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1.
Nat Commun ; 11(1): 4757, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958771

RESUMO

Local tissue mechanics play a critical role in cell function, but measuring these properties at cellular length scales in living 3D tissues can present considerable challenges. Here we present thermoresponsive, smart material microgels that can be dispersed or injected into tissues and optically assayed to measure residual tissue elasticity after creep over several weeks. We first develop and characterize the sensors, and demonstrate that internal mechanical profiles of live multicellular spheroids can be mapped at high resolutions to reveal broad ranges of rigidity within the tissues, which vary with subtle differences in spheroid aggregation method. We then show that small sites of unexpectedly high rigidity develop in invasive breast cancer spheroids, and in an in vivo mouse model of breast cancer progression. These focal sites of increased intratumoral rigidity suggest new possibilities for how early mechanical cues that drive cancer cells towards invasion might arise within the evolving tumor microenvironment.


Assuntos
Fenômenos Biomecânicos , Técnicas Biossensoriais/métodos , Hidrogéis/química , Animais , Técnicas Biossensoriais/instrumentação , Linhagem Celular , Elasticidade , Humanos , Camundongos , Modelos Biológicos , Neoplasias Experimentais/patologia , Esferoides Celulares/patologia , Esferoides Celulares/fisiologia , Temperatura
2.
Nat Commun ; 11(1): 4692, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943624

RESUMO

Hemicelluloses, a family of heterogeneous polysaccharides with complex molecular structures, constitute a fundamental component of lignocellulosic biomass. However, the contribution of each hemicellulose type to the mechanical properties of secondary plant cell walls remains elusive. Here we homogeneously incorporate different combinations of extracted and purified hemicelluloses (xylans and glucomannans) from softwood and hardwood species into self-assembled networks during cellulose biosynthesis in a bacterial model, without altering the morphology and the crystallinity of the cellulose bundles. These composite hydrogels can be therefore envisioned as models of secondary plant cell walls prior to lignification. The incorporated hemicelluloses exhibit both a rigid phase having close interactions with cellulose, together with a flexible phase contributing to the multiscale architecture of the bacterial cellulose hydrogels. The wood hemicelluloses exhibit distinct biomechanical contributions, with glucomannans increasing the elastic modulus in compression, and xylans contributing to a dramatic increase of the elongation at break under tension. These diverging effects cannot be explained solely from the nature of their direct interactions with cellulose, but can be related to the distinct molecular structure of wood xylans and mannans, the multiphase architecture of the hydrogels and the aggregative effects amongst hemicellulose-coated fibrils. Our study contributes to understanding the specific roles of wood xylans and glucomannans in the biomechanical integrity of secondary cell walls in tension and compression and has significance for the development of lignocellulosic materials with controlled assembly and tailored mechanical properties.


Assuntos
Parede Celular/química , Celulose/química , Extratos Vegetais/química , Plantas/química , Polissacarídeos/química , Madeira/química , Configuração de Carboidratos , Sequência de Carboidratos , Catárticos/química , Citoesqueleto/química , Hidrogéis/química , Mananas , Xilanos/química
3.
Nat Commun ; 11(1): 4502, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908136

RESUMO

Biological tissues, such as muscle, can increase their mechanical strength after swelling due to the existence of many biological membrane barriers that can regulate the transmembrane transport of water molecules and ions. Oppositely, typical synthetic materials show a swelling-weakening behavior, which always suffers from a sharp decline in mechanical strength after swelling, because of the dilution of the network. Here, we describe a swelling-strengthening phenomenon of polymer materials achieved by a bioinspired strategy. Liposomal membrane nanobarriers are covalently embedded in a crosslinked network to regulate transmembrane transport. After swelling, the stretched network deforms the liposomes and subsequently initiates the transmembrane diffusion of the encapsulated molecules that can trigger the formation of a new network from the preloaded precursor. Thanks to the tough nature of the double-network structure, the swelling-strengthening phenomenon is achieved to polymer hydrogels successfully. Swelling-triggered self-strengthening enables the development of various dynamic materials.


Assuntos
Materiais Biomiméticos/química , Hidrogéis/química , Lipossomos/química , Nanoestruturas/química , Força Compressiva , Reagentes para Ligações Cruzadas/química , Lipossomos/ultraestrutura , Teste de Materiais , Microscopia Eletrônica de Transmissão , Nanoestruturas/ultraestrutura , Resistência à Tração
4.
Nat Commun ; 11(1): 4536, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913189

RESUMO

Natural musculoskeletal systems have been widely recognized as an advanced robotic model for designing robust yet flexible microbots. However, the development of artificial musculoskeletal systems at micro-nanoscale currently remains a big challenge, since it requires precise assembly of two or more materials of distinct properties into complex 3D micro/nanostructures. In this study, we report femtosecond laser programmed artificial musculoskeletal systems for prototyping 3D microbots, using relatively stiff SU-8 as the skeleton and pH-responsive protein (bovine serum albumin, BSA) as the smart muscle. To realize the programmable integration of the two materials into a 3D configuration, a successive on-chip two-photon polymerization (TPP) strategy that enables structuring two photosensitive materials sequentially within a predesigned configuration was proposed. As a proof-of-concept, we demonstrate a pH-responsive spider microbot and a 3D smart micro-gripper that enables controllable grabbing and releasing. Our strategy provides a universal protocol for directly printing 3D microbots composed of multiple materials.


Assuntos
Biomimética/métodos , Compostos de Epóxi/efeitos da radiação , Fenômenos Fisiológicos Musculoesqueléticos , Polímeros/efeitos da radiação , Robótica/métodos , Soroalbumina Bovina/efeitos da radiação , Biomimética/instrumentação , Compostos de Epóxi/química , Hidrogéis/química , Hidrogéis/efeitos da radiação , Concentração de Íons de Hidrogênio , Lasers , Polimerização/efeitos da radiação , Polímeros/química , Impressão Tridimensional , Robótica/instrumentação , Soroalbumina Bovina/química
5.
Nat Commun ; 11(1): 4193, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826921

RESUMO

Photochemical reactions are a powerful tool in (bio)materials design due to the spatial and temporal control light can provide. To extend their applications in biological setting, the use of low-energy, long wavelength light with high penetration propertiesis required. Further regulation of the photochemical process by additional stimuli, such as pH, will open the door for construction of highly regulated systems in nanotechnology- and biology-driven applications. Here we report the green light induced [2+2] cycloaddition of a halochromic system based on a styrylquinoxaline moiety, which allows for its photo-reactivity to be switched on and off by adjusting the pH of the system. Critically, the [2+2] photocycloaddition can be activated by green light (λ up to 550 nm), which is the longest wavelength employed to date in catalyst-free photocycloadditions in solution. Importantly, the pH-dependence of the photo-reactivity was mapped by constant photon action plots. The action plots further indicate that the choice of solvent strongly impacts the system's photo-reactivity. Indeed, higher conversion and longer activation wavelengths were observed in water compared to acetonitrile under identical reaction conditions. The wider applicability of the system was demonstrated in the crosslinking of an 8-arm PEG to form hydrogels (ca. 1 cm in thickness) with a range of mechanical properties and pH responsiveness, highlighting the potential of the system in materials science.


Assuntos
Reação de Cicloadição/métodos , Hidrogéis/química , Luz , Processos Fotoquímicos , Animais , Catálise , Sobrevivência Celular , Fibroblastos , Concentração de Íons de Hidrogênio , Camundongos , Fótons , Polímeros/química , Reologia
6.
PLoS One ; 15(8): e0237479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790806

RESUMO

OBJECTIVE: As native cartilage consists of different phenotypical zones, this study aims to fabricate different types of neocartilage constructs from collagen hydrogels and human mesenchymal stromal cells (MSCs) genetically modified to express different chondrogenic factors. DESIGN: Human MSCs derived from bone-marrow of osteoarthritis (OA) hips were genetically modified using adenoviral vectors encoding sex-determining region Y-type high-mobility-group-box (SOX) 9, transforming growth factor beta (TGFB) 1 or bone morphogenetic protein (BMP) 2 cDNA, placed in type I collagen hydrogels and maintained in serum-free chondrogenic media for three weeks. Control constructs contained unmodified MSCs or MSCs expressing GFP. The respective constructs were analyzed histologically, immunohistochemically, biochemically, and by qRT-PCR for chondrogenesis and hypertrophy. RESULTS: Chondrogenesis in MSCs was consistently and strongly induced in collagen I hydrogels by the transgenes SOX9, TGFB1 and BMP2 as evidenced by positive staining for proteoglycans, chondroitin-4-sulfate (CS4) and collagen (COL) type II, increased levels of glycosaminoglycan (GAG) synthesis, and expression of mRNAs associated with chondrogenesis. The control groups were entirely non-chondrogenic. The levels of hypertrophy, as judged by expression of alkaline phosphatase (ALP) and COL X on both the protein and mRNA levels revealed different stages of hypertrophy within the chondrogenic groups (BMP2>TGFB1>SOX9). CONCLUSIONS: Different types of neocartilage with varying levels of hypertrophy could be generated from human MSCs in collagen hydrogels by transfer of genes encoding the chondrogenic factors SOX9, TGFB1 and BMP2. This technology may be harnessed for regeneration of specific zones of native cartilage upon damage.


Assuntos
Proteína Morfogenética Óssea 2/genética , Hidrogéis/química , Fatores de Transcrição SOX9/genética , Fator de Crescimento Transformador beta1/genética , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Cartilagem/citologia , Cartilagem/metabolismo , Cartilagem/patologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrogênese/genética , Colágeno Tipo I/química , Colágeno Tipo X/genética , Meios de Cultura Livres de Soro/química , Glicosaminoglicanos/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , RNA Mensageiro/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
7.
Int J Nanomedicine ; 15: 4959-4967, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764929

RESUMO

Background: Particle-based drug delivery systems (DDSs) have a demonstrated value for drug discovery and development. However, some problems remain to be solved, such as limited stimuli, visual-monitoring. Aim: To develop an intelligent multicolor DDSs with both near-infrared (NIR) controlled release and macroscopic color changes. Materials and Methods: Microparticles comprising GO/pNIPAM/PEGDA composite hydrogel inverse opal scaffolds, with dextran and calcium alginate hydrogel were synthesized using SCCBs as the template. The morphology of microparticle was observed under scanning electron microscopy, and FITC-dextran-derived green fluorescence images were determined using a confocal laser scanning microscope. During the drug release, FITC-dextran-derived green fluorescence images were captured using fluorescent inverted microscope. The relationship between the power of NIR and the drug release rate was obtained using the change in optical density (OD) values. Finally, the amount of drug released could be estimated quantitatively used the structural color or the reflection peak position. Results: A fixed concentration 8% (v/v) of PEGDA and 4mg/mL of GO was chosen as the optimal concentration based on the balance between appropriate volume shrinkage and structure color. The FITC-dextran was uniformly encapsulated in the particles by using 0.2 wt% sodium alginate. The microcarriers shrank because of the photothermal response and the intrinsic fluorescence intensity of FITC-dextran in the microparticles gradually decreased at the same time, indicating drug release. With an increasing duration of NIR irradiation, the microparticles gradually shrank, the reflection peak shifted toward blue and the structural color changed from red to orange, yellow, green, cyan, and blue successively. The drug release quantity can be predicted by the structural color of microparticles. Conclusion: The multicolor microparticles have great potential in drug delivery systems because of its vivid reporting color, excellent photothermal effect, and the good stimuli responsivity.


Assuntos
Portadores de Fármacos/química , Microesferas , Resinas Acrílicas/química , Alginatos/química , Cor , Dextranos/química , Liberação Controlada de Fármacos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Hidrogéis/química , Fenômenos Ópticos , Polietilenoglicóis/química
8.
Int J Nanomedicine ; 15: 5097-5111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764939

RESUMO

Introduction: In this in-vitro study, we designed a 3D printed composite of zinc oxide (ZnO) nanoparticles (NPs) with photocatalytic activities encapsulated within hydrogel (alginate) constructs, for antibacterial purposes applicable towards wound healing. We primarily sought to confirm the mechanical properties and cell compatibility of these ZnO NP infused scaffolds. Methods: The antibacterial property of the ZnO NPs was confirmed by hydroxyl radical generation using ultraviolet (U.V.) photocatalysis. Titanium dioxide (TiO2), a well-known antibacterial compound, was used as a positive control (1% w/v) for the ZnO NP-based alginate constructs and their antibacterial efficacies compared. Among the ZnO group, 3D printed gels containing 0.5% and 1% w/v of ZnO were analyzed and compared with manually casted samples via SEM, swelling evaluation, and rheological analysis. Envisioning an in-vivo application for the 3D printed ZnO NP-based alginates, we studied their antibacterial properties by bacterial broth testing, cytocompatibility via live/dead assay, and moisture retention capabilities utilizing a humidity sensor. Results: 3D printed constructs revealed significantly greater pore sizes and enhanced structural stability compared to manually casted samples. For all samples, the addition of ZnO or TiO2 resulted in significantly stiffer gels in comparison with the alginate control. Bacterial resistance testing on Staphylococcus epidermidis indicated the addition of ZnO NPs to the gels decreased bacterial growth when compared to the alginate only gels. Cell viability of STO-fibroblasts was not adversely affected by the addition of ZnO NPs to the alginate gels. Furthermore, the addition of increasing doses of ZnO NPs to the alginate demonstrated increased humidity retention in gels. Discussion: The customization of 3D printed alginates containing antibacterial ZnO NPs leads to an alternative that allows accessible mobility of molecular exchange required for improving chronic wound healing. This scaffold can provide a cost-effective and durable antibacterial treatment option.


Assuntos
Alginatos/química , Alginatos/farmacologia , Hidrogéis/química , Nanopartículas/química , Cicatrização/efeitos dos fármacos , Óxido de Zinco/química , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia
9.
Ecotoxicol Environ Saf ; 202: 110924, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800211

RESUMO

Fabrication of poly-(N-isopropylmethacrylamide-co-methacrylic acid) [p(NMA)] microgels to be utilized as microreactors to synthesize stable Ag nanoparticles for catalytic reductive degradation of dyes has been addressed in this work. Both p(NMA) microgel and Ag-p(NMA) hybrid microgel systems have been analyzed by Fourier transform infra-red and Dynamic light scattering, Ultraviolet-Visible spectroscopy, X-ray diffraction and Transmission electron microscopy. Catalytic activity of Ag-p(NMA) towards reductive degradation of Congo Red (CR), Methyl Orange (MO) and Alizarin Yellow (AY) was investigated under different operating conditions. Spectrophotometry was employed to check the progress of reaction while the rate constant (kapp) value of degradation reaction was determined under various conditions to optimize reaction parameters for rapid and economical degradation of these dyes. An increase in kapp value was observed by increasing feed content of dye up to a certain value that decreases again by further increment in dye concentration which reflects that catalysis follows Langmuir-Hinshelwood mechanism. A gradual increase in the kapp value was also observed with increasing quantity of hybrid microgel used as a catalyst. By comparing kapp values of degradation of aforementioned dyes, it was found that Ag-p(NMA) hybrid microgel gives better activity for MO dye degradation in comparison to catalytic degradation of CR and AY.


Assuntos
Compostos Azo/química , Nanopartículas Metálicas/química , Prata/química , Catálise , Corantes/química , Vermelho Congo/química , Hidrogéis/química , Microscopia Eletrônica de Transmissão , Polímeros/química , Espectrofotometria , Difração de Raios X
10.
Ecotoxicol Environ Saf ; 202: 110935, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800218

RESUMO

This study investigated the ability of dual crosslinked interpenetrating polymer network (IPN) blend beads (DIN:SA/PVA-beads), composed of sodium alginate (SA) and poly (vinyl alcohol) (PVA), as a base-triggered carrier for the controlled release of dinotefuran (DIN) in Spodoptera litera midgut. The blend beads were characterized for morphology, encapsulation efficiency, swelling degree, and in vitro release of the blend beads were characterized. The results revealed that the double-crosslinked gel beads had a tightly interpenetrating network structure and exhibited a satisfactory embedding effect for DIN. The maximum of the DIN loading capacity was approximately 1.01%, with a high encapsulation efficiency of 83.19%. The triggered release of DIN from the blend beads was studied in deionized water (pH 3.0-11.0) via high-performance liquid chromatography (HPLC); it was found that the release rate was higher in alkaline pH conditions than in acidic and neutral conditions. An in vivo dynamics and degradation study also demonstrated that the excellent release characteristics of DIN:SA/PVA-beads in the midgut of S. litera. This study provides a promising controlled-release form of dinotefuran that is more effective and can be used for the targeted control of pests with alkaline midgut.


Assuntos
Guanidinas/metabolismo , Neonicotinoides/metabolismo , Nitrocompostos/metabolismo , Spodoptera/metabolismo , Alginatos/química , Animais , Preparações de Ação Retardada/química , Etanol , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Polímeros , Álcool de Polivinil/química
11.
Nat Commun ; 11(1): 4090, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796831

RESUMO

hnRNPA2 is a human ribonucleoprotein (RNP) involved in RNA metabolism. It forms fibrils both under cellular stress and in mutated form in neurodegenerative conditions. Previous work established that the C-terminal low-complexity domain (LCD) of hnRNPA2 fibrillizes under stress, and missense mutations in this domain are found in the disease multisystem proteinopathy (MSP). However, little is known at the atomic level about the hnRNPA2 LCD structure that is involved in those processes and how disease mutations cause structural change. Here we present the cryo-electron microscopy (cryoEM) structure of the hnRNPA2 LCD fibril core and demonstrate its capability to form a reversible hydrogel in vitro containing amyloid-like fibrils. Whereas these fibrils, like pathogenic amyloid, are formed from protein chains stacked into ß-sheets by backbone hydrogen bonds, they display distinct structural differences: the chains are kinked, enabling non-covalent cross-linking of fibrils and disfavoring formation of pathogenic steric zippers. Both reversibility and energetic calculations suggest these fibrils are less stable than pathogenic amyloid. Moreover, the crystal structure of the disease-mutation-containing segment (D290V) of hnRNPA2 suggests that the replacement fundamentally alters the fibril structure to a more stable energetic state. These findings illuminate how molecular interactions promote protein fibril networks and how mutation can transform fibril structure from functional to a pathogenic form.


Assuntos
Amiloide/química , Amiloide/metabolismo , Microscopia Crioeletrônica/métodos , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/ultraestrutura , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/ultraestrutura , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/química , Humanos , Hidrogéis/química , Proteínas de Ligação a RNA/química
12.
Int J Nanomedicine ; 15: 4739-4752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753862

RESUMO

Purpose: Combined chemotherapeutic drug and protein drug has been a widely employed strategy for tumor treatment. To realize both tumor accumulation and deep tumor penetration for drugs with different pharmacokinetics, we propose a structure-transformable, thermo-pH dual responsive co-delivery system to co-load granzyme B/docetaxel (GrB/DTX). Methods: Thermo-sensitive hydrogels based on diblock copolymers (mPEG-b-PELG) were synthesized through ring opening polymerization. GrB/DTX mini micelles (GDM) was developed by co-loading these two drugs in pH-sensitive mini micelles, and the GDM-incorporated thermo-sensitive hydrogel (GDMH) was constructed. The thermo-induced gelation behavior of diblock copolymers and the physiochemical properties of GDMH were characterized. GDMH degradation and deep tumor penetration of released mini micelles were confirmed. The pH-sensitive disassembly and lysosomal escape abilities of released mini micelles were evaluated. In vitro cytotoxicity was studied using MTT assays and the in vivo antitumor efficacy study was evaluated in B16-bearing C57BL/6 mice. Results: GDMH was gelatinized at body temperature and can be degraded by proteinase to release mini micelles. The mini micelles incorporated in GDMH can achieve deep tumor penetration and escape from lysosomes to release GrB and DTX. MTT results showed that maximum synergistic antitumor efficacy of GrB and DTX was observed at mass ratio of 1:100. Our in vivo antitumor efficacy study showed that GDMH inhibited tumor growth in the subcutaneous tumor model and in the post-surgical recurrence model. Conclusion: The smart-designed transformable GDMH can facilitate tumor accumulation, deep tumor penetration, and rapid drug release to achieve synergistic chemo-protein therapy.


Assuntos
Antineoplásicos/uso terapêutico , Hidrogéis/química , Neoplasias/tratamento farmacológico , Temperatura , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Docetaxel/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Feminino , Granzimas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Injeções , Camundongos Endogâmicos C57BL , Micelas , Neoplasias/patologia , Polietilenoglicóis/química
13.
Nat Commun ; 11(1): 3859, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737298

RESUMO

Non-enzymatic proteins including antibodies function as biomarkers and are used as biopharmaceuticals in several diseases. Protein-responsive soft materials capable of the controlled release of drugs and proteins have potential for use in next-generation diagnosis and therapies. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system is developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging shows that the supramolecular/agarose hydrogel composite consists of orthogonal domains of supramolecular fibers and agarose, which play distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allows for controlled release of the embedded RNase in response to an antibody. Such composite hydrogels would be promising as a matrix embedded in a body, which can autonomously release biopharmaceuticals by sensing biomarker proteins.


Assuntos
Anidrase Carbônica II/química , Preparações de Ação Retardada/síntese química , Hidrogéis/química , Ribonucleases/química , Sefarose/química , Animais , Anticorpos/química , Avidina/química , Biotina/química , Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/química , Bovinos , Ativação Enzimática , Transição de Fase , Reologia , Ribonucleases/antagonistas & inibidores , Sulfonamidas/química
14.
Nat Commun ; 11(1): 3850, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737322

RESUMO

Resolving the distribution of specific proteins at the nanoscale in the ultrastructural context of the cell is a major challenge in fluorescence microscopy. We report the discovery of a new principle for an optical contrast equivalent to electron microscopy (EM) which reveals the ultrastructural context of the cells with a conventional confocal microscope. By decrowding the intracellular space through 13 to 21-fold physical expansion while simultaneously retaining the proteins, bulk (pan) labeling of the proteome resolves local protein densities and reveals the cellular nanoarchitecture by standard light microscopy.


Assuntos
Imageamento Tridimensional/métodos , Microscopia de Fluorescência/métodos , Proteoma/análise , Coloração e Rotulagem/métodos , Acrilamidas/química , Reagentes para Ligações Cruzadas/química , Corantes Fluorescentes/química , Células HeLa , Humanos , Hidrogéis/química , Espaço Intracelular/química , Succinimidas/química , Inclusão do Tecido/métodos
15.
Nat Commun ; 11(1): 4032, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788575

RESUMO

Hydrogel-based devices are widely used as flexible electronics, biosensors, soft robots, and intelligent human-machine interfaces. In these applications, high stretchability, low hysteresis, and anti-fatigue fracture are essential but can be rarely met in the same hydrogels simultaneously. Here, we demonstrate a hydrogel design using tandem-repeat proteins as the cross-linkers and random coiled polymers as the percolating network. Such a design allows the polyprotein cross-linkers only to experience considerable forces at the fracture zone and unfold to prevent crack propagation. Thus, we are able to decouple the hysteresis-toughness correlation and create hydrogels of high stretchability (~1100%), low hysteresis (< 5%), and high fracture toughness (~900 J m-2). Moreover, the hydrogels show a high fatigue threshold of ~126 J m-2 and can undergo 5000 load-unload cycles up to 500% strain without noticeable mechanical changes. Our study provides a general route to decouple network elasticity and local mechanical response in synthetic hydrogels.


Assuntos
Reagentes para Ligações Cruzadas/química , Hidrogéis/química , Poliproteínas/química , Estresse Mecânico , Resinas Acrílicas/química , Fluorescência , Fenômenos Mecânicos
16.
PLoS One ; 15(7): e0219632, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706829

RESUMO

INTRODUCTION: Surgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy. METHODS: The development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells. RESULTS: The DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment. CONCLUSIONS: These findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Hidrogéis/química , Paclitaxel/uso terapêutico , Peptídeos/química , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Sistema Nervoso Central/patologia , Portadores de Fármacos/química , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Paclitaxel/química , Taxa de Sobrevida , Temozolomida/química , Temozolomida/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
17.
PLoS One ; 15(7): e0236371, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706802

RESUMO

We present a simple but accurate algorithm to calculate the flow and shear rate profile of shear thinning fluids, as typically used in biofabrication applications, with an arbitrary viscosity-shear rate relationship in a cylindrical nozzle. By interpolating the viscosity with a set of power-law functions, we obtain a mathematically exact piecewise solution to the incompressible Navier-Stokes equation. The algorithm is validated with known solutions for a simplified Carreau-Yasuda fluid, full numerical simulations for a realistic chitosan hydrogel as well as experimental velocity profiles of alginate and chitosan solutions in a microfluidic channel. We implement the algorithm in an easy-to-use Python tool, included as Supplementary Material, to calculate the velocity and shear rate profile during the printing process, depending on the shear thinning behavior of the bioink and printing parameters such as pressure and nozzle size. We confirm that the shear stress varies in an exactly linear fashion, starting from zero at the nozzle center to the maximum shear stress at the wall, independent of the shear thinning properties of the bioink. Finally, we demonstrate how our method can be inverted to obtain rheological bioink parameters in-situ directly before or even during printing from experimentally measured flow rate versus pressure data.


Assuntos
Alginatos/química , Quitosana/química , Hidrogéis/química , Agulhas , Impressão Tridimensional/instrumentação , Algoritmos , Hidrodinâmica , Microfluídica , Resistência ao Cisalhamento , Viscosidade
18.
Proc Natl Acad Sci U S A ; 117(31): 18310-18316, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32675247

RESUMO

Bionic electronic skin (E-skin) that could convert external physical or mechanical stimuli into output signals has a wide range of applications including wearable devices, artificial prostheses, software robots, etc. Here, we present a chameleon-inspired multifunctional E-skin based on hydroxypropyl cellulose (HPC), Poly(Acrylamide-co-Acrylic acid) (PACA), and carbon nanotubes (CNTs) composited liquid-crystal hydrogel. We found that the HPC could still form cholesteric liquid-crystal photonic structures with the CNTs additive for enhancing their color saturation and PACA polymerization for locating their assembled periodic structures. As the composite hydrogel containing HPC elements and the PACA scaffold responds to different stimuli, such as temperature variations, mechanical pressure, and tension, it could correspondingly change its volume or internal nanostructure and report these as visible color switches. In addition, due to the additive of CNTs, the composite hydrogel could also output these stimuli as electrical resistance signals. Thus, the hydrogel E-skins had the ability of quantitatively feeding back external stimuli through electrical resistance as well as visually mapping the stimulating sites by color variation. This dual-signal sensing provides the ability of visible-user interaction as well as antiinterference, endowing the multifunctional E-skin with great application prospects.


Assuntos
Celulose/química , Condutividade Elétrica , Hidrogéis/química , Cristais Líquidos , Dispositivos Eletrônicos Vestíveis , Cor , Fenômenos Ópticos
19.
Adv Exp Med Biol ; 1250: 35-48, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601936

RESUMO

Injectable in situ-forming hydrogels have been used clinically in diverse biomedical applications. These hydrogels have distinct advantages such as easy management and minimal invasiveness. The hydrogels are aqueous formulations, and a simple injection at the target site replaces a traditional surgical procedure. Here, we review injectable in situ-forming hydrogels that are formulated by physical and chemical methods to deliver proteins and peptides. Prospects for using in situ-forming hydrogels for several specific applications are also discussed.


Assuntos
Hidrogéis , Peptídeos , Proteínas , Sistemas de Liberação de Medicamentos , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Injeções , Peptídeos/administração & dosagem , Proteínas/administração & dosagem
20.
Adv Exp Med Biol ; 1250: 49-61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601937

RESUMO

A wide variety of hydrogels have been proposed for tissue engineering applications, cell encapsulation, and bioinks for bioprinting applications. Cell-laden hydrogel constructs rely on natural hydrogels such as alginate, agarose, chitosan, collagen, gelatin, fibroin, and hyaluronic acid (HA), as well as on synthetic hydrogels such as poloxamers (Pluronics®) and polyethylene glycol (PEG). Alginate has become more and more important in the last years, thanks to the possibility to prepare alginate hydrogels suitable for cell encapsulation mainly because of the mild and reversible cross-linking conditions. In this paper alginate will be described in detail with respect to its chemistry, cross-linking behavior, biocompatibility, manufacturing capacity, and possible modifications.


Assuntos
Alginatos , Encapsulamento de Células , Hidrogéis , Engenharia Tecidual , Tecidos Suporte , Alginatos/química , Bioimpressão , Hidrogéis/química , Tecidos Suporte/química
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