RESUMO
Vocal fold (VF) scarring, a complex problem in laryngology, results from injury and inflammation of the layered architecture of the VFs. The resultant voice hoarseness, for which successful therapeutic options are currently limited, affects the patient's quality of life. A promising strategy to reverse this disorder is the use of antifibrotic drugs. The present study proposes a novel microbead-embedded injectable hydrogel that can sustain the release of the anti-fibrotic drug pirfenidone (PFD) for vocal fold scarring. Microbeads were developed using sodium alginate and gelatin, which were further embedded into a biomimetic and tissue adhesive gellan gum (GG) hydrogel. The microbead-embedded hydrogel exhibited improved injectability, viscoelasticity, tissue adhesiveness, degradability, and swelling compared to the hydrogel without beads. Additionally, the bead-embedded hydrogel could sustain the release of the PFD for a week. In vitro studies showed that the drug-loaded hydrogel could reduce the migration and proliferation of fibroblast cells in a dose-dependent manner. In summary, this study demonstrates the potential of a PFD-loaded injectable hydrogel with enhanced viscoelastic and tissue-adhesive properties for vocal fold scarring applications.
Assuntos
Materiais Biocompatíveis , Cicatriz , Teste de Materiais , Adesivos Teciduais , Prega Vocal , Prega Vocal/patologia , Prega Vocal/efeitos dos fármacos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cicatriz/tratamento farmacológico , Cicatriz/patologia , Humanos , Proliferação de Células/efeitos dos fármacos , Tamanho da Partícula , Microgéis/química , Antifibróticos/química , Antifibróticos/farmacologia , Fibroblastos/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Alginatos/química , Movimento Celular/efeitos dos fármacos , Polissacarídeos Bacterianos , PiridonasRESUMO
Conversion of toxic nitroarenes into less toxic aryl amines, which are the most suitable precursors for different types of compounds, is done with various materials which are costly or take more time for this conversion. In this regards, a silica@poly(chitosan-N-isopropylacrylamide-methacrylic acid) Si@P(CS-NIPAM-MAA) Si@P(CNM) core-shell microgel system was synthesized through free radical precipitation polymerization (FRPP) and then fabricated with palladium nanoparticles (Pd NPs) by in situ-reduction method to form Si@Pd-P(CNM) and characterized with XRD, TEM, FTIR, SEM, and EDX. The catalytic efficiency of Si@Pd-P(CNM) hybrid microgels was studied for reduction of 4-nitroaniline (4NiA) under diverse conditions. Different nitroarenes were successfully transformed into their corresponding aryl amines with high yields using the Si@Pd-P(CNM) system as catalyst and NaBH4 as reductant. The Si@Pd-P(CNM) catalyst exhibited remarkable catalytic efficiency and recyclability as well as maintaining its catalytic effectiveness over multiple cycles.
Assuntos
Acrilamidas , Quitosana , Nanopartículas Metálicas , Paládio , Dióxido de Silício , Paládio/química , Catálise , Dióxido de Silício/química , Quitosana/química , Nanopartículas Metálicas/química , Acrilamidas/química , Microgéis/química , Oxirredução , Metacrilatos/químicaRESUMO
HYPOTHESIS: Engineering plant-based microgel particles (MPs) at a molecular scale is meaningful to prepare functional fat analogues. We hypothesize that oat protein isolate (OPI) and κ-carrageenan (CA) have synergy in MPs formation, using MPs with controllable structure, and further to fabricate fat analogues with adjustable characteristics is feasible. Their digestion fate will also be possibly modulated by interfacial coatings. EXPERIMENTS: OPI-based conjugated MPs with tunable rigidities by changing crosslinking densities were designed. The relationship between microgel structures, and emulsion gel properties was explored through spectroscopy, microstructure, rheology and tribology. The delivery to lycopene, as well as inhibiting digestion behaviors of fat analogues was evaluated in a simulated gastro-intestinal tract. FINDINGS: The rigidity of conjugated MPs could be tailored to optimize the performance of fat analogues. OPI-1 %CA MPs could stabilize emulsions up to 95 % oil fraction with fine texture. Tribological behaviors had a dependence on microgel elasticity and interfacial coatings, medium hard MP-stabilized emulsion was less disrupted without coalescence after oral processing. Digestion was delayed by denser and harder MPs by softening the interfacial particle layer or limiting lipase accessibility. Softer conjugated MPs possessed better flexibility and were broken down more easily leading to a higher rate of lipid digestion.
Assuntos
Avena , Carragenina , Digestão , Microgéis , Tamanho da Partícula , Carragenina/química , Avena/química , Microgéis/química , Proteínas de Plantas/química , Emulsões/química , Propriedades de Superfície , Reologia , Gorduras/química , Gorduras/metabolismoRESUMO
Biomedical applications such as drug delivery, tissue engineering, and functional surface coating rely on switchable adsorption and desorption of specialized guest molecules. Poly(dehydroalanine), a polyzwitterion containing pH-dependent positive and negative charges, shows promise for such reversible loading, especially when integrated into a gel network. Herein, we present the fabrication of poly(dehydroalanine)-derived gels of different size scales and evaluate them with respect to their practical use in biomedicine. Already existing protocols for bulk gelation were remodeled to derive suitable reaction conditions for droplet-based microfluidic synthesis. Depending on the layout of the microfluidic chip, microgels with a size of approximately 30 µm or 200 µm were obtained, whose crosslinking density can be increased by implementing a multi-arm crosslinker. We analyzed the effects of the crosslinker species on composition, permeability, and softness and show that the microgels exhibit advantageous properties inherent to zwitterionic polymer systems, including high hydrophilicity as well as pH- and ionic strength-sensitivity. We demonstrate pH-regulated uptake and release of fluorescent model dyes before testing the adsorption of a small antimicrobial peptide, LL-37. Quantification of the peptide accommodated within the microgels reveals the impact of size and crosslinking density of the microgels. Biocompatibility of the microgels was validated by cell tests.
Assuntos
Microesferas , Concentração de Íons de Hidrogênio , Microgéis/química , Peptídeos/química , Géis/química , Microfluídica , Humanos , Peptídeos Catiônicos Antimicrobianos/químicaRESUMO
BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.
Assuntos
Fibrose , Microbioma Gastrointestinal , Rim , Nanopartículas , Ratos Sprague-Dawley , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Administração Oral , Masculino , Rim/patologia , Rim/efeitos dos fármacos , Nanopartículas/química , Microgéis/química , Lacticaseibacillus casei , Probióticos/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Quitosana/química , Alginatos/química , Triterpenos Pentacíclicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Distribuição Tecidual , Parede CelularRESUMO
Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.
Assuntos
Aminas , Cucumis sativus , Germinação , Ferro , Microgéis , Sementes , Germinação/efeitos dos fármacos , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Cucumis sativus/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/química , Ferro/metabolismo , Ferro/química , Aminas/química , Aminas/metabolismo , Microgéis/química , Compostos de Epóxi/química , Compostos de Epóxi/metabolismo , Peixe-Zebra/metabolismo , AnimaisRESUMO
Granular hydrogels have emerged as a new class of materials for 3D printing, tissue engineering, and food applications due to their extrudability, porosity, and modularity. This work introduces a convenient method to prepare granular hydrogel with tunable properties by modulating the interaction between gum Arabic (GA) and whey protein isolate (WPI) microgels. As the concentration of GA increased, the appearance of the hydrogel changed from fluid liquid to moldable solid, and the microstructure changed from a macro-porous structure with thin walls to a dense structure formed by the accumulation of spherical particles. At a GA concentration of 0.5 %, the hydrogels remained fluid. Granular hydrogels containing 1.0 % GA showed mechanical properties similar to those of tofu (compressive strength: 10.8 ± 0.5 kPa, Young's modulus: 16.7 ± 0.4 kPa), while granular hydrogels containing 1.5 % GA showed mechanical properties similar to those of hawthorn sticks and sausages (compressive strength: 300.4 ± 5.8 kPa; Young's modulus: 200.5 ± 3.4 kPa). The hydrogel with 2.0 % GA was similar to hawthorn sticks, with satisfactory bite resistance and elasticity. Such tunability has led to various application potentials in the food industry to meet consumer demand for healthy, nutritious, and diverse textures.
Assuntos
Goma Arábica , Hidrogéis , Microgéis , Proteínas do Soro do Leite , Goma Arábica/química , Hidrogéis/química , Proteínas do Soro do Leite/química , Microgéis/química , Módulo de Elasticidade , Reologia , Porosidade , Força CompressivaRESUMO
The multifunctionality of advanced laundry detergents primarily relies on the inclusion of functional solid particles, such as pearlescent powder, enzymes, and perfume microcapsules. However, the high-content surfactants in these detergents can render most existing suspending rheology modifiers ineffective, making it challenging to achieve uniform suspension of these functional particles. This compromises the overall functionality of laundry products. To address this, we have developed a binary rheology modifier comprising cellulose microgel and HPMC (hydroxypropyl methylcellulose), acting as the "island" and "chain," respectively. Together, they form an interconnected dynamic network that effectively "encapsulates" the functional particles. Furthermore, the cellulose microgel/HPMC rheology modifier demonstrates versatility, proving effective with various surfactants. Despite its potential, the suspension mechanism of cellulose microgel/HPMC remains elusive. Therefore, we conducted a comprehensive investigation, fabricating cellulose microgels with varying nanofabrication degrees and surface charges through TEMPO oxidation. Our findings highlight the critical role of the surficial structure of T-Microgel, specifically its nanofabrication degree, in influencing the dynamic network's fabrication, thereby impacting yield and thixotropic properties. The surface charge of T-microgel does not significantly influence the process. This research not only elucidates the intricate dynamics of cellulose microgel/HPMC interaction but also provides fundamental insights essential for the development of innovative rheology modifiers tailored for high-content surfactant applications.
Assuntos
Celulose , Microgéis , Reologia , Celulose/química , Microgéis/química , Tensoativos/química , Derivados da Hipromelose/química , Óxidos N-Cíclicos/químicaRESUMO
In the ongoing quest to formulate sensory-rich, low-fat products that maintain structural integrity, this work investigated the potential of bigels, especially those created using innovative Pickering techniques. By harnessing the unique properties of whey protein isolate (WPI) and whey protein microgel (WPM) as interfacial stabilizers, WPM-based Pickering bigels exhibited a remarkable particle localization at the interface due to specific intermolecular interactions. The rise in protein concentration not only intensified particle coverage and interface stabilization but also amplified attributes like storage modulus, yield stress, and adhesiveness, owing to enhanced intermolecular forces and a compact gel matrix. Impressively, WPM-based Pickering bigels outshone in practical applications, showcasing exceptional oil retention during freeze-thaw cycles and extended flavor release-a promising indication for frozen food product applications. Furthermore, these bigels underwent a sensory evolution from a lubricious texture at lower concentrations to a stable plateau at higher ones, offering an enriched consumer experience. In a comparative digestibility assessment, WPM-based Pickering bigels demonstrated superior prowess in decelerating the release of free fatty acids, indicating slowed lipid digestion. This study demonstrates the potential to fine-tune oral sensations and digestive profiles in bigels by modulating Pickering particle concentrations.
Assuntos
Digestão , Microgéis , Paladar , Proteínas do Soro do Leite , Proteínas do Soro do Leite/química , Humanos , Microgéis/química , Manipulação de Alimentos/métodos , Trato Gastrointestinal/metabolismo , SensaçãoRESUMO
Microfluidic cell encapsulation has provided a platform for studying the behavior of individual cells and has become a turning point in single-cell analysis during the last decade. The engineered microenvironment, along with protecting the immune response, has led to increasingly presenting the results of practical and pre-clinical studies with the goals of disease treatment, tissue engineering, intelligent control of stem cell differentiation, and regenerative medicine. However, the significance of cell-substrate interaction versus cell-cell communications in the microgel is still unclear. In this study, monodisperse alginate microgels were generated using a flow-focusing microfluidic device to determine how the cell microenvironment can control human bone marrow-derived mesenchymal stem cells (hBMSCs) viability, proliferation, and biomechanical features in single-cell droplets versus multi-cell droplets. Collected results show insufficient cell proliferation (234 % and 329 %) in both single- and multi-cell alginate microgels. Alginate hydrogels supplemented with poly-l-lysine (PLL) showed a better proliferation rate (514 % and 780 %) in a comparison of free alginate hydrogels. Cell stiffness data illustrate that hBMSCs cultured in alginate hydrogels have higher membrane flexibility and migration potency (Young's modulus equal to 1.06 kPa), whereas PLL introduces more binding sites for cell attachment and causes lower flexibility and migration potency (Young's modulus equal to 1.83 kPa). Considering that cell adhesion is the most important parameter in tissue engineering, in which cells do not run away from a 3D substrate, PLL enhances cell stiffness and guarantees cell attachments. In conclusion, cell attachment to PLL-mediated alginate hydrogels is crucial for cell viability and proliferation. It suggests that cell-cell signaling is good enough for stem cell viability, but cell-PLL attachment alongside cell-cell signaling is crucial for stem cell proliferation and self-renewal.
Assuntos
Alginatos , Adesão Celular , Proliferação de Células , Células-Tronco Mesenquimais , Microgéis , Polilisina , Alginatos/química , Alginatos/farmacologia , Polilisina/química , Polilisina/farmacologia , Humanos , Adesão Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Proliferação de Células/efeitos dos fármacos , Microgéis/química , Microfluídica/métodos , Comunicação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Encapsulamento de Células/métodos , Análise de Célula Única , Autorrenovação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacosRESUMO
Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (â¼940 kJ/m3) and compressive (â¼270 kJ/m3) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care.
Assuntos
Hidrogéis , Adesivos Teciduais , Cicatrização , Hidrogéis/química , Animais , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Cicatrização/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Microgéis/química , Resistência à Tração , Ratos Sprague-DawleyRESUMO
Purpose: The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create nanoparticle-loaded microgels for potential applications in treatment development. Methods: We adopted the process of ionic gelation to generate microgels from sodium alginate and carboxymethyl cellulose. These microgels were loaded with doxorubicin-conjugated amine-functionalized zinc ferrite nanoparticles (AZnFe-NPs). The systems were characterized using various techniques. Toxicity was evaluated in MCF-7 cells. In vitro release studies were conducted at different pH levels at 37 oC, with the drug release kinetics being analyzed using various models. Results: The drug encapsulation efficiency of the created carriers was as high as 70%. The nanoparticle-loaded microgels exhibited pH-responsive behavior and sustained drug release. Drug release from them was mediated via a non-Fickian type of diffusion. Conclusion: Given their high drug encapsulation efficiency, sustained drug release and pH-responsiveness, our nanoparticle-loaded microgels show promise as smart carriers for future treatment applications. Further development and research can significantly benefit the field of drug delivery and treatment development.
Assuntos
Preparações de Ação Retardada , Doxorrubicina , Portadores de Fármacos , Liberação Controlada de Fármacos , Compostos Férricos , Microgéis , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Humanos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Células MCF-7 , Compostos Férricos/química , Concentração de Íons de Hidrogênio , Microgéis/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Alginatos/química , Aminas/química , Carboximetilcelulose Sódica/química , Nanopartículas/química , Zinco/química , Compostos de Zinco/química , Sobrevivência Celular/efeitos dos fármacosRESUMO
Photochemical cross-linking is a key step for manufacturing microgels in numerous applications, including drug delivery, tissue engineering, material production, and wound healing. Existing photochemical cross-linking techniques in microfluidic devices rely on UV curing, which can cause cell and DNA damage. We address this challenge by developing a microfluidic workflow for producing microgels using visible light-driven photochemical cross-linking of aqueous droplets dispersed in a continuous oil phase. We report a proof-of-concept to construct microgels from the protein Bovine Serum Albumin (BSA) with [Ru(bpy)3]2+ mediated cross-linking. By controlling the capillary number of the continuous and dispersed phases, the volumetric flow rate, and the photochemical reaction time within the microfluidic tubing, we demonstrate the construction of protein microgels with controllable and uniform dimensions. Our technique can, in principle, be applied to a wide range of different proteins with biological and responsive properties. This work therefore bridges the gap between hydrogel manufacturing using visible light and microfluidic microgel templating, facilitating numerous biomedical applications.
Assuntos
Reagentes de Ligações Cruzadas , Microgéis , Processos Fotoquímicos , Soroalbumina Bovina , Soroalbumina Bovina/química , Reagentes de Ligações Cruzadas/química , Microgéis/química , Animais , Bovinos , Luz , Dispositivos Lab-On-A-Chip , Técnicas Analíticas MicrofluídicasRESUMO
Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.
Assuntos
Bioimpressão , Carragenina , Carragenina/química , Bioimpressão/métodos , Microgéis/química , Impressão Tridimensional , Engenharia Tecidual/métodos , Hidrogéis/química , Alicerces Teciduais/química , Animais , HumanosRESUMO
Chemically modified oligonucleotides can solve biosensing issues for the development of capture probes, antisense, CRISPR/Cas, and siRNA, by enhancing their duplex-forming ability, their stability against enzymatic degradation, and their specificity for targets with high sequence similarity as microRNA families. However, the use of modified oligonucleotides such as locked nucleic acids (LNA) for biosensors is still limited by hurdles in design and from performances on the material interface. Here we developed a fluorogenic biosensor for non-coding RNAs, represented by polymeric PEG microgels conjugated with molecular beacons (MB) modified with locked nucleic acids (MicroLOCK). By 3D modeling and computational analysis, we designed molecular beacons (MB) inserting spot-on LNAs for high specificity among targets with high sequence similarity (95%). MicroLOCK can reversibly detect microRNA targets in a tiny amount of biological sample (2 µL) at 25 °C with a higher sensitivity (LOD 1.3 fM) without any reverse transcription or amplification. MicroLOCK can hybridize the target with fast kinetic (about 30 min), high duplex stability without interferences from the polymer interface, showing high signal-to-noise ratio (up to S/N = 7.3). MicroLOCK also demonstrated excellent resistance to highly nuclease-rich environments, in real samples. These findings represent a great breakthrough for using the LNA in developing low-cost biosensing approaches and can be applied not only for nucleic acids and protein detection but also for real-time imaging and quantitative assessment of gene targeting both in vitro and in vivo.
Assuntos
Técnicas Biossensoriais , MicroRNAs , Oligonucleotídeos , Técnicas Biossensoriais/métodos , MicroRNAs/análise , MicroRNAs/genética , Oligonucleotídeos/química , Humanos , Microgéis/química , Limite de Detecção , Hibridização de Ácido NucleicoRESUMO
BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.
Assuntos
Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/farmacologia , Humanos , Ácidos Graxos Voláteis/metabolismo , Animais , Limosilactobacillus reuteri/metabolismo , Camundongos , Quitosana/química , Alginatos/química , Alginatos/farmacologia , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Administração Oral , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Receptores Acoplados a Proteínas G/metabolismo , Microgéis/química , Camundongos Endogâmicos BALB C , Ácido Butírico/farmacologia , Ácido Butírico/metabolismoRESUMO
In this study, sodium alginate/ soy protein isolate (SPI) microgels cross-linked by various divalent cations including Cu2+, Ba2+, Ca2+, and Zn2+ were fabricated. Cryo-scanning electron microscopy observations revealed distinctive structural variations among the microgels. In the context of gastric pH conditions, the degree of shrinkage of the microgels followed the sequence of Ca2+ > Ba2+ > Cu2+ > Zn2+. Meanwhile, under intestinal pH conditions, the degree of swelling was ranked as Zn2+ > Ca2+ > Ba2+ > Cu2+. The impact of these variations was investigated through in vitro digestion studies, revealing that all microgels successfully delayed the release of ß-carotene within the stomach. Within the simulated intestinal fluid, the microgel cross-linked with Zn2+ exhibited an initial burst release, while those cross-linked with Cu2+, Ba2+, or Ca2+ displayed a sustained release pattern. This research underscores the potential of sodium alginate/SPI microgels cross-linked with different divalent cations as efficient controlled-release delivery systems.
Assuntos
Alginatos , Preparações de Ação Retardada , Microgéis , Proteínas de Soja , Alginatos/química , Proteínas de Soja/química , Preparações de Ação Retardada/química , Microgéis/química , Concentração de Íons de Hidrogênio , beta Caroteno/química , Cátions Bivalentes/químicaRESUMO
Cardiovascular diseases are a major global cause of morbidity and mortality, and they are often characterized by cardiomyocytes dead that ultimately leads to myocardial ischemia (MI). This condition replaces functional cardiac tissue with fibrotic scar tissue compromising heart function. Injectable systems for the in situ delivery of cells or molecules to assist during tissue repair have emerged as promising approaches for tissue engineering, particularly for myocardial repair. Methacryloyl platelet lysates (PLMA) have been employed for constructing full human-based 3D cell culture matrices and demonstrated potential for xeno-free applications. In this study, we propose using PLMA to produce microparticles (MPs) serving as anchors for cardiac and endothelial cells and ultimately as injectable systems for cardiac tissue repair. The herein reported PLMA MPs were produced by droplet microfluidics and showed great properties for cell attachment. More importantly, it is possible to show the capacity of PLMA MPs to serve as cell microcarriers even in the absence of animal-derived serum supplementation in the culture media.
Assuntos
Materiais Biocompatíveis , Plaquetas , Microgéis , Humanos , Plaquetas/química , Plaquetas/metabolismo , Microgéis/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Células Cultivadas , Técnicas de Cultura de Células , Engenharia Tecidual , Metacrilatos/químicaRESUMO
Microgels are advanced scaffolds for tissue engineering due to their proper biodegradability, good biocompatibility, and high specific surface area for effective oxygen and nutrient transfer. However, most of the current monodispersed microgel fabrication systems rely heavily on various precision pumps, which highly increase the cost and complexity of their downstream application. In this work, we developed a simple and facile system for the controllable generation of uniform alginate microgels by integrating a gas-shearing strategy into a glass microfluidic device. Importantly, the cell-laden microgels can be rapidly prepared in a pump-free manner under an all-aqueous environment. The three-dimensional cultured green fluorescent protein-human A549 cells in alginate microgels exhibited enhanced stemness and drug resistance compared to those under two-dimensional conditions. The pancreatic cancer organoids in alginate microgels exhibited some of the key features of pancreatic cancer. The proposed microgels showed decent monodispersity, biocompatibility, and versatility, providing great opportunities in various biomedical applications such as microcarrier fabricating, organoid engineering, and high-throughput drug screening.
Assuntos
Alginatos , Microgéis , Alginatos/química , Alginatos/farmacologia , Humanos , Microgéis/química , Células A549 , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Dispositivos Lab-On-A-Chip , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
Glycans, composed of linked monosaccharides, play crucial roles in biology and find diverse applications. Enhancing their enzymatic synthesis can be achieved by immobilizing enzymes on materials such as microgels. Here, we present microgels with immobilized glycosyltransferases, synthesized through droplet microfluidics, immobilizing enzymes either via encapsulation or postattachment. SpyTag-SpyCatcher interaction was used for enzyme binding, among others. Fluorescamine and permeability assays confirmed enzyme immobilization and microgel porosity, while enzymatic activities were determined using HPLC. The potential application of microgels in cascade reactions involving multiple enzymes was demonstrated by combining ß4GalT and α3GalT in an enzymatic reaction with high yields. Moreover, a cascade of ß4GalT and ß3GlcNAcT was successfully implemented. These results pave the way toward a modular membrane bioreactor for automated glycan synthesis containing the presented biocatalytic microgels.