/metabolismo , Suelo/química , Adsorción
8.
ACS Appl Bio Mater ; 6(6): 2295-2302, 2023 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-37204306

RESUMEN

Methods of DNA cleavage have broad bioapplications in gene editing, disease treatment, and biosensor design. The traditional method for DNA cleavage is mainly through oxidation or hydrolysis mediated by small molecules or transition metal complexes. However, DNA cleavage by artificial nucleases using organic polymers has been rarely reported. Methylene blue has been extensively studied in the fields of biomedicine and biosensing due to its excellent singlet oxygen yield, redox properties, and good DNA affinity. Methylene blue mainly relies on light and oxygen for DNA cleavage, and the cutting rate is slow. Here, we synthesize cationic methylene-blue-backboned polymers (MBPs) that can bind DNA efficiently and induce DNA cleavage through free radical mechanisms in the absence of light and exogenous reagents, showing high-efficiency nuclease activity. In addition, MBPs with different structures showed selectivity for DNA cleavage, and the cleavage efficiency of the flexible structure was significantly higher than that of the rigid structure. Studies on the DNA cleavage mechanism have shown that the cleavage mechanism of MBPs is not through the common ROS-mediated oxidative cleavage pathway, but through the radical of MBP• inducing DNA cleavage. Meanwhile, MBPs can simulate topoisomerase I (Topo I)-mediated topological rearrangement of superhelical DNA. This work paved a way for the application of MBPs in the field of artificial nucleases.


Asunto(s)
Complejos de Coordinación , Azul de Metileno , Azul de Metileno/farmacología , División del ADN , Polímeros , Complejos de Coordinación/química , ADN/química
9.
Environ Sci Pollut Res Int ; 30(38): 88272-88280, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37440140

RESUMEN

Air pollution and global temperature change are expected to affect infectious diseases. Air pollution usually causes inflammatory response and disrupts immune defense system, while temperature mainly exacerbates the effect of vectors on humans. Yet to date overview of systematic reviews assessing the exposure risk of air pollutants and temperature on infectious diseases is unavailable. This article aims to fill this research gap. PubMed, Embase, the Cochrane Library, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature were searched. Systematic reviews and meta-analyses investigated the exposure risk of pollutants or temperature on infectious diseases were included. Two investigators screened literature, extracted data and performed the risk of bias assessments independently. A total of 23 articles met the inclusion criteria, which 3 (13%) were "low" quality and 20 (87%) were "critically low" quality. COVID-19 morbidity was associated with long-term exposure PM2.5 (RR = 1.056 per 1 [Formula: see text], 95% CI: 1.039-1.072) and NO2 (RR = 1.042 per 1 [Formula: see text], 95% CI: 1.017-1.068). In addition, for each 1 °C increase in temperature, the morbidity risk of dengue increased 13% (RR = 1.130 per 1 °C, 95% CI: 1.120-1.150), infectious diarrhea increased 8% (RR = 1.080 per 1 °C, 95% CI: 1.050-1.200), and hand, foot and mouth disease (HFMD) increased 5% (RR = 1.050 per 1 °C, 95% CI: 1.020-1.080). In conclusion, PM2.5 and NO2 increased the risk of COVID-19 and temperatures were associated with dengue, infectious diarrhoea and HFMD morbidity. Moreover, the exposure risk of temperature on COVID-19 was recommended to be further explored.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Enfermedades Transmisibles , Dengue , Humanos , Temperatura , Dióxido de Nitrógeno/análisis , Biodiversidad , Exposición a Riesgos Ambientales/análisis , COVID-19/epidemiología , Revisiones Sistemáticas como Asunto , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Medición de Riesgo , Material Particulado/análisis , Enfermedades Transmisibles/epidemiología
10.
Food Chem ; 424: 136428, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37247595

RESUMEN

The regulatory mechanisms underlying the salicylic acid (SA)-mediated inhibition of senescence in pummelo fruit, the largest known citrus variety, remain unclear. Herein, postharvest 0.3% SA treatment was demonstrated to delay postharvest 'Jinshayou' pummelo senescence, as evidenced by the inhibitions in firmness loss, electrolyte leakage increase, and color change. Using comparative transcriptomic data, a total of 4367, 3769, and 1659 DEGs were identified between CK0 and CK60, CK0 and SA60, and CK60 and SA60, respectively. Further GO analysis revealed that DEGs were mainly implicated in the processes of cell wall modification and phenylpropanoid pathway during fruit senescence. More importantly, postharvest exogenous 0.3% SA treatment was observed to inhibit CWDEs activities and their encoding gene expression, retain higher protopectin, cellulose, and hemicelluloses contents, as well as reduce WSP content, thus maintaining cell wall structure. These findings collectively indicated that postharvest SA treatment was a green and useful preservative for alleviating fruit senescence and prolonging the storage life of harvested 'Jiashayou' pummelo fruit.


Asunto(s)
Citrus , Citrus/química , Transcriptoma , Ácido Salicílico/metabolismo , Celulosa/metabolismo , Pared Celular/química , Frutas/química
11.
Environ Pollut ; 334: 122156, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37422085

RESUMEN

Microplastics, a kind of emerging pollutant, have become a global environmental research hotspot in recent years due to its wide distribution in soil and its impact on soil ecosystems. However, little information is available on the interactions between microplastics and organic contaminants in soil, especially after microplastic aging. The impact of polystyrene (PS) microplastic aging on the sorption of tetrabromobisphenol A (TBBPA) in soil and the desorption characteristics of TBBPA-loaded microplastics in different environments were studied. The results showed a significant increase of 76.3% in adsorption capacity of TBBPA onto PS microplastics after aging for 96 h. Based on the results of characterization analysis and density functional theory (DFT) calculation, the mechanisms of TBBPA adsorption changed mainly from hydrophobic and π-π interactions on pristine PS microplastics to hydrogen bond and π-π interactions on aged PS microplastics. The presence of PS microplastics increased the TBBPA sorption capacity onto soil-PS microplastics system and significantly altered the distribution of TBBPA on soil particles and PS microplastics. The high TBBPA desorption over 50% from aged PS microplastics in simulated earthworm gut environment suggested that TBBPA contamination combined with PS microplastics might pose a higher risk to macroinvertebrates in soil. Overall, these findings contribute to the understanding of impact of PS microplastic aging in soil on the environmental behaviors of TBBPA, and provide valuable reference for evaluating the potential risk posed by the co-existence of microplastics with organic contaminants in soil ecosystems.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Poliestirenos , Plásticos , Adsorción , Suelo/química , Disponibilidad Biológica , Ecosistema , Contaminantes Químicos del Agua/análisis
12.
J Mater Chem B ; 11(25): 5830-5845, 2023 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-37283547

RESUMEN

Fabricating an organic-inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague-Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues.


Asunto(s)
Antibacterianos , Osteogénesis , Ratas , Animales , Nanogeles , Antibacterianos/farmacología , Ratas Sprague-Dawley , Bacterias Gramnegativas , Bacterias Grampositivas , Durapatita/química , Colágeno/química , Antiinflamatorios/farmacología , Inflamación , Hidrogeles/farmacología
13.
Sci Data ; 9(1): 515, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35999222

RESUMEN

The somatotopic representation of the body is a well-established organizational principle in the human brain. Classic invasive direct electrical stimulation for somatotopic mapping cannot be used to map the whole-body topographical representation of healthy individuals. Functional magnetic resonance imaging (fMRI) has become an indispensable tool for the noninvasive investigation of somatotopic organization of the human brain using voluntary movement tasks. Unfortunately, body movements during fMRI scanning often cause large head motion artifacts. Consequently, there remains a lack of publicly accessible fMRI datasets for whole-body somatotopic mapping. Here, we present public high-resolution fMRI data to map the somatotopic organization based on motor movements in a large cohort of healthy adults (N = 62). In contrast to previous studies that were mostly designed to distinguish few body representations, most body parts are considered, including toe, ankle, leg, finger, wrist, forearm, upper arm, jaw, lip, tongue, and eyes. Moreover, the fMRI data are denoised by combining spatial independent component analysis with manual identification to clean artifacts from head motion associated with body movements.


Asunto(s)
Imagen por Resonancia Magnética , Corteza Motora , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico/métodos , Cuerpo Humano , Humanos , Imagen por Resonancia Magnética/métodos , Corteza Motora/fisiología
14.
Chemosphere ; 306: 135573, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35797912

RESUMEN

The pollution of microplastics (MPs) in soil has become a global environmental problem. Due to high sorption capacity and persistence in environment, the MPs exhibit combined effects with organic pollutants in soil, thereby posing a potential risk to soil ecology and human health. However, limited reviews are available on this subject. Therefore, in response to this issue, this review provides an in-depth account of interaction of MPs with organic contaminants in soil and the combined risks to soil environment. The sorption of organic contaminants onto MPs is mainly through hydrophobic and π-π interactions, hydrogen bonding, pore filling and electrostatic and van der Waals forces. The intrinsic characteristics of MPs, organic contaminants and soil are the key factors influencing the sorption of organic pollutants onto MPs. Importantly, the presence of MPs changes the sorption, degradation and transport behaviors of organic contaminants in soil, and affects the toxic effects of organic contaminants on soil organisms including animals, plants and soil microorganisms through synergistic or antagonistic effects. Source control, policy implementation and plastic removal are the main preventive and control measures to reduce soil MPs pollution. Finally, priorities for future research are proposed, such as field investigations of co-pollution, contribution of plastisphere to organic contaminant degradation, and mechanisms of MPs effects on organic contaminant toxicity.


Asunto(s)
Contaminantes Ambientales , Contaminantes Químicos del Agua , Animales , Humanos , Microplásticos , Plásticos/química , Suelo , Contaminantes Químicos del Agua/análisis
15.
Int J Pharm ; 605: 120831, 2021 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-34175380

RESUMEN

Gene therapy and more recently, gene editing is attractive via pulmonary delivery for enhanced regional targeting. However, processing of sensitive therapeutics into dry powders for inhalation can be problematic due to relatively stressful spraying or milling steps. Thin-film freeze-drying (TFFD) has attracted attention with its promising application in the production of DPI formulations possessing respirable particle size range (1-5 µm) particularly for thermally or shear sensitive therapeutics. In this study, gene editing dry powder formulations containing PEGylated chitosan/CRISPR-Cas9 nanocomplexes were prepared by TFFD. To evaluate stability during processing, nanocomplex size, zeta potential and transfection efficiency of reconstituted formulations were evaluated, and six potential DPI formulations were identified and characterized in terms of geometric particle size, powder surface morphology, and crystallinity. It was found that two formulations containing 3% mannitol with or without leucine were identified as suitable for inhalation with a desired aerodynamic performance. The flow rate dependency and inhaler dependency of these two formulations were also evaluated at different flow rates (60 L/min and 45 L/min) and different inhaler devices (RS01 DPI and HandiHaler) using NGI testing. This study demonstrated that TFFD processing of CRISPR-Cas9 polymer nanocomplexes resulted in a suitable dry powder for inhalation.


Asunto(s)
Quitosano , Administración por Inhalación , Aerosoles , Sistemas CRISPR-Cas , Inhaladores de Polvo Seco , Tamaño de la Partícula , Polietilenglicoles , Polvos
16.
ACS Appl Bio Mater ; 4(12): 8597-8606, 2021 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-35005952

RESUMEN

Artificial small-diameter blood vessels (SDBVs) are extremely limited in their thrombosis and still present significant clinical challenges worldwide. In recent years, 3D-bio-printing has offered a powerful technique to fabricate vessel channels in tissue engineering applications. Hydrogels are attractive bio-inks for SDBVs 3D-bio-printing, but they usually present weak mechanical properties. To overcome the weak mechanical properties of hydrogel bio-inks, a printable human umbilical vein endothelial cell (HUVEC)-laden polyrotaxane-alginate (PR-Alg) double-network (DN) hydrogel was fabricated. The PR-Alg DN hydrogel consists of a Ca2+ cross-linked alginate network to form the first network rapidly, and a photo-cross-linked slide-ring network was designed as the second network. By combining special hydrogel structures of slide-ring (SR) and double network (DN), we significantly improved the mechanical properties of hydrogels. The PR-Alg DN hydrogel provides excellent stress (199 ± 20 kPa) and strain (1239 ± 58%), and the fracture energy reaches 668 ± 80 J/m2. Additionally, due to the presence of biocompatible materials and the gentle 3D-bio-printing process, the 3D-bio-printed channels showed outstanding biocompatibility, particularly in HUVECs' survival and proliferation. We anticipate that this work will expand the application of hydrogels with improved mechanical properties in biomedicine, particularly for artificial SDBVs.


Asunto(s)
Hidrogeles , Impresión Tridimensional , Alginatos/farmacología , Materiales Biocompatibles/farmacología , Humanos , Hidrogeles/farmacología , Ingeniería de Tejidos/métodos
17.
ACS Appl Bio Mater ; 4(1): 406-419, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-35014292

RESUMEN

The success of complex tissue and internal organ reconstruction relies principally on the fabrication of a 3D vascular network, which guarantees the delivery of oxygen and nutrients in addition to the disposal of waste. In this study, a rapidly forming cell-encapsulated double network (DN) hydrogel is constructed by an ultrasonically activated silk fibroin network and bioorthogonal-mediated polyethylene glycol network. This DN hydrogel can be solidified within 10 s, and its mechanical property gradually increases to ∼20 kPa after 30 min. This work also demonstrates that coencapsulation of human umbilical vein endothelial cells (HUVECs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) into the DN hydrogel can facilitate the formation of more mature vessels and complete the capillary network in comparison with the hydrogels encapsulated with a single cell type both in vitro and in vivo. Taking together, the DN hydrogel, combined with coencapsulation of HUVECs and UCMSCs, represents a strategy for the construction of a functional vascular network.


Asunto(s)
Fibroínas/química , Hidrogeles/química , Polietilenglicoles/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Módulo de Elasticidad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Cordón Umbilical/citología
18.
Nanoscale ; 12(28): 14976-14995, 2020 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-32644089

RESUMEN

Tissue engineering is an important field of regenerative medicine, which combines scaffolds and cell transplantation to develop substitute tissues and/or promote tissue regeneration. Hydrogels, a three-dimensional network with high water content and biocompatibility, have been widely used as scaffolds to mimic the structure and properties of tissues. However, the low mechanical strength and limited functions of traditional hydrogels greatly limited their applications in tissue engineering. Recently, nanocomposite hydrogels, with its advantages of high mechanical property and some unique properties (such as electrical conductivity, antibacterial, antioxidation, magnetic responsiveness), have emerged as the most versatile and innovative technology, which provides a new opportunity as a unique tool for fabricating hydrogels with excellent properties. In this review, we summarize the recent advances in fabricating nanocomposite hydrogels and their applications in tissue engineering. In addition, the future and prospects of nanocomposite hydrogels for tissue engineering are also discussed.


Asunto(s)
Hidrogeles , Ingeniería de Tejidos , Conductividad Eléctrica , Nanogeles , Medicina Regenerativa , Andamios del Tejido
19.
ACS Appl Mater Interfaces ; 12(32): 35928-35939, 2020 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-32686939

RESUMEN

The design and synthesis of a novel generation of a nanoscaled platform with imaging-guided therapy remain a real challenge. It can not only improve the imaging sensitivity of tumor tissues for guiding all kinds of treatments but also reduce the harm for healthy tissues. Here, polydopamine (PDA), polyethylene glycol (PEG), and c(RGDyK) peptide (RGD)-modified and cisplatin-loaded Gd2Hf2O7 nanoparticles (Gd2Hf2O7@PDA@PEG-Pt-RGD NPs) are designed for magnetic resonance imaging (MRI)-guided combined chemo-/photothermal-/radiotherapy of resistant tumors. The as-prepared NPs display high relaxivity (r1 = 38.28 mM-1 s-1) as an MRI contrast agent because of their ultrasmall size and surface modification with polyacrylic acid and PDA. Gd2Hf2O7@PDA@PEG-Pt-RGD NPs exhibit pH and NIR dual-stimuli responsiveness for cisplatin release. Based on competent NIR absorption and high X-ray attenuation efficiency, Gd2Hf2O7@PDA@PEG-Pt-RGD NPs show potential photothermal effect by exposing to an 808 nm NIR laser and significantly improve the generation of reactive oxygen species after X-ray radiation. Combined chemo-/photothermal-/radiotherapy can effectively treat the resistant A549R cells, providing the enhanced therapeutic efficiency to cancer tissues and the reduced side effect to healthy tissues. Furthermore, Gd2Hf2O7@PDA@PEG-Pt-RGD NPs present no obvious toxicity during the treatment, which demonstrates the potential as an efficient MRI-guided combined chemo-/photothermal-/radiotherapy nanoplatform for drug-resistant tumors.


Asunto(s)
Antineoplásicos/química , Medios de Contraste/química , Gadolinio/química , Hafnio/química , Nanopartículas del Metal/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Óxidos/química , Animales , Antineoplásicos/farmacología , Cisplatino/química , Cisplatino/farmacología , Terapia Combinada , Portadores de Fármacos/química , Liberación de Fármacos , Resistencia a Antineoplásicos , Quimioterapia , Femenino , Humanos , Hipertermia Inducida , Indoles/química , Integrinas/metabolismo , Imagen por Resonancia Magnética , Ratones , Ratones Desnudos , Oligopéptidos/química , Terapia Fototérmica , Polietilenglicoles/química , Polímeros/química , Radioterapia , Especies Reactivas de Oxígeno/metabolismo , Propiedades de Superficie
20.
J Mater Chem B ; 8(27): 5845-5848, 2020 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-32667029

RESUMEN

An injectable BMSC-encapsulated double network (DN) hydrogel was fabricated via silk fibroin (SF) and poly(ethylene glycol) (PEG), which could efficiently support the survival and proliferation of BMSCs in vitro as well as cartilage repair in vivo, and provides a new strategy for cartilage tissue engineering.


Asunto(s)
Materiales Biocompatibles/química , Cartílago/metabolismo , Fibroínas/química , Hidrogeles/química , Polietilenglicoles/química , Andamios del Tejido/química , Animales , Condrogénesis , Humanos , Ratas , Ratas Sprague-Dawley
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