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1.
Proc Natl Acad Sci U S A ; 120(39): e2307816120, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37725650

RESUMEN

Hydrogel adhesion that can be easily modulated in magnitude, space, and time is desirable in many emerging applications ranging from tissue engineering and soft robotics to wearable devices. In synthetic materials, these complex adhesion behaviors are often achieved individually with mechanisms and apparatus that are difficult to integrate. Here, we report a universal strategy to embody multifaceted adhesion programmability in synthetic hydrogels. By designing the surface network topology of a hydrogel, supramolecular linkages that result in contrasting adhesion behaviors are formed on the hydrogel interface. The incorporation of different topological linkages leads to dynamically tunable adhesion with high-resolution spatial programmability without alteration of bulk mechanics and chemistry. Further, the association of linkages enables stable and tunable adhesion kinetics that can be tailored to suit different applications. We rationalize the physics of polymer chain slippage, rupture, and diffusion at play in the emergence of the programmable behaviors. With the understanding, we design and fabricate various soft devices such as smart wound patches, fluidic channels, drug-eluting devices, and reconfigurable soft robotics. Our study presents a simple and robust platform in which adhesion controllability in multiple aspects can be easily integrated into a single design of a hydrogel network.

2.
J Enzyme Inhib Med Chem ; 39(1): 2289355, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38059332

RESUMEN

Liver cancer exhibits a high degree of heterogeneity and involves intricate mechanisms. Recent research has revealed the significant role of histone lysine methylation and acetylation in the epigenetic regulation of liver cancer development. In this study, five inhibitors capable of targeting both histone lysine methyltransferase nuclear receptor-binding SET domain 2 (NSD2) and histone deacetylase 2 (HDAC2) were identified using a structure-based virtual screening approach. Notably, DT-NH-1 displayed a potent inhibition of NSD2 (IC50 = 0.08 ± 0.03 µM) and HDAC2 (IC50 = 5.24 ± 0.87 nM). DT-NH-1 also demonstrated a strong anti-proliferative activity against various liver cancer cell lines, particularly HepG2 cells, and exhibited a high level of biological safety. In an experimental xenograft model involving HepG2 cells, DT-NH-1 showed a significant reduction in tumour growth. Consequently, these findings indicate that DT-NH-1 will be a promising lead compound for the treatment of liver cancer with epigenetic dual-target inhibitors.


Asunto(s)
Neoplasias Hepáticas , Simulación de Dinámica Molecular , Humanos , Epigénesis Genética , Histona Desacetilasa 2/metabolismo , Detección Precoz del Cáncer , Neoplasias Hepáticas/tratamiento farmacológico , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química
3.
Molecules ; 27(17)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36080431

RESUMEN

The CRISPR-Cas system is a bacterial and archaea adaptive immune system and is a newly recognized mechanism for controlling antibiotic resistance gene transfer. Acinetobacter baumannii (A. baumannii) is an important organism responsible for a variety of nosocomial infections. A. baumannii infections have become problematic worldwide because of the resistance of A. baumannii to multiple antibiotics. Thus, it is clinically significant to explore the relationship between the CRISPR-Cas system and drug resistance in A. baumannii. This study aimed to analyze the genomic characteristics of the A. baumannii strain AB3 containing the type I-Fb CRISPR-Cas system, which was isolated from a tertiary care hospital in China, and to investigate the relationship between the CRISPR-Cas system and antibiotic resistance in this strain. The whole-genome sequencing (WGS) of the AB43 strain was performed using Illumina and PacBio sequencing. The complete genome of AB43 consisted of a 3,854,806 bp chromosome and a 104,309 bp plasmid. The specific characteristics of the CRISPR-Cas system in AB43 are described as follows: (1) The strain AB43 carries a complete type I-Fb CRISPR-Cas system; (2) Homology analysis confirmed that the cas genes in AB43 share high sequence similarity with the same subtype cas genes; (3) A total of 28 of 105 A. baumannii AB43 CRISPR spacers matched genes in the bacteriophage genome database and the plasmid database, implying that the CRISPR-Cas system in AB43 provides immunity against invasive bacteriophage and plasmids; (4) None of the CRISPR spacers in A. baumannii AB43 were matched with antimicrobial resistance genes in the NCBI database. In addition, we analyzed the presence of antibiotic resistance genes and insertion sequences in the AB43 strain and found that the number of antibiotic resistance genes was not lower than in the "no CRISPR-Cas system" strain. This study supports the idea that the CRISPR-Cas system may inhibit drug-resistance gene expression via endogenous gene regulation, except to the published mechanism that the CRISPR-Cas system efficiently limits the acquisition of antibiotic resistance genes that make bacteria sensitive to antibiotics.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Infecciones por Acinetobacter/microbiología , Antibacterianos/farmacología , Bacterias , Resistencia a Medicamentos , Farmacorresistencia Bacteriana Múltiple , Genoma Bacteriano , Humanos
4.
Molecules ; 27(13)2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35807422

RESUMEN

To verify the size and emergence time of new permeability pathways (NPPs) in malaria parasites, the permeability of the Plasmodium falciparum-infected erythrocytes was tested with different particle sizes of nanomaterials by flow cytometry assay. The results confirmed the permeability of the host cell membrane increases with parasite maturation for the stage-development evolution of NPPs, and especially found that a particle size of about 50 nm had higher efficiency. As a kind of the novel nanomaterials, nitrogen-doped carbon dots (NCDs) showed no toxicity, specificity binding ability to the malaria parasites, and could label live elder blood-stage P. falciparum through NPPs, indicating the potential application in cell imaging. NPPs and some nanomaterials such as NCDs deserve more attention and exploration for the elimination and prevention of malaria.


Asunto(s)
Malaria Falciparum , Malaria , Humanos , Carbono/metabolismo , Permeabilidad de la Membrana Celular , Eritrocitos/parasitología , Malaria/metabolismo , Malaria Falciparum/parasitología , Nitrógeno/metabolismo , Permeabilidad , Plasmodium falciparum
5.
Foodborne Pathog Dis ; 11(7): 503-10, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24824113

RESUMEN

To understand the intrinsic links and epidemic features of Staphylococcus aureus, isolates of this bacterium were collected from different origins in China. A total of 503 isolates from different sources were tested for the presence of methicillin-resistant Staphylococcus aureus (MRSA) and types of staphylococcal cassette chromosome mec (SCCmec) elements. Of these isolates, 250 were analyzed by multilocus sequence typing (MLST). Results showed that MRSA isolates account for 21.67% and have five types. SCCmec type I, II, and III isolates were all from humans, while SCCmec type IV, V, and untypeable MRSA isolates were from clinical origin, pigs, raw milk, or environments. The results by MLST showed considerable molecular heterogeneity in 52 different sequence types (STs) including 16 novel STs, which yielded 7 clonal complexes (CCs) and 5 doublets (Ds). The results from these analyses showed that hospital-acquired MRSA (HA-MRSA), rather than community-associated MRSA (CA-MRSA), remained the major pathogenic bacterium in the clinical setting. CA-MRSA infections have been increasing and forming new pandemic clones. CC630, CC239, D9, and D398 were important clones in this study. CC630 was a new epidemic CA clone circulating among humans, environments, and animals. CC239 was a HA-MRSA-III pandemic clone of clinical origin. The D9 clone was a livestock-associated (LA) clone, which up to now, has spread only in livestock and has not been found in humans that live in Jiangsu province. In Europe and America, there are many reports of the ST398-LA-clone in pigs and in humans who are in contact with pigs. However, various studies in China, including this one, indicate that the ST398 clone could be a CA clone rather than an LA clone. This clone also has been infecting humans for about 2 decades.


Asunto(s)
Variación Genética , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Animales , Técnicas de Tipificación Bacteriana , China , Cromosomas Bacterianos/genética , Microbiología de Alimentos , Staphylococcus aureus Resistente a Meticilina/genética , Pruebas de Sensibilidad Microbiana , Leche/microbiología , Tipificación de Secuencias Multilocus , Porcinos/microbiología
6.
J Affect Disord ; 358: 129-137, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38697224

RESUMEN

BACKGROUND: The underlying pathogenesis of anxiety remain elusive, making the pinpointing of potential therapeutic and diagnostic biomarkers for anxiety paramount to its efficient treatment. METHODS: We undertook a proteome-wide association study (PWAS), fusing human brain proteomes from both discovery (ROS/MAP; N = 376) and validation cohorts (Banner; N = 152) with anxiety genome-wide association study (GWAS) summary statistics. Complementing this, we executed transcriptome-wide association studies (TWAS) leveraging human brain transcriptomic data from the Common Mind Consortium (CMC) to discern the confluence of genetic influences spanning both proteomic and transcriptomic levels. We further scrutinized significant genes through a suite of methodologies. RESULTS: We discerned 14 genes instrumental in the genesis of anxiety through their specific cis-regulated brain protein abundance. Out of these, 6 were corroborated in the confirmatory PWAS, with 4 also showing associations with anxiety via their cis-regulated brain mRNA levels. A heightened confidence level was attributed to 5 genes (RAB27B, CCDC92, BTN2A1, TMEM106B, and DOC2A), taking into account corroborative evidence from both the confirmatory PWAS and TWAS, coupled with insights from mendelian randomization analysis and colocalization evaluations. A majority of the identified genes manifest in brain regions intricately linked to anxiety and predominantly partake in lysosomal metabolic processes. LIMITATIONS: The limited scope of the brain proteome reference datasets, stemming from a relatively modest sample size, potentially curtails our grasp on the entire gamut of genetic effects. CONCLUSION: The genes pinpointed in our research present a promising groundwork for crafting therapeutic interventions and diagnostic tools for anxiety.


Asunto(s)
Ansiedad , Encéfalo , Estudio de Asociación del Genoma Completo , Proteoma , Humanos , Proteoma/genética , Encéfalo/metabolismo , Ansiedad/genética , Ansiedad/metabolismo , Transcriptoma , Proteómica , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/metabolismo
7.
Front Microbiol ; 15: 1381749, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011146

RESUMEN

Introduction: The escalating prevalence of bacterial resistance, particularly multidrug-resistant bacteria like Acinetobacter baumannii, has become a significant global public health concern. The CRISPR-Cas system, a crucial defense mechanism in bacteria against foreign genetic elements, provides a competitive advantage. Type I-Fb and Type I-Fa are two subtypes of CRISPR-Cas systems that were found in A. baumannii, and the I-Fb CRISPR-Cas system regulates antibiotic resistance in A. baumannii. However, it is noteworthy that a majority of clinical isolates of A. baumannii lack or have incomplete CRISPR-Cas systems and most of them are multidrug-resistant. In light of this, our study aimed to examine the impact of antibiotic pressure on the fitness cost of the I-Fb CRISPR-Cas system in A. baumannii. Methods and Results: In the study, we conducted in vitro competition experiments to investigate the influence of sub-minimum inhibitory concentration (sub-MIC) on the CRISPR-Cas systems' fitness cost in A. baumannii. We found that the fitness cost of the CRISPR-Cas system was increased under sub-MIC conditions. The expression of CRISPR-Cas-related genes was decreased, while the conjugation frequency was increased in AB43 under sub-MIC conditions. Through metabolomic analysis, we identified that sub-MIC conditions primarily affected energy metabolism pathways. In particular, we observed increased carbon metabolism, nitrogen metabolism, and intracellular ATP. Notably, the CRISPR-Cas system demonstrated resistance to the efflux pump-mediated resistance. Furthermore, the expression of efflux pump-related genes was increased under sub-MIC conditions. Conclusion: Our findings suggest that the I-Fb CRISPR-Cas system confers a significant competitive advantage in A. baumanni. However, under sub-MIC conditions, its function and the ability to inhibit the energy required for efflux pumps are reduced, resulting in an increased fitness cost and loss of competitive advantage.

8.
iScience ; 27(6): 109942, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38812547

RESUMEN

Biofilm formation plays a significant role in antibiotic resistance, necessitating the search for alternative therapies against biofilm-associated infections. This study demonstrates that 20 µg/mL tryptanthrin can hinder biofilm formation above 50% in various A. baumannii strains. Tryptanthrin impacts various stages of biofilm formation, including the inhibition of surface motility and eDNA release in A. baumannii, as well as an increase in its sensitivity to H202. RT-qPCR analysis reveals that tryptanthrin significantly decreases the expression of the following genes: abaI (19.07%), abaR (33.47%), bfmR (43.41%), csuA/B (64.16%), csuE (50.20%), ompA (67.93%), and katE (72.53%), which are related to biofilm formation and quorum sensing. Furthermore, tryptanthrin is relatively safe and can reduce the virulence of A. baumannii in a Galleria mellonella infection model. Overall, our study demonstrates the potential of tryptanthrin in controlling biofilm formation and virulence of A. baumannii by disrupting different stages of biofilm formation and intercellular signaling communication.

9.
ACS Infect Dis ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949961

RESUMEN

Biofilm formation of Klebsiella pneumoniae can protect bacteria from antibiotics and is difficult to eradicate. Thus, the influence of subinhibitory concentrations of antibiotics on bacteria is becoming increasingly important. Our study showed that subminimum inhibitory concentrations (sub-MICs) of tetracycline antibiotics can increase biofilm formation in minocycline-resistant Klebsiella pneumoniae clinical strains. However, in the bacterial adhesion and invasion experiments, the adhesion and invasion ability decreased and the survival rate of Galleria mellonella increased. Under sub-MICs of tetracycline antibiotics treatment, abnormal stretching of bacteria was observed by scanning electron microscopy. Treatment with sub-MICs of tetracyclines leads to increased surface hydrophobicity and eDNA content and decreased outer membrane permeability. The expression levels of the fimA, luxS, qseB, and qseC genes decreased, the expression level of mrkA increased, and the expression level of acrA was inconsistent under different tetracycline antibiotics treatments. Together, our results suggested that the increase in Klebsiella pneumoniae biofilm formation caused by sub-MICs of tetracycline antibiotics may occur by affecting bacterial physical and chemical properties and associated genes expression.

10.
Mater Horiz ; 10(5): 1705-1718, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-36857679

RESUMEN

Intervertebral disc (IVD) degeneration and herniation often necessitate surgical interventions including a discectomy with or without a nucleotomy, which results in a loss of the normal nucleus pulposus (NP) and a defect in the annulus fibrosus (AF). Due to the limited regenerative capacity of the IVD tissue, the annular tear may remain a persistent defect and result in recurrent herniation post-surgery. Bioadhesives are promising alternatives but show limited adhesion performance, low regenerative capacity, and inability to prevent re-herniation. Here, we report hybrid bioadhesives that combine an injectable glue and a tough sealant to simultaneously repair and regenerate IVD post-nucleotomy. The glue fills the NP cavity while the sealant seals the AF defect. Strong adhesion occurs with the IVD tissues and survives extreme disc loading. Furthermore, the glue can match native NP mechanically, and support the viability and matrix deposition of encapsulated cells, serving as a suitable cell delivery vehicle to promote NP regeneration. Besides, biomechanical tests with bovine IVD motion segments demonstrate the capacity of the hybrid bioadhesives to restore the biomechanics of bovine discs under cyclic loading and to prevent permanent herniation under extreme loading. This work highlights the synergy of bioadhesive and tissue-engineering approaches. Future works are expected to further improve the tissue specificity of bioadhesives and prove their efficacy for tissue repair and regeneration.


Asunto(s)
Anillo Fibroso , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animales , Bovinos , Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/cirugía
11.
Adv Healthc Mater ; 11(11): e2102366, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35122412

RESUMEN

Scars composed of fibrous connective tissues are natural consequences of injury upon incisional wound healing in soft tissues.  Hydrogels that feature a sustained presentation of immunomodulatory cytokines are known to modulate wound healing. However, existing immunomodulatory hydrogels lack interconnected micropores to promote cell ingrowth. Other limitations include invasive delivery procedures and harsh synthesis conditions that are incompatible with drug molecules. Here, hybrid nanocomposite microgels containing interleukin-10 (IL-10) are reported to modulate tissue macrophage phenotype during wound healing. The intercalation of laponite nanoparticles in the polymer network yields microgels with tissue-mimetic elasticity (Young's modulus in the range of 2-6 kPa) and allows the sustained release of IL-10 to promote the differentiation of macrophages toward proregenerative phenotypes. The porous interstitial spaces between microgels promote fibroblast proliferation and fast trafficking (an average speed of ≈14.4 µm h-1 ). The incorporation of hyaluronic acid further enhances macrophage infiltration. The coculture of macrophages and fibroblasts treated with transforming growth factor-beta 1 resulted in a twofold reduction in collagen-I production for microgels releasing IL-10 compared to the IL-10 free group. The new microgels show potential toward regenerative healing by harnessing the antifibrotic behavior of host macrophages.


Asunto(s)
Activación de Macrófagos , Microgeles , Colágeno Tipo I , Fibroblastos , Hidrogeles/farmacología , Interleucina-10
12.
Adv Sci (Weinh) ; 9(2): e2102627, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34811970

RESUMEN

Biological tissues hinge on blood perfusion and mechanical toughness to function. Injectable hydrogels that possess both high permeability and toughness have profound impacts on regenerative medicine but remain a long-standing challenge. To address this issue, injectable, pore-forming double-network hydrogels are fabricated by orchestrating stepwise gelation and phase separation processes. The interconnected pores of the resulting hydrogels enable direct medium perfusion through organ-sized matrices. The hydrogels are amenable to cell encapsulation and delivery while promoting cell proliferation and spreading. They are also pore insensitive, tough, and fatigue resistant. When tested in biomimetic perfusion bioreactors, the hydrogels maintain physical integrity under prolonged, high-frequency biomechanical stimulations (>6000 000 cycles at 120 Hz). The excellent biomechanical performance suggests the great potential of the new injectable hydrogel technology for repairing mechanically dynamic tissues, such as vocal folds, and other applications, such as tissue engineering, biofabrication, organs-on-chips, drug delivery, and disease modeling.


Asunto(s)
Materiales Biocompatibles/química , Biomimética/métodos , Hidrogeles/química , Medicina Regenerativa/métodos , Proliferación Celular , Células Cultivadas , Permeabilidad
13.
Microbiol Spectr ; 10(6): e0278222, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36354319

RESUMEN

The rapid development of methicillin-resistant Staphylococcus aureus (MRSA) drug resistance and the formation of biofilms seriously challenge the clinical application of classic antibiotics. Extracts of the traditional herb Chenopodium ambrosioides L. were found to have strong antibiofilm activity against MRSA, but their mechanism of action remains poorly understood. This study was designed to investigate the antibacterial and antibiofilm activities against MRSA of flavonoids identified from C. ambrosioides L. in combination with classic antibiotics, including ceftazidime, erythromycin, levofloxacin, penicillin G, and vancomycin. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the nonvolatile chemical compositions. Reverse transcription (RT)-PCR was used to investigate potential multitargets of flavonoids based on global transcriptional responses of virulence and antibiotic resistance. A synergistic antibacterial and biofilm-inhibiting activity of the alcoholic extract of the ear of C. ambrosioides L. in combination with penicillin G was observed against MRSA, which proved to be closely related to the interaction of the main components of kaempferol rhamnosides with quercetin. In regard to the mechanism, the increased sensitivity of MRSA to penicillin G was shown to be related to the downregulation of penicillinase with SarA as a potential drug target, while the antibiofilm activity was mainly related to downregulation of various virulence factors involved in the initial and mature stages of biofilm development, with SarA and/or σB as drug targets. This study provides a theoretical basis for further exploration of the medicinal activity of kaempferol rhamnosides and quercetin and their application in combination with penicillin G against MRSA biofilm infection. IMPORTANCE In this study, the synergistic antibacterial and antibiofilm effects of the traditional herb C. ambrosioides L. and the classic antibiotic penicillin G on MRSA provide a potential strategy to deal with the rapid development of MRSA antibiotic resistance. This study also provides a theoretical basis for further optimizing the combined effect of kaempferol rhamnosides, quercetin, and penicillin G and exploring anti-MRSA biofilm infection research with SarA and σB as drug targets.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Quercetina/farmacología , Quempferoles/farmacología , Regulación hacia Abajo , Antibacterianos/farmacología , Flavonoides/farmacología , Biopelículas , Resistencia a las Penicilinas , Pruebas de Sensibilidad Microbiana
14.
Nat Commun ; 13(1): 5035, 2022 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-36028516

RESUMEN

Non-compressible hemorrhage is an unmet clinical challenge that accounts for high mortality in trauma. Rapid pressurized blood flows under hemorrhage impair the function and integrity of hemostatic agents and the adhesion of bioadhesive sealants. Here, we report the design and performance of bioinspired microstructured bioadhesives, formed with a macroporous tough xerogel infused with functional liquids. The xerogel can rapidly absorb interfacial fluids such as whole blood and promote blood clotting, while the infused liquids facilitate interfacial bonding, sealing, and antibacterial function. Their synergy enables the bioadhesives to form tough adhesion on ex vivo human and porcine tissues and diverse engineered surfaces without the need for compression, as well as on-demand instant removal and storage stability. We demonstrate a significantly improved hemostatic efficacy and biocompatibility in rats and pigs compared to non-structured counterparts and commercial products. This work opens new avenues for the development of bioadhesives and hemostatic sealants.


Asunto(s)
Hemostáticos , Adhesivos Tisulares , Animales , Materiales Biocompatibles , Hemorragia , Hemostasis , Humanos , Ratas , Porcinos
15.
Adv Mater ; 33(24): e2007663, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33956371

RESUMEN

Tissue adhesives can form appreciable adhesion with tissues and have found clinical use in a variety of medical settings such as wound closure, surgical sealants, regenerative medicine, and device attachment. The advantages of tissue adhesives include ease of implementation, rapid application, mitigation of tissue damage, and compatibility with minimally invasive procedures. The field of tissue adhesives is rapidly evolving, leading to tissue adhesives with superior mechanical properties and advanced functionality. Such adhesives enable new applications ranging from mobile health to cancer treatment. To provide guidelines for the rational design of tissue adhesives, here, existing strategies for tissue adhesives are synthesized into a multifaceted design, which comprises three design elements: the tissue, the adhesive surface, and the adhesive matrix. The mechanical, chemical, and biological considerations associated with each design element are reviewed. Throughout the report, the limitations of existing tissue adhesives and immediate opportunities for improvement are discussed. The recent progress of tissue adhesives in topical and implantable applications is highlighted, and then future directions toward next-generation tissue adhesives are outlined. The development of tissue adhesives will fuse disciplines and make broad impacts in engineering and medicine.


Asunto(s)
Adhesivos Tisulares , Humanos
16.
Adv Mater ; 33(49): e2104730, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34596923

RESUMEN

Bioprinting, within the emerging field of biofabrication, aims at the fabrication of functional biomimetic constructs. Different 3D bioprinting techniques have been adapted to bioprint cell-laden bioinks. However, single-material bioprinting techniques oftentimes fail to reproduce the complex compositions and diversity of native tissues. Multi-material bioprinting as an emerging approach enables the fabrication of heterogeneous multi-cellular constructs that replicate their host microenvironments better than single-material approaches. Here, bioprinting modalities are reviewed, their being adapted to multi-material bioprinting is discussed, and their advantages and challenges, encompassing both custom-designed and commercially available technologies are analyzed. A perspective of how multi-material bioprinting opens up new opportunities for tissue engineering, tissue model engineering, therapeutics development, and personalized medicine is offered.


Asunto(s)
Bioimpresión , Biomimética , Bioimpresión/métodos , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido
17.
ACS Biomater Sci Eng ; 7(9): 4009-4026, 2021 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-34510905

RESUMEN

Extrusion-based three-dimensional (3D) printing is an emerging technology for the fabrication of complex structures with various biological and biomedical applications. The method is based on the layer-by-layer construction of the product using a printable ink. The material used as the ink should possess proper rheological properties and desirable performances. Composite materials, which are extensively used in 3D printing applications, can improve the printability and offer superior performances for the printed constructs. Herein, we review composite inks with a focus on composite hydrogels. The properties of different additives including fibers and nanoparticles are discussed. The performances of various composite inks in biological and biomedical systems are delineated through analyzing the synergistic effects between the composite ink components. Different applications, including tissue engineering, tissue model engineering, soft robotics, and four-dimensional printing, are selected to demonstrate how 3D-printable composite inks are exploited to achieve various desired functionality. This review finally presents an outlook of future perspectives on the design of composite inks.


Asunto(s)
Tinta , Impresión Tridimensional , Hidrogeles , Reología , Ingeniería de Tejidos
18.
Laryngoscope ; 131(8): 1828-1834, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33068297

RESUMEN

OBJECTIVE: Most acellular injectable biomaterials for vocal fold (VF) wound treatment have limited regenerative potential due to their fast enzymatic degradation and limited recruitment of native cells postinjection. The injection of cells as therapeutic treatment often results in apoptosis due to stresses within the needle and the immune response of the host. Degradable microspheres may improve treatment effectiveness by increasing cell residence time, shielding cells during injection, and offering early protection against the immune system response. The objective of the present study was to investigate the potential of human VF fibroblasts encapsulated in polymeric microspheres as an injectable therapeutic treatment in vitro. METHODS: Alginate, alginate-poly-L-lysine, and alginate-chitosan microspheres were fabricated using electrospraying and characterized in terms of biocompatibility, swelling, and mechanical properties as well as cytokine production. RESULTS: Alginate microspheres were found to have the most desirable properties for VF regeneration. They were resistant to mechanical challenges. They were found to have a stiffness similar to that reported for native VF-lamina propria. They were found to be biocompatible and increased the proliferation of fibroblasts. Human VF fibroblasts encapsulated in alginate microspheres induced the production of interleukin (IL)-8 and IL-4 at 24 hours. CONCLUSION: The alginate microspheres fabricated in this study were found to offer potential advantages, as cell delivery tool. This study highlights the importance of combining biomaterials and cells to expedite the wound-healing process through cytokine production. Future work is aimed to further analysis of the wound-healing properties the microspheres. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1828-1834, 2021.


Asunto(s)
Materiales Biocompatibles/administración & dosificación , Encapsulación Celular/métodos , Fibroblastos/fisiología , Regeneración Tisular Dirigida/métodos , Pliegues Vocales/citología , Alginatos/administración & dosificación , Técnicas de Cultivo de Célula , Proliferación Celular/fisiología , Quitosano/administración & dosificación , Humanos , Inyecciones , Ensayo de Materiales , Microesferas , Membrana Mucosa/citología , Polilisina/administración & dosificación , Polilisina/análogos & derivados , Pliegues Vocales/lesiones , Cicatrización de Heridas/fisiología
19.
ACS Appl Mater Interfaces ; 13(31): 37849-37861, 2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34313124

RESUMEN

Ionotronic hydrogels find wide applications in flexible electronics, wearable/implantable devices, soft robotics, and human-machine interfaces. Their performance and practical translation have been bottlenecked by poor adhesiveness, limited mechanical properties, and the lack of biological functions. The remedies are often associated with complex formulations and sophisticated processing. Here, we report a rational design and facile synthesis of ionotronic tough adhesives (i-TAs), which have excellent mechanical, physical, electrical, and biological properties and promise high scalability and translational potential. They consist of an interpenetrating network with high-density amine groups and highly mobile chains, which enable intrinsic adhesiveness, self-healing, ionic stability, cytocompatibility, and antimicrobial functions. The i-TAs in both pristine and swollen states possess high toughness, stretchability, and strong adhesion to diverse substrates such as tissues and elastomers. The superior mechanical performance is achieved simultaneously with high ionic conductivity and stability in electrolyte solutions. We further demonstrate the use of i-TAs as wearable devices, strain sensors, and sensory sealants. This work is expected to open avenues for new ionotronics with novel functions and stimulate the development and translation of ionotronics.


Asunto(s)
Adhesivos/química , Hidrogeles/química , Resinas Acrílicas/química , Adhesividad , Quitosano/química , Conductividad Eléctrica , Humanos , Ensayo de Materiales , Monitoreo Fisiológico/instrumentación , Movimiento , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Resistencia a la Tracción , Dispositivos Electrónicos Vestibles
20.
Cell Death Dis ; 12(2): 185, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33589592

RESUMEN

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.


Asunto(s)
Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Circular/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Células A549 , Carcinogénesis , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Femenino , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , ARN Circular/biosíntesis , ARN Circular/genética
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