Hydrogel Shell Research Articles

Biocompatible hollow polymeric particles produced by a mild solvent- and template free strategy

Macroscopic hollow polymeric particles are attractive materials for various applications such as surgery, food industry, agriculture, etc. However, protocols reporting their synthesis have hitherto made use of organic solvents and/or sacrificial templates, compromising the encapsulation of different bioactive compounds and the process yield. Here, millimeter-size, hollow polymeric particles were synthesized, for the first time, in a solvent- and template free manner onto superhydrophobic surfaces (SHS). The particles were produced upon assembly and double superficial crosslinking of liquid droplets of DNA and methacrylamide chitosan aqueous solutions (CH:MA), leading to liquid-core particles with a hardened hydrogel shell. The particles displayed appealing physical and biological properties. The millimeter-size hydrogel shell, resulting from the double ionic/covalent crosslinking of CH:MA, endowed the hollow particles with softness to the touch and an outstanding structural stability against manipulation by hand and with forceps. Meanwhile, the liquid DNA core guaranteed a biocompatible cell encapsulation followed by a superior release and proliferation of viable cells, as compared to solid CH:MA particles prepared as a blank. Particles with these characteristics show promise for surgical protocols practiced in Tissue Engineering and Regenerative Medicine, where manipulable and biocompatible synthetic implants are often needed to supply living cells and other sensitive bioactive compounds.

A Cell-Mimicking Structure Converting Analog Volume Changes to Digital Colorimetric Output with Molecular Selectivity.

We herein report a three-component cell-mimicking structure with a peroxidase-like iron oxide nanozyme as the nucleus, a molecularly imprinted hydrogel shell as cytoplasm, and a lipid bilayer membrane. The structure was characterized by cryo and negative stain TEM and also by a calcein leakage test. By introducing charged monomers, the gel shell can swell or shrink in response to salt concentration. By lowering the salt concentration, the gradual "analog" gel volume change was reflected in a switch-like "digital" colorimetric output by the burst of membrane and oxidation of substrates such as 3,3',5,5'-tetramethylbenzidine (TMB). Controlled access was also achieved by using melittin to insert channels cross the membrane, and selective molecular transport was realized by the molecularly imprinted gel. The functions of each component are coupled, and this sophisticated tripartite structure provides a new platform for modular design of new materials. Our cell-mimicking structure is functional and it is complementary to the current protocell work that aims to understand the origin of life.

Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules

AbstractSurface modification with bioactive agents capable of combating thrombosis is a widely used strategy for developing antithrombotic biomaterials. However, exposure of the blood to the antithrombotic agent on the material surface may cause hemostatic disorders under normal conditions. Ideally an implanted biomaterial should respond appropriately on demand to a specific change in the physiologic environment, as happens in the body itself. In the present study, a thrombosis‐responsive surface coating with the ability to lyse fibrin as it forms is reported. The coating consists of nanocapsules (NCs) in which the fibrinolysis activator t‐PA is encapsulated in a thrombin‐degradable hydrogel shell. The t‐PA NCs are attached to several materials covalently through a polydopamine adhesive layer. The resulting surfaces are treated with the antifouling agent glutathione (GSH) to prevent further interactions with blood/plasma components. The t‐PA NCs/GSH‐coated surface is stable and remain inert in normal plasma environment while releasing t‐PA and promoting fibrinolysis when thrombin is present. The fibrinolytic activity increases with increasing thrombin concentration, and therefore presumably with the extent of thrombosis. This work constitutes the first report of an antithrombotic coating whose function is triggered and regulated, respectively, by the appearance of thrombin and the extent of coagulation.

Characterization and in vitro drug release properties of core–shell hydrogel prepared by gamma irradiation

ABSTRACTA hydrogel system was prepared based on core–shell approach for the delivery of trifluoperazine. Acrylonitrile (AN) core and methacrylic acid (MAA) shell copolymer were performed using gamma irradiation. The resulted system has been characterized by FTIR, TGA, TEM, and SEM techniques. The in vitro release study showed that the maximum drug released was 6.11 mg g−1 for AN–MAA copolymer through 120 min and 22.34 mg g−1 for AN-core–MAAc shell through 240 min. The results demonstrated that AN-core–MAAc had better properties than AN–MAA copolymer which means the preparation technique highly affects the properties of the system.

Publisher’s note

Macroscopic hollow polymeric particles are attractive materials for various applications such as surgery, food industry, agriculture, etc. However, protocols reporting their synthesis have hitherto made use of organic solvents and/or sacrificial templates, compromising the encapsulation of different bioactive compounds and the process yield. Here, millimeter-size, hollow polymeric particles were synthesized, for the first time, in a solvent- and template free manner onto superhydrophobic surfaces (SHS). The particles were produced upon assembly and double superficial crosslinking of liquid droplets of DNA and methacrylamide chitosan aqueous solutions (CH:MA), leading to liquid-core particles with a hardened hydrogel shell. The particles displayed appealing physical and biological properties. The millimeter-size hydrogel shell, resulting from the double ionic/covalent crosslinking of CH:MA, endowed the hollow particles with softness to the touch and an outstanding structural stability against manipulation by hand and with forceps. Meanwhile, the liquid DNA core guaranteed a biocompatible cell encapsulation followed by a superior release and proliferation of viable cells, as compared to solid CH:MA particles prepared as a blank. Particles with these characteristics show promise for surgical protocols practiced in Tissue Engineering and Regenerative Medicine, where manipulable and biocompatible synthetic implants are often needed to supply living cells and other sensitive bioactive compounds.

Stable in Bulk and Aggregating at the Interface: Comparing Core-Shell Nanoparticles in Suspension and at Fluid Interfaces.

Colloidal particles are extensively used to assemble materials from bulk suspensions or after adsorption and confinement at fluid interfaces (e.g., oil-water interfaces). Interestingly, and often underestimated, optimizing interactions for bulk assembly may not lead to the same behavior at fluid interfaces. In this work, we compare model composite nanoparticles with a silica core coated with a poly-N-isopropylacrylamide hydrogel shell in bulk aqueous suspensions and after adsorption at an oil-water interface. Bulk properties are analyzed by confocal differential dynamic microscopy, a recently developed technique that allows one to simultaneously obtain structural and dynamical information up to high volume fractions. The results demonstrate excellent colloidal stability and the absence of aggregation in all cases. The behavior at the interface, investigated by a range of complementary approaches, is instead different. The same hydrogel shells that stabilize the particles in the bulk deform at the interface and induce attractive capillary interactions that lead to aggregation even at very low area fractions (surface coverage). Upon further compression of a particle-laden interface, a structural transition is observed where closely packed particle aggregates form. These findings emphasize the manifestation of different, and possibly unexpected, responses for sterically stabilized nanoparticles in the bulk and upon interfacial confinement.

Synthesis of self-suspending silica proppants using photoactive hydrogels

Micro and mesoscale particles in fluids are widely used from hydrocarbon extraction to drug delivery applications. Of interest are silica particles that are used as proppants for the extraction of natural gas from underground reserves. These particles have the tendency to settle out or aggregate in slurries, resulting in hindered transport. This in turn, necessitates requires high pressure pumping or additives, resulting in various environmental concerns and increased costs. As an alternative to using lighter proppant particles, here we report on a facile procedure to create self-suspending particles formed by a water swellable hydrogel shell. We graft photoactive polyethylene glycol hydrogels to large, non-spherical silica particles using a UV polymerization procedure. The proppant particles formed are stable with a high degree of hydration and reduced apparent density. A significant drop in density in comparison to unmodified particles is shown that can reduce the settling velocity and thereby, reduce hindered transport. The experimentally obtained settling velocities are in good agreement with theoretical models. The ability to tune particle density has implications in industrial applications to improve environmental impact, efficiency and productivity.

Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery.

Development of high-fidelity three-dimensional (3D) models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumors, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis and for developing effective therapeutic strategy to fight against cancer.

Interwoven Aligned Conductive Nanofiber Yarn/Hydrogel Composite Scaffolds for Engineered 3D Cardiac Anisotropy.

Mimicking the anisotropic cardiac structure and guiding 3D cellular orientation play a critical role in designing scaffolds for cardiac tissue regeneration. Significant advances have been achieved to control cellular alignment and elongation, but it remains an ongoing challenge for engineering 3D cardiac anisotropy using these approaches. Here, we present a 3D hybrid scaffold based on aligned conductive nanofiber yarns network (NFYs-NET, composition: polycaprolactone, silk fibroin, and carbon nanotubes) within a hydrogel shell for mimicking the native cardiac tissue structure, and further demonstrate their great potential for engineering 3D cardiac anisotropy for cardiac tissue engineering. The NFYs-NET structures are shown to control cellular orientation and enhance cardiomyocytes (CMs) maturation. 3D hybrid scaffolds were then fabricated by encapsulating NFYs-NET layers within hydrogel shell, and these 3D scaffolds performed the ability to promote aligned and elongated CMs maturation on each layer and individually control cellular orientation on different layers in a 3D environment. Furthermore, endothelialized myocardium was constructed by using this hybrid strategy via the coculture of CMs on NFYs-NET layer and endothelial cells within hydrogel shell. Therefore, these 3D hybrid scaffolds, containing NFYs-NET layer inducing cellular orientation, maturation, and anisotropy and hydrogel shell providing a suitable 3D environment for endothelialization, has great potential in engineering 3D cardiac anisotropy.

A novel composite hydrogel initiated by Spinacia oleracea L. extract on Hela cells for localized photodynamic therapy

In this study, the poly (ethylene glycol) double acrylates (PEGDA) was first initiated by Spinacia oleracea L. extract (SOLE) to in situ form a polymer hydrogel shell on Hela cells with near infra-red irradiation. The SOLE was also a natural photosensitizer for photodynamic therapy of tumor. The use of SOLE is simple, eco-friendly, low cost, and convenient. More importantly, the PEGDA/SOLE composite hydrogel shell on Hela cells not merely prevents SOLE from diffusing to normal tissue for reducing the side effects, but also keeps high SOLE concentration on tumor cell for improving the antitumor effect. Such a hydrogel system has good biocompatibility and exhibits high therapeutic efficacy. This study extended the application of the SOLE/PEGDA gel in photodynamic therapy.

An investigation of obtaining patterns, structure and diffusion properties of biomedical purpose hydrogel membranes

The obtaining patterns of hydrogel membrane coatings based on 2-hydroxyethylmethacrylate/polyvinylpyrrolidone copolymers were investigated. Temperature modes of their synthesis were justified and efficient initiating system – a complex of polyvinylpyrrolidone with iron sulfate, which allows low-temperature synthesis was selected. The structural parameters of the grid and membrane permeability for model substances (electrolytes) and medicines (on the example of sodium diclofenac) were studied. The interrelation of structure and composition of hydrogels with their diffusion-transport properties was established. The mechanism of components transfer from encapsulated hydrogel particles through the membrane was described. This mechanism includes the steps of swelling of the hydrogel membrane, molecular diffusion inside the capsule, mass transfer through the membrane to the surrounding solution. The model of mass transfer of the ensemble of spherical particles coated with a polymeric hydrogel shell was proposed. The model makes it possible to predict the duration and rate of release of the target component from encapsulated particles. The process flow diagram of hydrogel membrane coatings forming was developed to create encapsulated forms of sustained drug release.

All-in-one 3D printed microscopy chamber for multidimensional imaging, the UniverSlide

While live 3D high resolution microscopy techniques are developing rapidly, their use for biological applications is partially hampered by practical difficulties such as the lack of a versatile sample chamber. Here, we propose the design of a multi-usage observation chamber adapted for live 3D bio-imaging. We show the usefulness and practicality of this chamber, which we named the UniverSlide, for live imaging of two case examples, namely multicellular systems encapsulated in sub-millimeter hydrogel shells and zebrafish larvae. We also demonstrate its versatility and compatibility with all microscopy devices by using upright or inverted microscope configurations after loading the UniverSlide with fixed or living samples. Further, the device is applicable for medium/high throughput screening and automatized multi-position image acquisition, providing a constraint-free but stable and parallelized immobilization of the samples. The frame of the UniverSlide is fabricated using a stereolithography 3D printer, has the size of a microscopy slide, is autoclavable and sealed with a removable lid, which makes it suitable for use in a controlled culture environment. We describe in details how to build this chamber and we provide all the files necessary to print the different pieces in the lab.

A novel 5-FU/rGO/Bce hybrid hydrogel shell on a tumor cell: one-step synthesis and synergistic chemo/photo-thermal/photodynamic effect

A novel drug-loaded inorganic nanoparticle–biomolecule hybrid hydrogel shell on tumor cells was firstly prepared.

Microcapsules with a permeable hydrogel shell and an aqueous core continuously produced in a 3D microdevice by all-aqueous microfluidics

We report the continuous production of microcapsules composed of an aqueous core and permeable hydrogel shell, made stable by the controlled photo-cross-linking of the shell of an all-aqueous double emulsion.

Compression of hard core-soft shell nanoparticles at liquid-liquid interfaces: influence of the shell thickness.

Soft hydrogel particles show a rich structural and mechanical behaviour compared to hard particles, both in bulk and when confined in two dimensions at a fluid interface. Moreover, encapsulation into hydrogel shells makes it possible to transfer the tunability of soft steric interactions to hard nanoparticle cores, which bear interest for applications, e.g. in terms of optical, magnetic and reinforcement properties. In this work, we investigate the microstructures formed by hard core-soft shell particles at liquid-liquid interfaces upon compression. We produced model particles with the same silica core and systematically varied the shell-to-core ratio by synthesising shells with three different thicknesses. These particles were spread at an oil-water interface in a Langmuir-Blodgett trough and continuously transferred onto a solid support during compression. The transferred microstructures were analysed by atomic force and scanning electron microscopy. Quantitative image analysis provided information on the particle packing density, the inter-particle distance, and the degree of order of the monolayers. We discovered several essential differences compared to purely soft hydrogel particles, which shed light on the role played by the hard cores in the assembly and compression of these composite monolayers.

PH- and ligand-induced release of loads from DNA-acrylamide hydrogel microcapsules.

Herein, a method to construct stimuli-responsive DNA-acrylamide-based hydrogel microcapsules has been presented. This method involves the use of polyacrylamide chains modified with predesigned nucleic acid hairpin units and optionally single-strand tethers that provide the required hybridization and recognition functions to yield substrate-loaded stimuli-responsive hydrogel-based microcapsules. The synthesis of the microcapsules involves the loading of CaCO3 microparticles with the respective load substrates and the functionalization of the CaCO3 template particles with nucleic acid promoter units. In the presence of the hairpin-modified acrylamide chains, the promoter units induce the hybridization chain reaction (HCR), which leads to the formation of a hydrogel coating, which, after the dissociation of the CaCO3 cores, yields substrate-loaded stimuli-responsive hydrogel microcapsules. One of the microcapsule systems includes, in the hairpin-modified acrylamide constructs, and in the subsequent HCR-generated hydrogel shells, the caged sequences of anti-ATP or anti-cocaine aptamers. In the presence of ATP or cocaine, the duplex-caged aptamer sequences are separated via the formation of ATP- or cocaine-aptamer complexes, which results in the partial separation of the microcapsules and the release of the loads. The second type of microcapsule is cooperatively stabilized by bridges generated by HCR and pH-sensitive duplex units. Under acidic conditions, the pH-sensitive bridges dissociate via the formation of i-motif structures, which results in an increase in the fluidity of the microcapsule shells and the release of the loads. Preliminary studies indicate that ATP- or pH-responsive microcapsules loaded with the anticancer drug, doxorubicin, have a selective cytotoxic effect on MDA-MB-231 cancer cells.

Electrospray-mediated preparation of compositionally homogeneous core–shell hydrogel microspheres for sustained drug release

Compositionally homogeneous core–shell hydrogel microspheres were prepared for sustained drug release.

Photonic-crystal hydrogels with a rapidly tunable stop band and high reflectivity across the visible

We present a new type of hydrogel photonic crystal with a stop band that can be rapidly modulated across the entire visible spectrum. We make these materials by using a high-molecular-weight polymer to induce a depletion attraction between polystyrene-poly(N-isopropylacrylamide-co-bisacrylamide-co-acrylic acid) core-shell particles. The resulting crystals display a stop band at visible wavelengths that can be tuned with temperature at a rate of 60 nm/s, nearly three orders of magnitude faster than previous photonic-crystal hydrogels. Above a critical concentration of depleting agent, the crystals do not melt even at 40 degrees Celsius. As a result, the stop band can be modulated continuously from red (650 nm) to blue (450 nm), with nearly constant reflectivity throughout the visible spectrum. The unusual thermal stability is due to the polymer used as the depleting agent, which is too large to enter the hydrogel mesh and therefore induces a large osmotic pressure that holds the particles together. The fast response rate is due to the collective diffusion coefficient of our hydrogel shells, which is more than three orders of magnitude larger than that of conventional bulk hydrogels. Finally, the constant reflectivity from red (650 nm) to blue (450 nm) is due to the core-shell design of the particles, whose scattering is dominated by the polystyrene cores and not the hydrogel. These findings provide new insights into the design of responsive photonic crystals for display applications and tunable lasers.

Frontispiece: Bilayer Networks within a Hydrogel Shell: A Robust Chassis for Artificial Cells and a Platform for Membrane Studies

Frontispiece: Bilayer Networks within a Hydrogel Shell: A Robust Chassis for Artificial Cells and a Platform for Membrane Studies

Bilayer Networks within a Hydrogel Shell: A Robust Chassis for Artificial Cells and a Platform for Membrane Studies

AbstractThe ability to make artificial lipid bilayers compatible with a wide range of environments, and with sufficient structural rigidity for manual handling, would open up a wealth of opportunities for their more routine use in real‐world applications. Although droplet interface bilayers (DIBs) have been demonstrated in a host of laboratory applications, from chemical logic to biosynthesis reaction vessels, their wider use is hampered by a lack of mechanical stability and the largely manual methods employed in their production. Multiphase microfluidics has enabled us to construct hierarchical triple emulsions with a semipermeable shell, in order to form robust, bilayer‐bound, droplet networks capable of communication with their external surroundings. These constructs are stable in air, water, and oil environments and overcome a critical obstacle of achieving structural rigidity without compromising environmental interaction. This paves the way for practical application of artificial membranes or droplet networks in diverse areas such as medical applications, drug testing, biophysical studies and their use as synthetic cells.