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Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.
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Histone deacetylases (HDACs) are key epigenetic regulators and classified into four subtypes. Despite the various roles of each HDAC isoform, the lack of selective HDAC inhibitors has limited the elucidation of their roles in biological systems. HDAC11, the sole class-IV HDAC, is highly expressed in the brain, however, the role of HDAC11 in microglia is not fully understood. Based on the modification of MC1568, we developed a novel HDAC inhibitor, 5. Interestingly, 5 suppresses lipopolysaccharide-induced microglial activation by the initiation of autophagy and subsequent inhibition of nitric oxide production. Furthermore, we demonstrated that 5 significantly alleviates depression-like behavior by inhibiting microglial activation in mouse brain. Our discovery reveals that specific pharmacological regulation of HDAC11 induces autophagy and reactive nitrogen species balance in microglia for the first time, which makes HDAC11 a new therapeutic target for depressive disorder.
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Depresión , Inhibidores de Histona Desacetilasas , Microglía , Animales , Ratones , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Depresión/tratamiento farmacológico , Depresión/genética , Depresión/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismoRESUMEN
Rationale: Mineral particles have been widely used in bone tissue engineering scaffolds due to their osteoconductive and osteoinductive properties. Despite their benefits, mineral particles can induce undesirable inflammation and subsequent bone resorption. Aspirin (Asp) is an inexpensive and widely used anti-inflammatory drug. The goal of this study is to assess the synergistic effect of Asp and optimized mineral particle coating in macroporous scaffolds to accelerate endogenous bone regeneration and reduce bone resorption in a critical-sized bone defect model. Methods: Four commonly used mineral particles with varying composition (hydroxyapatite v.s. tricalcium phosphate) and size (nano v.s. micro) were used. Mineral particles were coated onto gelatin microribbon (µRB) scaffolds. Macrophages (Mφ) were cultured on gelatin µRB scaffolds containing various particles, and Mφ polarization was assessed using PCR and ELISA. The effect of conditioned medium from Mφ on mesenchymal stem cell (MSC) osteogenesis was also evaluated in vitro. Scaffolds containing optimized mineral particles were then combined with varying dosages of Asp to assess the effect in inducing endogenous bone regeneration using a critical-sized cranial bone defect model. In vivo characterization and in vitro cell studies were performed to elucidate the effect of tuning Asp dosage on Mφ polarization, osteoclast (OC) activity, and MSC osteogenesis. Results: Micro-sized tricalcium phosphate (mTCP) particles were identified as optimal in promoting M2 Mφ polarization and rescuing MSC-based bone formation in the presence of conditioned medium from Mφ. When implanted in vivo, incorporating Asp with mTCP-coated µRB scaffolds significantly accelerated endogenous bone formation in a dose-dependent manner. Impressively, mTCP-coated µRB scaffolds containing 20 µg Asp led to almost complete bone healing of a critical-sized cranial bone defect as early as week 2 with no subsequent bone resorption. Asp enhanced M2 Mφ polarization, decreased OC activity, and promoted MSC osteogenesis in a dosage-dependent manner in vivo. These results were further validated using in vitro cell studies. Conclusions: Here, we demonstrate Asp and mineral particle-coated microribbon scaffold provides a promising therapy for repairing critical-sized cranial bone defects via immunomodulation. The leading formulation supports rapid endogenous bone regeneration without the need for exogenous cells or growth factors, making it attractive for translation. Our results also highlight the importance of optimizing mineral particles and Asp dosage to achieve robust bone healing while avoiding bone resorption by targeting Mφ and OCs.
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Resorción Ósea , Gelatina , Humanos , Medios de Cultivo Condicionados , Gelatina/farmacología , Regeneración Ósea , Inmunomodulación , Aspirina/farmacologíaRESUMEN
Recently, miraculous therapy approaches involving adeno-associated virus (AAV) for incurable diseases such as spinal muscular atrophy and inherited retinal dysfunction have been introduced. Nonreplicative, nonpathogenic, low rates of chromosome insertional properties and the existence of neutralizing antibodies are main safety reasons why the FDA approved its use in gene delivery. To date, AAV production always results in a mixture of nontherapeutic (empty) and therapeutic (DNA-loaded) full capsids (10-98%). Such existence of empty viral particles inevitably increases viral doses to human. Thus, the rapid monitoring of empty capsids and reducing the empty-to-full ratio are critical in AAV science. However, transmission electron microscopy (TEM) is the primary tool for distinguishing between empty and full capsids, which creates a research bottleneck because of instrument accessibility and technical difficulty. Herein, we demonstrate that atomic force microscopy (AFM) can be an alternative tool to TEM. The simple, noncontact-mode imaging of AAV particles allows the distinct height difference between full capsids (â¼22 nm) and empty capsids (â¼16 nm). The sphere-to-ellipsoidal morphological distortion observed for empty AAV particles clearly distinguishes them from full AAV particles. Our study indicates that AFM imaging can be an extremely useful, quality-control tool in AAV particle monitoring, which is beneficial for the future development of AAV-based gene therapy.
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Cápside , Dependovirus , Humanos , Dependovirus/genética , Microscopía de Fuerza Atómica , Vectores Genéticos , ADNRESUMEN
Plants release phenolic molecules to protect against invading pathogens. In plant-microorganism relationships, phenolics bind to surface oligosaccharides, inactivating microorganism activities. Inspired by phenol-saccharide interactions in plant defense systems, we designed an adhesive sealant. By screening 16 different saccharides, the O-acetyl group, rich in glucomannan (GM), exhibited rapid, robust binding with the galloyl moiety of a model phenolic molecule, tannic acid (TA). Furthermore, the interaction showed both pH and temperature (upper critical solution temperature) sensitivities. Utilizing O-acetyl-galloyl interactions, materials of all dimensions from beads (0D) to strings (1D), films (2D), and objects (3D) could be prepared, as a suitable platform for printing techniques. GMTA films are elastic, adhesive, water-resistant, and effectively sealed perforations, as demonstrated by (1) a lung incision followed by an air inflation model and (2) a thoracic diaphragm model. STATEMENT OF SIGNIFICANCE: In nature, phenolic molecules are 'nearly always' physically bound with polysaccharides, indicating that the phenolics widen the functions of polysaccharides. An example includes that phenolic-polysaccharide interactions are key defense mechanisms against microbial infection in plants whereas polysaccharide alone functions poorly. Despite the ubiquitous biochemistry of polysaccharide-phenolic interactions, efforts on understanding binding chemistry focusing on phenol/polysaccharide interactions is little. This study is important because we found for the first time that O-acetyl group is the moiety in polysaccharides to which phenolic cis-diol and/or cis-triol is spontaneously bound. The phenol-polysaccharide interaction is non-covalent yet robust, kinetically fast, and reversible. Inspired by the interaction chemistry, a simple mixture of phenolic molecules and O-acetyl group containing polysaccharides such as glucomannan opens a promising fabrication strategy toward functional polysaccharide-based material.
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Fenoles , Polisacáridos , Oligosacáridos , Fenol , TemperaturaRESUMEN
The inevitable bleeding and infections caused by disasters and accidents are the main causes of death owing to extrinsic trauma. Hemostatic agents are often used to quickly suppress bleeding and infection, and they can solve this problem in a short time. Silk fibroin (SF) has poor processibility in water, owing to incomplete solubility therein. In this study, aiming to overcome this disadvantage, a modified silk fibroin (SF-BGE), easily soluble in water, was prepared by introducing butyl glycidyl ether (BGE) into its side chain. Subsequently, a small amount of tannic acid (TA) was introduced to prepare an SF-BGE /TA solution, and ZnO nanoparticles (NPs) were added to the solution to form the coordination bonds between the ZnO and TA, leading to an SF-based nanocomposite hydrogel. A structural characterization of the SF-BGE, SF-BGE/TA, SF-BGE/TA/ZnO, and the coordination bonds between ZnO/TA was observed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the phase change was observed by rheological measurements. The pore formation of the SF-BGE/TA/ZnO hydrogel and dispersibility of ZnO were verified through energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM). The cytocompatible and hemostatic performances of the SF-BGE/TA/ZnO NPs composite hydrogels were evaluated, and the hydrogels showed superior hemostatic and cytocompatible activities. Therefore, the SF-based nanocomposite hydrogel is considered as a promising material for hemostasis.
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Owing to the destruction of ozone layer, the increased exposure to UV on the earth adversely affects not only skin diseases but also wound healing. Although the demand for sunscreens is increasing to protect the human skin from these adverse effects, commercially available sunscreens have some limitations in safety. In this study, silk fibroin (SF) composite with biocompatibility and blood coagulation activity was prepared for a highly safe sunscreen. However, the SF has a disadvantage in that it is difficult to dissolve in water. To improve the solubility of SF, butyl glycidyl ether (BGE) was reacted with the side chain of SF to prepare a freely water-soluble SF (mSF) derivative, and the phase behavior according to the mixing ratio of SF derivative and tannic acid (TA) was observed. In addition, ZnO nanoparticles were added to the mSF-TA solution to form a hydrogel through the coordination bonding. The UV blocking, hemostatic, antibacterial and antioxidant effects of the mSF/TA/ZnO composite hydrogel were evaluated, and the excellent skin compatibility of multifunctional hydrogel sunscreen was confirmed through a skin irritation test.
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Fibroínas , Óxido de Zinc , Fibroínas/química , Humanos , Hidrogeles/química , Seda , Protectores Solares/farmacología , Taninos/química , Agua , Óxido de Zinc/químicaRESUMEN
Although biomaterial-based triboelectric nanogenerators (Bio-TENGs) for use in wearable electronics and implantable sensors have been developed, power generation is not suitable for satisfying the basic requirements for practical applications. Here, to greatly enhance output performances of Bio-TENG devices, an antagonistic approach of diatom frustules (DFs) with amine and fluorine chemical functionalizations is reported. The DFs are treated with piranha solution to increase the density of hydroxyl groups and tribo-positive and tribo-negative composite films are designed with antagonistically functionalized DFs. The tribo-positive composites having electron donating functionality consist of aminated DFs and cellulose nanocrystals (CNCs), while the tribo-negative composite is composed of fluorinated DFs and polydimethylsiloxane (PDMS). An antagonistically and chemically functionalized TENG (ACF TENG) with an efficient contact area of 9.6 cm2 under a force of 8 N and a frequency of 5 Hz exhibits an output voltage of 248 V, a short-circuit current of 16.4 µA, and a power density of 2.01 W m-2 , which is 16.6 times higher than a reference (CNC:PDMS) TENG. This study shows a simple antagonistic approach for chemical functionalization as an efficient method to manipulate the tribo-polarity of bio-additives for enhancing power generation of Bio-TENGs.
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Diatomeas , Dispositivos Electrónicos Vestibles , Suministros de Energía Eléctrica , Electrónica , Nanotecnología/métodosRESUMEN
Stimulator of interferon genes (STING) is an endoplasmic reticulum-membrane protein that plays important roles in cancer immunotherapy by activating innate immune responses. We designed and synthesized STING modulators and characterized compounds 4a and 4c that share a crucial amidobenzimidazole moiety. In vitro STING binding and cell-based activity assays demonstrated the potency and efficacy of the compounds that function as direct STING agonists by stimulating STING downstream signaling and promoting type I interferon immune responses. In vitro metabolic studies and the pharmacokinetic properties of the compounds led us to investigate their anticancer activity in an in vivo syngeneic model. Intravenous injection of compounds 4a and 4c significantly decreased tumor volume in a CT26 murine colorectal carcinoma model, and the immunological memory-derived cancer inhibition was observed in 4c-treated mouse models. The present results suggest the therapeutic potential of the compounds for cancer immunotherapy via STING-mediated immune activation.
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Neoplasias , Receptores de Interferón , Animales , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Interferones , Proteínas de la Membrana/metabolismo , Ratones , Neoplasias/tratamiento farmacológico , Receptores de Interferón/uso terapéuticoRESUMEN
Gelatin is one of the most versatile biopolymers in various biomedical applications. A gelatin derivative gelatin-catechol (Gel-C) was developed in this study to further optimize its chemical and physical properties such as thermal reversibility and injectability. We found that Gel-C remains in a solution state at room temperature, and the temperature-dependent gelation capability of gelatin is well preserved in Gel-C. Its gel-forming temperature decreased to about 10 °C (about 30 °C for gelatin), and a series of gelatin derivatives with different gel-forming temperatures (10-30 °C) were formed by mixing gelatin and Gel-C in different ratios. Additionally, irreversible Gel-C hydrogels could be made without the addition of external stimuli by combining the physical cross-linking of gelatin and the chemical cross-linking of catechol. At the same time, properties of Gel-C hydrogels such as thermal reversibility and injectability could be manipulated by controlling the temperature and pH of the precursor solution. By simulating the formation of an irreversible Gel-C hydrogel in vivo, an in situ gelling system was fabricated by lowering the local temperature of the hydrogel with cold shock, thus realizing targeted and localized molecular delivery with prolonged retention time. This simple system integrated with the temperature responsiveness of gelatin and chemical cross-linking of catechol groups thus provides a promising platform to fabricate an in situ gelling system for drug delivery.
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Catecoles/química , Preparaciones de Acción Retardada/química , Gelatina/química , Hidrogeles/química , Animales , Catecoles/administración & dosificación , Catecoles/síntesis química , Catecoles/toxicidad , Línea Celular , Frío , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/síntesis química , Preparaciones de Acción Retardada/toxicidad , Liberación de Fármacos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Gelatina/administración & dosificación , Gelatina/síntesis química , Gelatina/toxicidad , Hidrogeles/administración & dosificación , Hidrogeles/síntesis química , Hidrogeles/toxicidad , Concentración de Iones de Hidrógeno , Inyecciones Subcutáneas , Masculino , Ratones Desnudos , Transición de Fase/efectos de los fármacos , Albúmina Sérica Bovina/química , Temperatura de TransiciónRESUMEN
The addition of particles during the sol-to-gel conversion process generally enhances the mechanical properties of the resulting hydrogels. However, the impact of the addition of porous particles during such a process remains an open question. Herein, we report hydrogel-to-elastomer conversions by natural porous particles called diatom frustule silica, namely, Melosira nummuloides. The surface pores provide mechanical interlocking points for polymers that are reinforced by gelation. The most critical aspect when choosing polymeric materials is the presence of water-resistant adhesion moieties, such as catechol, along a polymer chain, such as chitosan. Without catechol, no sol-to-gel conversion is observed; thus, no elastomeric hydrogel is produced. The resulting hybrid gel reveals reversible compressibility up to a 60% strain and high stretchability even up to â¼400% in area. Further, in vivo study demonstrates that the hybrid composite gel can be used as a therapeutic for pressure-induced ulcers. The synergy of chemical adhesion and physical chain entanglement via pores provides a way to fabricate a new class of 100% water-based elastomeric materials.
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Diatomeas/química , Elastómeros/química , Hidrogeles/química , Polisacáridos/química , Dióxido de Silicio/química , Quitosano/química , PorosidadRESUMEN
It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H2O2, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. STATEMENT OF SIGNIFICANCE: Recently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.
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Hidrogeles , Adhesivos Tisulares , Adhesivos , Peróxido de Hidrógeno , PielRESUMEN
In cancer immunotherapy, the cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from 'cold' to 'hot' through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity. Furthermore, KAS-08 was validated as an effective STING pathway activator in vitro and in vivo. The synergistic effect of cGAMP-mediated immunity and efficient anti-cancer effects successfully demonstrated the therapeutic potential of KAS-08 for combination therapy in cancer treatment.
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The application of biodegradable and biocompatible materials to triboelectric nanogenerators (TENGs) for harvesting energy from motions of the human body has been attracting significant research interest. Herein, we report diatom bio-silica as a biomaterial additive to enhance the output performance of cellulose nanofibril (CNF)-based TENGs. Diatom frustules (DFs), which are tribopositive bio-silica having hierarchically porous three-dimensional structures and high surface area, have hydrogen bonds with CNFs, resulting in enhanced electron-donating capability and a more roughened surface of the DF-CNF composite film. Hence, DFs were applied to form a tribopositive composite film with CNFs. The DF-CNF biocomposite film is mechanically strong, electron-rich, low-cost, and frictionally rough. The DF-CNF TENG showed an output voltage of 388 V and time-averaged power of 85.5 mW/m2 in the contact-separation mode with an efficient contact area of 4.9 cm2, and the generated power was sufficient for instantaneous illumination of 102 light-emitting diodes. In addition, a cytotoxicity study and biocompatibility tests on rabbit skin suggested that the DF-CNF composite was biologically safe. Moreover, a practical application of the DF-CNF TENG was examined with a self-powered smart mask for human breathing monitoring. This study not only suggests high output performance of biomaterial-based TENGs but also presents the diverse advantages of the DFs in human body-related applications such as self-powered health monitoring masks, skin-attachable power generators, and tactile feedback systems.
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Celulosa/química , Suministros de Energía Eléctrica , Máscaras , Nanofibras/química , Dióxido de Silicio/química , Dispositivos Electrónicos Vestibles , Animales , Pruebas Respiratorias/instrumentación , Celulosa/toxicidad , Diatomeas/química , Eucalyptus/química , Humanos , Masculino , Monitoreo Fisiológico/instrumentación , Nanofibras/toxicidad , Conejos , Dióxido de Silicio/toxicidad , Piel/efectos de los fármacos , Resistencia a la TracciónRESUMEN
Exoskeletons of insects formed by sclerotization processes exhibit superstrong properties in moduli. Here, it is demonstrated that mimicking the sclerotization process using phenol and polyamine molecules unexpectedly results in a 100% ecofriendly, biocompatible waterborne superglue. Oxygen presented in air and dissolved in water acts as an initiator producing phenolic radical/quinone for superglue curing. Despite synthesis-free uses of water, phenol, and polyamine, its adhesion strength is comparable to commercial epoxy glue showing >6 MPa in lap shear strength. The phenol-amine superglue bonds to various substrates including ceramics, woods, fabrics, plastics, metals, and importantly biological tissues. Due to strong adhesion, the superglue effectively seals wounds within a few seconds, and, due to its waterborne nature, no harmful respiratory effect is observed because of any release of volatile organic compounds. The easy, cost-effective preparation of the phenol-amine superglue can revolutionize varieties of industrial, biomedical, daily life processes.
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Adhesivos/química , Materiales Biomiméticos/química , Insectos/metabolismo , Fenol/química , Poliaminas/química , Proteínas/metabolismo , Animales , Benzoquinonas/química , Tecnología Química Verde , Ensayo de Materiales , Fenómenos Mecánicos , Agua/químicaRESUMEN
Given a low concentration of phenols in the naturally occurring aqueous lubricant (mucilage) from hydrated seeds, their biological functions should be severely limited. Here, we introduce an undisclosed natural strategy that enables maximization of phenolic functions through exposing the phenols at the air-seed solid interface. Our findings not only offer a new perspective on plant reproduction physiology but also provide insights into an innovative design of lubricating biomaterials with additional phenolic functions.
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Fenoles/metabolismo , Mucílago de Planta/metabolismo , Semillas/química , Aire , Estructura Molecular , Tamaño de la Partícula , Fenoles/química , Mucílago de Planta/química , Semillas/metabolismo , Propiedades de SuperficieRESUMEN
Special surface wettability attracts significant attention. In this study, dramatic differences in wettability are demonstrated for microparticles with the same chemical composition, SiO2. One is natural silica prepared from the diatom, Melosira nummuloides, and the other is synthetic silica. We found that surface properties of synthetic silica are hydro- and hemophobic. However, diatom frustule silica exhibits superhydrophilicity and even superhemophilicity. Interestingly, such superhydrophilicity of natural silica is not solely originated from nanoporous structures of diatoms but from the synergy of high-density silanol anions and the nanoarchitecture. Furthermore, the observation of superhemophilicity of natural silica is also an interesting finding, because not all superhydrophilic surfaces show superhemophilicity. We demonstrate that superhemowettability is a fundamental principle for developing micropowder-based hemostatic materials despite existing hemorrhaging studies using diatoms.
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Diatomeas , Hemostáticos , Nanoestructuras , Dióxido de Silicio , Propiedades de SuperficieRESUMEN
Enzymatic cross-linking of polymer-catechol conjugates in the presence of horseradish peroxidase (HRP) and H2O2 has emerged as an important method to fabricate in situ-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, because of the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of the polymer with optimized tissue adhesive property is still challenging. In this study, a poly(γ-glutamic acid) (γ-PGA)-dopamine (PGADA) conjugate was synthesized, and in situ hydrogels were fabricated via enzymatic cross-linking of a catechol moiety. To optimize the tissue adhesive property of the PGADA hydrogel, the effect of various factors, such as polymer concentration, catechol substitution degree (DS), HRP concentration, and H2O2 content, on the gelation behavior and mechanical strength was investigated. The gelation behavior of PGADA hydrogels was characterized using a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength in vitro and ex vivo.
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Hidrogeles , Adhesivos Tisulares , Ácido Glutámico , Peróxido de Hidrógeno , Ácido Poliglutámico/análogos & derivadosRESUMEN
Chitosan-catechol, inspired from mussel-adhesive-proteins, is characterized by the formation of an adhesive membrane complex through instant bonding with serum proteins not found in chitosan. Using this intrinsic property, chitosan-catechol is widely applied for hemostatic needles, general hemostatic materials, nanoparticle composites, and 3D printing. Despite its versatility, the practical use of chitosan-catechol in the clinic is limited due to its undesired immune responses. Herein, a catechol-conjugated glycol chitosan is proposed as an alternative hemostatic hydrogel with negligible immune responses enabling the replacement of chitosan-catechol. Comparative cellular toxicity and in vivo skin irritation between chitosan-catechol and glycol chitosan-catechol are evaluated. Their immune responses are also assessed using histological analysis after subcutaneous implantation into mice. The results show that glycol chitosan-catechol significantly attenuates the immune response compared with chitosan-catechol; this finding is likely due to the antibiofouling effect of ethylene glycol groups and the reduced adhesion of immune cells. Finally, the tissue adhesion and hemostatic ability of glycol chitosan-catechol hydrogels reveal that these ethylene glycol groups do not dramatically modify the adhesiveness and hemostatic ability compared with nonglycol chitosan-catechol. This study suggests that glycol chitosan-catechol can be a promising alternative to chitosan-catechol in various biomedical fields such as hemostatic agents.