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Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modeling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues is becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit a behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging-on-a-chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.
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Matriz Extracelular Descelularizada , Envelhecimento da Pele , Humanos , Idoso , Materiais Biocompatíveis/farmacologia , Hidrogéis , ColágenoRESUMO
Liquid crystal macrocycles (LCMs) combine the unique properties of liquid crystals with those associated with macrocyclic compounds-shape persistence and the capability of hosting small molecules. Herein, we investigate the grafting of coumarin-containing promesogenic moieties to pillar[5]arene as a strategy to obtain multifunctional LCMs. Pillar[5]arenes containing 10 and 30 coumarin units are glassy materials with nematic mesomorphism. Moreover, the coumarin moieties afford the pillar[5]arene derivatives with enhanced film-forming and photoresponsive properties. Photodimerization of the coumarin moieties results in cross-linked polymer networks, which can be used as alignment layers. Therefore, liquid-crystal coumarin-containing pillar[5]arenes represent a significant addition to the family of LCMs and may become useful for the development of engineered, hierarchical structures and materials.
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Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing, and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (Keq up to 1014 M-2). Using stopped-flow spectrofluorimetry, association rate constants were observed to approach the diffusion limit and were found to be insensitive to the structure of the guest. Conversely, the dissociation rate constants of the ternary complexes varied dramatically with the guest structure and were correlated with the thermodynamic binding selectivity. Hence differing molecular features were found to contribute to the associative and dissociative processes, mimicking naturally occurring reactions and giving rise to a decoupling of these kinetic parameters. Moreover, we demonstrate the ability to exploit these phenomena and selectively perturb the associative process with external stimuli (e.g., viscosity and pressure). Significantly, these complexes exhibit increased binding equilibria with increasing pressure, with important implications for the application of the CB[8] ternary complex for the formation of hydrogels, as these gels exhibit unprecedented pressure-insensitive rheological properties. A high degree of flexibility therefore exists in the design of host-guest systems with tunable kinetic and thermodynamic parameters for tailor-made applications across a broad range of fields.
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Cucurbit[8]uril (CB[8]) heteroternary complexes display certain characteristics making them well-suited for molecular level adhesives. In particular, careful choice of host-guest binding pairs enables specific, fully reversible adhesion. Understanding the effect of the environment is also critical when developing new molecular level adhesives. Here we explore the binding forces involved in the methyl viologen·CB[8]·naphthol heteroternary complex using single-molecule force spectroscopy (SMFS) under a variety of conditions. From SMFS, the interaction of a single ternary complex was found to be in the region of 140 pN. Additionally, a number of surface interactions could be readily differentiated using the SMFS technique allowing for a deeper understanding of the dynamic heteroternary CB[8] system on the single-molecule scale.
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Cucurbit[8]uril (CB[8])-mediated complexation of a dicationic azobenzene in water allows for the light-controlled encapsulation of a variety of second guest compounds, including amino acids, dyes, and fragrance molecules. Such controlled guest sequestration inside the cavity of CB[8] enables the regulation of the thermally induced phase transition of poly(N-isopropylacrylamide)-which is not photosensitive-thus demonstrating the robustness and relevancy of the light-regulated CB[8] complexation.
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Compostos Azo/química , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/síntese química , Acrilamidas , Resinas Acrílicas/química , Algoritmos , Aminoácidos/química , Compostos Azo/efeitos da radiação , Hidrocarbonetos Aromáticos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/efeitos da radiação , Corantes/química , Imidazóis/química , Luz , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Perfumes , Polímeros , Raios Ultravioleta , ÁguaRESUMO
The rational design of a flexible molecular box, oAzoBox4+ , incoporating both photochromic and supramolecular recognition motifs is described. We exploit the EâZ photoisomerization properties of azobenzenes to alter the shape of the cavity of the macrocycle upon absorption of light. Imidazolium motifs are used as hydrogen-bonding donor components, allowing for sequestration of small molecule guests in acetonitrile. Upon EâZ photoisomerization of oAzoBox4+ the guest is expelled from the macrocyclic cavity.
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We report the self-assembly of a series of highly charged supramolecular complexes in aqueous media composed of cyclobis(4,4'-(1,4-phenylene)bispyridine-p-phenylene)tetrakis(chloride) (ExBox) and three dicationic perylene diimides (PDIs). Efficient energy transfer (ET) is observed between the host and guests. Additionally, we show that our hexacationic complexes are capable of further complexation with neutral cucurbit[7]uril (CB[7]), producing a 3-polypseudorotaxane via the self-assembly of orthogonal recognition moieties. ExBox serves as the central ring, complexing to the PDI core, while two CB[7]s behave as supramolecular stoppers, binding to the two outer quaternary ammonium motifs. The formation of the 3-polypseudorotaxane results in far superior photophysical properties of the central PDI unit relative to the binary complexes at stoichiometric ratios. Lastly, we also demonstrate the ability of our binary complexes to act as a highly selective chemosensing ensemble for the neurotransmitter melatonin.
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Hidrocarbonetos Aromáticos com Pontes/química , Imidas/química , Perileno/análogos & derivados , Polímeros/química , Compostos de Piridínio/química , Cátions/química , Transferência de Energia , Estrutura Molecular , Perileno/químicaRESUMO
A dynamic-covalent metal-containing polymer was synthesized by the condensation of linear diamine and dialdehyde subcomponents around copper(I) templates in the presence of bidentate phosphine ligands. In solution, the red polymers undergo a sol-gel transition upon heating to form a yellow gel, a process that can be either reversible or irreversible depending on the solvent used. When fabricated into a light-emitting electrochemical cell (LEC), the polymer emits infrared light at low voltage. As the voltage is increased, a blue shift in the emission wavelength is observed until yellow light is emitted, a process which is gradually reversed over time upon lowering the voltage. The mechanism underlying these apparently disparate responses is deduced to be due to loss of the copper phosphine complex from the polymer.
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DNA nanotechnology leverages Watson-Crick-Franklin base-pairing interactions to build complex DNA-based nanostructures (DNS). Due to DNA specific self-assembly properties, DNS can be designed with a total control of their architecture, which has been demonstrated to have an impact on the overall DNS features. Indeed, structural properties such as the shape, size and flexibility of DNS can influence their biostability as well as their ability to internalise into cells. We present here two series of simple DNS with small and precise variations related to their length or flexibility and study the influence that these structural changes have on their overall properties as drug nanocarriers. Results indicate that shorter and more flexible DNS present higher stability towards nuclease degradation. These structural changes also have a certain effect on their cell internalisation ability and drug release rate. Consequently, drug-loaded DNS cytotoxicity varies according to the design, with lower cell viability values obtained in the DNS exhibiting faster drug release and larger cell interaction rates. In summary, small changes in the structure of simple DNS can have an influence on their overall capabilities as drug nanocarriers. The effects reported here could guide the design of simple DNS for future therapeutic uses.
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Nanoestruturas , Nanoestruturas/química , DNA/química , Nanotecnologia/métodos , Sobrevivência CelularRESUMO
Underwater organisms exhibit sophisticated propulsion mechanisms, enabling them to navigate fluid environments with exceptional dexterity. Recently, substantial efforts have focused on integrating these movements into soft robots using smart shape-changing materials, particularly by using light for their propulsion and control. Nonetheless, challenges persist, including slow response times and the need of powerful light beams to actuate the robot. This last can result in unintended sample heating and potentially necessitate tracking specific actuation spots on the swimmer. To tackle these challenges, new azobenzene-containing photopolymerizable inks are introduced, which can be processed by extrusion printing into liquid crystalline elastomer (LCE) elements of precise shape and morphology. These LCEs exhibit rapid and significant photomechanical response underwater, driven by moderate-intensity ultraviolet (UV) and green light, being the actuation mechanism predominantly photochemical. Inspired by nature, a biomimetic four-lapped ephyra-like LCE swimmer is printed. The periodically illumination of the entire swimmer with moderate-intensity UV and green light, induces synchronous lappet bending toward the light source and swimmer propulsion away from the light. The platform eliminates the need of localized laser beams and tracking systems to monitor the swimmer's motion through the fluid, making it a versatile tool for creating light-fueled robotic LCE free-swimmers.
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The desire to continually reduce the lower limits of semiconductor integrated circuit (IC) fabrication methods continues to inspire interest in unimolecular electronics as a platform technology for the realization of future (opto)electronic devices. However, despite successes in developing methods for the construction and measurement of single-molecule and large-area molecular junctions, exercising control over the precise junction geometry remains a significant challenge. Here, host-guest complexes of the wire-like viologen derivative 1,1'-bis(4-(methylthio)-phenyl)-[4,4'-bipyridine]-1,1'-diium chloride ([1][Cl]2) and cucurbit[7]uril (CB[7]) have been self-assembled in a regular pattern over a gold substrate. Subsequently, ligandless gold nanoparticles (AuNPs) synthesized in situ are deposited over the host-guest array. The agreement between the conductance of individual mono-molecular junctions, appropriately chosen as a function of the AuNP diameter, within this array determined by conductive probe atomic force microscope (c-AFM) and true single-molecule measurements for a closely similar host-guest complex within a scanning tunneling microscope break-junction (STM-BJ) indicates the formation of molecular junctions derived from these host-guest complexes without deleterious intermolecular coupling effects.
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Herein we report the photocontrol of cucurbit[8]uril (CB[8])-mediated supramolecular polymerization of azobenzene-containing monomers. The CB[8] polymers were characterized both in solution and in the solid state. These host-guest complexes can be reversibly switched between highly thermostable photostationary states. Moreover, a remarkable stabilization of Z-azobenzene was achieved by CB[8] complexation, allowing for structural characterization in the solid state.
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Viologen end and side-chain functional macromolecules are synthesized through a high-yielding, copper-mediated azide-alkyne [3+2] cycloaddition reaction. Specifically, poly(ethylene glycol) (PEG) and the C-terminus of a model oligopeptide are quantitatively end-coupled to a viologen moiety as confirmed by (1) H NMR, gel permeation chromatography (GPC), and mass spectrometry (MS). Side-chain functionalization of a styrene backbone is also readily achieved forming a polyelectrolyte species and demonstrating the applicability of this method across a range of macromolecular species. It is found that viologen itself slows the reaction and that careful choice of counter ions, the specific chelating ligand for the copper-mediated reaction, solvent, as well as the amount of copper also play major roles in the time to completion of the reaction and hence the yield. Macromolecules formed through this route bind effectively with supramolecular host molecule cucurbit[8]uril allowing for controlled solution-phase self-assembly, for example of a supramolecular star polymer.
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Alcinos/química , Azidas/química , Viologênios/química , Catálise , Cromatografia em Gel , Cobre/química , Reação de Cicloadição , Eletrólitos/química , Espectroscopia de Ressonância Magnética , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Polietilenoglicóis/químicaRESUMO
The supramolecular crosslinking of polymer chains in water by specific, directional and dynamic non-covalent interactions has led to the development of novel supramolecular polymeric hydrogels. These aqueous polymeric networks constitute an interesting class of soft materials exhibiting attractive properties such as stimuli-responsiveness and self-healing arising from their dynamic behaviour and that are crucial for a wide variety of emerging applications. We present here a critical review summarising the formation of dynamic polymeric networks through specific non-covalent interactions, with a particular emphasis on those systems based on host-guest complex formation, as well as the characterisation of their physical characteristics. Aqueous supramolecular chemistry has unlocked a versatile toolbox for the design and fine-tuning of the material properties of these hydrogels (264 references).
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Recently, significant advances have been achieved to precisely program the response of liquid crystal elastomers (LCEs) through extrusion-based additive manufacturing techniques; however, important challenges remain, especially when well-defined scaffolds based on ultrafine fibers are required. Here the melt electrowriting of reactive liquid crystalline inks, leading, after ultraviolet-light-induced crosslinking, to digitally positioned uniform LCE fibers with diameters ranging from hundreds of nanometers to tens of micrometers is presented, which is hardly accessible with conventional extrusion-based printing techniques. The electrowriting process induces the preferential alignment of the mesogens parallel to the fiber's axis. Such an alignment, defined by the printing path, determines the mechanical response of the crosslinked material upon stimulation. This manufacturing platform allows the preparation of open square lattice scaffolds with ultrafine fibers (a few micrometers in diameter), periods as small as 90 µm, and well-defined morphology. Additionally, the combination of accurate fiber stacking (up to 50 layers) and fiber fusion between layers leads to unprecedented microstructures composed of high-aspect-ratio LCE thin walls. The possibility of digitally controlling the printing of fibers allows the preparation complex fiber-based scaffolds with programmed and reversible shape-morphing, thus opening new avenues to prepare miniaturized actuators and smart structures for soft robotics and biomedical applications.
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Mechanical interactions between cells and their microenvironment play an important role in determining cell fate, which is particularly relevant in metastasis, a process where cells invade tissue matrices with different mechanical properties. In vitro, type I collagen hydrogels have been commonly used for modeling the microenvironment due to its ubiquity in the human body. In this work, the combined influence of the stiffness of these hydrogels and their ultrastructure on the migration patterns of HCT-116 and HT-29 spheroids are analyzed. For this, six different types of pure type I collagen hydrogels by changing the collagen concentration and the gelation temperature are prepared. The stiffness of each sample is measured and its ultrastructure is characterized. Cell migration studies are then performed by seeding the spheroids in three different spatial conditions. It is shown that changes in the aforementioned parameters lead to differences in the mechanical stiffness of the matrices as well as the ultrastructure. These differences, in turn, lead to distinct cell migration patterns of HCT-116 and HT-29 spheroids in either of the spatial conditions tested. Based on these results, it is concluded that the stiffness and the ultrastructural organization of the matrix can actively modulate cell migration behavior in colorectal cancer spheroids.
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The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers.
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Acrilamidas , Antibióticos Antineoplásicos , Doxorrubicina , Metacrilatos , Nanopartículas/química , Nylons , Polímeros , Acrilamidas/química , Acrilamidas/farmacologia , Resinas Acrílicas , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Células HeLa , Humanos , Metacrilatos/química , Metacrilatos/farmacologia , Nylons/química , Nylons/farmacologia , Polímeros/química , Polímeros/farmacologiaRESUMO
We report the formation of cylindrical micelles, sheet-like micelles, tubular micelles, as well as polymer vesicles by a new series of amphiphilic linear-dendritic block-copolymers (BCs). The BCs, noted as PEGm-AZOn, are composed of poly(ethylene glycol) (PEG) chains of different molecular weights as hydrophilic blocks and the first four generations of azobenzene-containing dendrons based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) as hydrophobic blocks (m represents the degree of polymerization of PEG, and n is the number of azobenzene units at the periphery of dendron). The polymeric aggregates were formed by adding water to solutions of the BCs in dioxane. The micellar dispersions in water were finally obtained by removing dioxane via dialysis against water. The morphology of the micellar self-assemblies was studied by transmission electron microscopy (TEM), cryo-electron microscopy (cryo-TEM), and atomic force microscopy (AFM). A generation-dependent aggregation behavior was found for the series of BCs PEG45-AZOn. Core-shell structured nanofibers with an inner diameter of 8 nm were observed for the copolymer PEG45-AZO2 (hydrophilic/hydrophobic weight ratio equal to 67/33). Lyotropic liquid crystalline behavior was detected for the aqueous solution of the nanofibers. The coexistence of sheet-like aggregates and tubular micelles was detected for the copolymer PEG45-AZO8 in which the number of cyanoazobenzene units is increased to 8 (hydrophilic/hydrophobic weight ratio equal to 33/67). The tubular micelles could be intermediates in the sheet-like aggregate-to-vesicle transition. Polymer vesicles (polymersomes) with a diameter in the range 300-800 nm were observed for the copolymer PEG45-AZO16 (hydrophilic/hydrophobic weight ratio equal to 20/80). The membrane of the sheet-like aggregates, tubular micelles, and polymersomes was shown to have a bilayer structure, as revealed by cryo-TEM. UV illumination of the aqueous polymersome dispersion induced the formation of wrinkles in the vesicle membrane, thus showing that this type of polymeric aggregate is photoresponsive.