Microgel Concentration Research Articles

Microgels With Electrostatically Controlled Molecular Affinity to Direct Morphogenesis.

Concentration gradients of soluble signaling molecules-morphogens-determine the cellular organization in tissue development. Morphogen-releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulfated glycosaminoglycans (sGAGs) in morphogen signaling in vivo, a library of sGAG-based microgels is developed and designated as µGel Units to Instruct Development (µGUIDEs). Adjustment of the microgel's sGAG sulfation patterns and concentration enabled the programming of electrostatic affinities that control the release of morphogens. Based on computational analyses of molecular transport processes, µGUIDEs provided unprecedented precision in the spatiotemporal modulation of vascular endothelial growth factor (VEGF) gradients in a microgel-in-gel vasculogenesis model and kidney organoid cultures. The versatile approach offers new options for creating morphogen signaling centers to advance the understanding of tissue and organ development.

Formation of Self-Healing Granular Eutectogels through Jammed Carbopol Microgels in Supercooled Deep Eutectic Solvent.

Typically, gel-like materials consist of a polymer network structure in a solvent. In this work, a gel-like material is developed in a deep eutectic solvent (DES) without the presence of a polymer network, achieved simply by adding microgels. The DES is composed of choline chloride and citric acid and remains stably in a supercooled state at room temperature, exhibiting Newtonian fluid behavior with high viscosity. When the microgel (Carbopol) concentration exceeds 2 wt %, the DES undergoes a transition from a liquid to a soft gel state, characterized as a granular eutectogel. The soft gel characteristics of eutectogels exhibit a yield stress, and their storage moduli exceed the loss moduli. The yield stress and storage moduli are observed to increase with increasing microgel concentration. In contrast, the ion conductivity decreases with increasing microgel concentration but eventually levels off. Because the eutectogel can dissolve completely in excess water, it is a physical gel-like material, attributed to the densely packed structure of microgels in the supercooled DES. Due to the absence of networks, the granular eutectogel has the capability to self-heal simply by being pushed together after being cut into two pieces.

Ultra-stable Pickering liquid crystal-in-water emulsions decorated with thermoresponsive soft microgels and their response to aqueous analytes

This work presents an extensive investigation of the Pickering stabilization of liquid crystal (LC)-in-water emulsions using soft nanometer-sized colloidal poly(N-isopropylacrylamide) (PNIPAM) microgel particles and the responsivity of the PNIPAM microgel-stabilized Pickering LC droplet-based assembly towards amphiphilic analytes. The evolution of size and stability of LC droplets with microgel concentration are found to be dependent on the emulsifier-regime. Despite microgel coating, the LC-water interface remains accessible to model analytes such as anionic sodium dodecyl sulfate (SDS) and cationic dodecyltrimethylammonium bromide (DTAB). The analytes can pass through the interfacial pores and/or meshes of porous microgels to induce a bipolar-to-radial ordering transition within the droplets. The dose-response behaviour is largely influenced by the initial microgel concentration, type of analytes and interfacial layer (charge), and the number of droplets exposed to the analytes. The PNIPAM microgel-coated LC droplets notably exhibited enhanced sensitivity under conditions promoting electrostatic attractive interactions between the interfacial microgel layer and analytes. Overall, the results highlight the potential of Pickering LC-in-water emulsions for reliable and quantitative analysis of aqueous analytes, thus opening up new avenues toward the development of droplet-based optical sensors.

Fibrin Hydrogels Reinforced by Reactive Microgels for Stimulus-Triggered Drug Administration.

Tissue engineering is a steadily growing field of research due to its wide-ranging applicability in the field of regenerative medicine. Application-dependent mechanical properties of a scaffold material as well as its biocompatibility and tailored functionality represent particular challenges. Here the properties of fibrin-based hydrogels reinforced by functional cytocompatible poly(N-vinylcaprolactam)-based (PVCL) microgels are studied and evaluated. The employment of temperature-responsive microgels decorated by epoxy groups for covalent binding to the fibrin is studied as a function of cross-linking degree within the microgels, microgel concentration, as well as temperature. Rheology reveals a strong correlation between the mechanical properties of the reinforced fibrin-based hydrogels and the microgel rigidity and concentration. The incorporated microgels serve as cross-links, which enable temperature-responsive behavior of the hydrogels, and slow down the hydrogel degradation. Microgels can be additionally used as carriers for active drugs, as demonstrated for dexamethasone. The microgels' temperature-responsiveness allows for triggered release of payload, which is monitored using a bioassay. The cytocompatibility of the microgel-reinforced fibrin-based hydrogels is demonstrated by LIVE/DEAD staining experiments using human mesenchymal stem cells. The microgel-reinforced hydrogels are a promising material for tissue engineering, owing to their superior mechanical performance and stability, possibility of drug release, and retained biocompatibility.

Modeling microgel swelling: Influence of chain finite extensibility.

Microgels exhibit the ability to undergo reversible swelling in response to shifts in environmental factors that include variations in temperature, concentration, and pH. While several models have been put forward to elucidate specific aspects of microgel swelling and its impact on bulk behavior, a consistent theoretical description that chains throughout the microscopic degrees of freedom with suspension properties and deepens into the full implications of swelling remains a challenge yet to be met. In this work, we extend the mean-field swelling model of microgels from Denton and Tang [J. Chem. Phys. 145, 164901 (2016)] to include the finite extensibility of the polymer chains. The elastic contribution to swelling in the original work is formulated for Gaussian chains. By using the Langevin chain model, we modify this elastic contribution in order to account for finite extensibility effects, which become prominent for microgels containing highly charged polyelectrolytes and short polymer chains. We assess the performance of both elastic models, namely for Gaussian and Langevin chains, comparing against coarse-grained bead-spring simulations of ionic microgels with explicit electrostatic interactions. We examine the applicability scope of the models under a variation of parameters, such as ionization degree, microgel concentration, and salt concentration. The models are also tested against experimental results. This work broadens the applicability of the microgel swelling model toward a more realistic description, which brings advantages when describing the suspensions of nanogels and weak-polyelectrolyte micro-/nanogels.

Mechanochromic Hydrogel Fibers with Multiple Fluorescent Colors.

Mechanochromic polymers can change their color in response to external force and have shown promising applications in stress sensing and failure warning. They are usually obtained as thin films or bulky specimens. The mechanochromic fibers, which can be used to make smart fabrics, have been seldom reported due to the lack of efficient fabrication techniques. In this work, a general method using photo-polymerization of microgel solution in a template tube to produce mechanochromic hydrogel fibers is reported. The obtained hydrogel fibers can generate visible and fluorescent color changes upon deformation. The diameter of the mechanochromic fibers can be easily adjusted by using different template tubes. The mechanochromic fibers can be fabricated as long as 1 m. By reducing the fiber diameter or increasing the microgel concentration, the mechanical properties of the mechanochromic fibers can be improved, leading to more obvious mechanochromic behavior. The polymethacrylate (PMA) is further used to coat the hydrogel fibers, prevent the loss of water in the fibers, and increase the storage time. The mechanochromic fibers with multiple fluorescent colors are further fabricated by utilizing different microgel solutions. This work provides an easy and effective method to fabricate mechanochromic fibers with different color change abilities.

Monte Carlo simulation of the ionization and uptake behavior of cationic oligomers into pH-responsive polyelectrolyte microgels of opposite charge - a model for oligopeptide uptake and release.

External stimuli can tune the uptake and release of guest molecules in microgels. Especially their pH responsiveness makes microgels exciting candidates for drug delivery systems. When both microgel and guest molecules are pH-responsive, predicting the electrostatically driven uptake can be complex since the ionization depends on many parameters. In this work, we performed Metropolis Monte Carlo simulations while systematically varying the pK of the monomers, the concentrations of microgel and guest molecules to obtain a better understanding of the uptake of weak cationic oligomers as a model for oligopeptides into a weak anionic polyelectrolyte microgel. Further, we varied the chain length of the oligomers. The polyelectrolyte networks can take up oligomers when both the network and the oligomers are charged. The presence of both species in the system leads to a mutual enhancement of their ionization. The uptake induces a release of counterions and results in complex formation between the oligomers and the network, leading to the collapse of the networks. Longer oligomers enhance the ionization of the network and, therefore, the complexation. A higher microgel concentration increases the uptake only around the isoelectric point but prevents the uptake due to lower entropy gain at counterion release at higher pH. The results give an insight into the uptake of cationic oligomers into oppositely charged polyelectrolyte microgels and provide hints for the design of anionic microgels as carriers for guest molecules e.g. antimicrobial peptides.

Osmotic swelling behavior of surface-charged ionic microgels.

In recent years, ionic microgels have garnered much attention due to their unique properties, especially their stimulus-sensitive swelling behavior. The tunable response of these soft, permeable, compressible, charged colloidal particles is increasingly attractive for applications in medicine and biotechnologies, such as controlled drug delivery, tissue engineering, and biosensing. The ability to model and predict variation of the osmotic pressure of a single microgel with respect to changes in particle properties and environmental conditions proves vital to such applications. In this work, we apply both nonlinear Poisson-Boltzmann theory and molecular dynamics simulation to ionic microgels (macroions) in the cell model to compute density profiles of microions (counterions, coions), single-microgel osmotic pressure, and equilibrium swelling ratios of spherical microgels whose fixed charge is confined to the macroion surface. The basis of our approach is an exact theorem that relates the electrostatic component of the osmotic pressure to the microion density profiles. Close agreement between theory and simulation serves as a consistency check to validate our approach. We predict that surface-charged microgels progressively deswell with increasing microgel concentration, starting well below close packing, and with increasing salt concentration, in qualitative agreement with experiments. Comparison with previous results for microgels with fixed charge uniformly distributed over their volume demonstrates that surface-charged microgels deswell more rapidly than volume-charged microgels. We conclude that swelling behavior of ionic microgels in solution is sensitive to the distribution of fixed charge within the polymer-network gel and strongly depends on bulk concentrations of both microgels and salt ions.

On-Chip Fabrication of Colloidal Suprastructures by Assembly and Supramolecular Interlinking of Microgels.

In this report, a versatile method is demonstrated to create colloidal suprastructures by assembly and supramolecular interlinking of microgels using droplet-based microfluidics. The behavior of the microgels is systematically investigated to evaluate the influence of their concentration on their distribution between the continuous, the droplet phase, and the interface. At low concentrations, microgels are mainly localized at the water-oil interface whereas an excess of microgels results, following the complete coverage of the water-oil interface, in their distribution in the continuous phase. To stabilize the colloidal suprastructure, on-chip gelation is introduced by adding natural polyphenol tannic acid (TA) in the water phase. TA forms interparticle linking between the poly(N-vinylcaprolactam) (PVCL) microgels by supramolecular interactions. The combination of supramolecular interlinking with the variation of the microgel concentration in microfluidic droplets enables on-chip fabrication of defined colloidal suprastructures with morphologies ranging from colloidosomes to colloidal supraballs. The obtained supracolloidal structures exhibit a pH-responsive behavior with a disintegration at alkaline conditions within a scale of seconds. The destabilization process results from the deprotonation of phenolic groups and destruction of hydrogen bonds with PVCL chains at higher pH.

Rapeseed oil as the extraction solvent motivates fucoxanthin-loaded high internal phase emulsion preparation for food 3D printing

Fucoxanthin (FX), a non-provitamin A carotenoid pigment, is a well-known natural antioxidant contained in brown algae. The present study deals with an ultrasonic-assisted FX extraction process from Undaria pinnatifida with rapeseed oil as the solvent. Then, high internal phase emulsions (HIPEs) with the FX-rich rapeseed oil as the oil phase was constructed using a simple one-step method for food 3D printing. The FX-loaded HIPEs were stabilized by the gelatin (GE)-based microgel, which were prepared by GE complex coacervation with sodium alginate and transglutaminase cross-linking, for the improved delivery and stability of FX. FX-loaded HIPEs stabilized by 2 wt (wt)% GE-based microgel showed a small and uniform particle size and a stable microstructure. The HIPEs stabilized by 2 wt% GE-based microgel had the best FX stability (residual FX 84.81 ± 0.82%) and bioaccessibility (38.26 ± 1.21%). The excellent viscoelasticity, recovery rate and thixotropy of the HIPEs stabilized by 2 wt% GE-based microgel further confirmed the best 3D printing performance. Therefore, rapeseed oil as the extraction solvent motivates FX-loaded HIPEs preparation, and GE-based microgel concentration is crucial for 3D printing.

Emulsion-Templated Liquid Oil Structuring with Egg White Protein Microgel- Xanthan Gum.

In this study, oleogels were prepared by the emulsion-template method using egg-white protein microgel as a gelator and xanthan gum (XG) as thickener. The physicochemical properties of the emulsion and oleogels were investigated. The adsorption of protein on the surface of the oil droplet reached saturation when the protein microgel concentration reached 2%. The excess protein combined with XG and accumulated on the outer layer of the oleogel, which prevented the emulsion from flocculation, enhanced the oil-holding capacity of the oleogel, and had a positive effect on preventing the oxidation of oil. When the concentration of XG was less than 0.4%, the EWP microgel, combined with the XG, stabilized the emulsion. As the concentration of XG was greater than 0.4%, excessive XG in the emulsion improved the viscosity and mechanical properties of the emulsion to prevent the aggregation of oil droplets. However, the change in XG concentration had no significant effect on the oxidation of the oil.

Multi-material 3D Printing of Mechanochromic Double Network Hydrogels for On-Demand Patterning.

Cephalopods can change their color and patterns by activating the skin chromatophores for camouflage. However, in the man-made soft material systems, it is greatly challenging to fabricate the color-change structure in the desired patterns and shapes. Herein, we employ a multi-material microgel direct ink writing (DIW) printing method to make mechanochromic double network hydrogels in arbitrary shapes. We prepare the microparticles by grinding the freeze-dried polyelectrolyte hydrogel and immobilize the microparticles in the precursor solution to produce the printing ink. The polyelectrolyte microgels contain mechanophores as the cross-linkers. We adjust the rheological and printing properties of the microgel ink by tailoring the grinding time of freeze-dried hydrogels and microgel concentration. The multi-material DIW 3D printing technique is utilized to fabricate various 3D hydrogel structures which could change into a colorful pattern in response to applied force. The microgel printing strategy shows great potential in the fabrication of the mechanochromic device with arbitrary patterns and shapes.

How do the Local Physical, Biochemical, and Mechanical Properties of an Injectable Synthetic Anisotropic Hydrogel Affect Oriented Nerve Growth?

AbstractAs an injectable tissue regenerative platform, Anisogel aims to recapitulate the complex and anisotropic architecture of native extracellular matrix by the use of magneto‐responsive microgels, which are oriented under a low magnetic field of ≈100 mT, while a surrounding hydrogel matrix cross‐links around them. This system promotes the oriented growth of neurons when cultured in vitro. In this study, how the local microgel properties affect neurite outgrowth and orientation is aimed to understand using dorsal root ganglia from chicken embryos. When the surrounding matrix is a synthetic poly(ethylene glycol) hydrogel, the microgel concentration and length required to achieve oriented nerve growth is higher compared to fibrin‐based Anisogels. Microgels should be stiffer than the matrix for cells to sense the mechanical anisotropy but a wide range of microgel stiffness leads to similar cell alignment and growth. On the other hand, modification of the microgels with common extracellular matrix molecules enhances nerve growth but deteriorates nerve alignment compared to bioinert microgels in a cell adhesive surrounding gel. Finally, covalently coupling these microgels to the surrounding matrix reduces both cellular orientation and outgrowth suggesting a reduction in the ability of cells to sense the anisotropy.

Extraction of copper ions from aqueous medium by microgel particles for in-situ fabrication of copper nanoparticles to degrade toxic dyes

Abstract Most of the transition metal ions are toxic and their removal from water is important. For this purpose, nearly monodisperse spherical core shell microgel particles with diameter of 88 ± 3 nm have been synthesized by free radical precipitation polymerization method and characterized by fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Extraction of copper ions from water under several conditions of pH, copper ions content and core shell microgel concentrations was undertaken. Several adsorption isotherms were tested to explore the process of adsorption of copper ions on the microgel particles. Kinetics of adsorption process was examined by pseudo first order, pseudo second order, intra-particle diffusion and Elovich models. Copper ions adsorbed in shell region of core shell microgel were reduced to copper nanoparticles. The hybrid microgel was used to reduce organic pollutants such as 4-nitrophenol (4NP), methylene blue (MB), and methyl orange (MO) in aqueous medium. The value of pseudo first order rate constant for catalytic reduction of 4NP, MB, and MO was found 0.602, 0.831, and 0.874 min−1 respectively. The resultant core shell hybrid microgel system can serve as efficient catalyst for numerous other organic transformations.

Tuneable fluorescence and structural colour in PNIPAM microgel assemblies

The combination of fluorescence and structural colour in colloidal photonic glasses could be the starting point for the design of dynamic multiple responsive colloidal photonic materials for advanced applications in which the fluorescence intensity could be modulated by stimulus-induced colour changes. The merocyanine functionalization of the PNIPAM-based microgel system made it possible to obtain tuneable photonic colloidal glasses displaying vivid structural colours and fluorescence. For this purpose, the MC was introduced in some of the crosslinking points of the inner structure of a PNIPAM-based microgel system. These building blocks were left to organize in water (pH 4.5) to obtain photonic glasses. The structural colour was studied as a function of water concentration, so that increasing the microgel concentration led to a blue colour shift. The PBG was characterized by diffuse reflectance spectroscopy. Reflection imaging microscopy was used to understand the microstructure responsible for the PBG. It could be determined that the microgel particles decreased their diameter from 430 nm up to 220 nm to adjust to the glass organization. It has been found that MC fluorescence intensity in these assemblies depended on the photonic band gap (PBG) position in such manner, that strong quenching of MC fluorescence was observed when the PBG matched the MC excitation wavelength. Besides, the MC fluorescence excitation band was 10 nm shifted to higher wavelengths.

Does the Size of Microgels Influence the Toughness of Microgel-Reinforced Hydrogels?

Rapid advances in the biomedical field increasingly often demand soft materials that can be processed into complex 3D shapes while being able to reliably bear significant loads. Granular hydrogels have the potential to serve as artificial tissues because they can be 3D printed into complex shapes and their composition can be tuned over short length scales. Unfortunately, granular hydrogels are typically soft such that they cannot be used for load-bearing applications. To address this shortcoming, individual microgels can be connected through a percolating network, such that they introduce the double network toughening mechanism into granular hydrogels. However, the influence of the microgel size and concentration on the processing and toughness of microgel-reinforced hydrogels (MRHs) remains to be elucidated. Here, it is demonstrated that processing and toughness depend on the inter-microgel connectivity, while the stress at break is solely dependent on the microgel size. These findings offer an in-depth understanding of how liquid- and paste-like precursors containing soft, deformable microgels can be processed into bulk microstructured soft materials and how the size and concentration of these microgels influence the mechanical properties of microgel-reinforced hydrogels.

Structure-Activity-Relationship Studies to Elucidate Sources of Antibacterial Activity of Modular Polyacrylate Microgels.

Emerging infections of unknown origin and increasing bacterial resistance against available antibiotics necessitate the development of different antimicrobial agents with unconventional mechanisms of action. A promising strategy to meet this need may be found by combining polymeric scaffolds with transition metals, e.g., by decorating polyacrylate-based microgels with Cu(II) complexes. A series of structure-activity relationship studies using broth microdilution assays with such materials and Staphylococcus aureus concluded that the antimicrobial activity of microgels can be tailored during their synthesis by choice of co-monomers, by design of the binding strength between Cu(II) ions and backbone ligands, and by selection of the counter ions for coordination to the metal complexes. A microgel Cu2LP(EG) (L = VBbsdpo) with an optimized minimal inhibitory concentration of 0.39 ± 0.03 μg/mL is thereby derived and synthesized from 60 mol % of cross-linking ethylene glycol dimethacrylate, 40 mol % butyl acrylate, 0.5 mol % VBbsdpo ligand with 1 mol % Cu(II) ions, and 5 mol % ethylene glycol as counter ions. The antimicrobial activity of the microgel has a lifetime of over 18 months at ambient temperature. Bactericidal activity of the same microgel is observed by replating assays in less than 15 min when exposing S. aureus to microgel concentrations of 1.5-fold of its minimum inhibitory concentration (MIC) value or higher. Furthermore, spectrophotometric evaluations at 260 nm revealed time- and concentration-dependent release of intracellular bacterial components after interactions with the microgel indicating irreversible damage to the bacterial cell membrane as a possible mechanism of activity. Preliminary results indicate that the selected microgels are not cytotoxic toward human dermal fibroblasts at MIC value concentrations for over 20 h.

3D Printing of Microgel Scaffolds with Tunable Void Fraction to Promote Cell Infiltration.

Granular, microgel-based materials have garnered interest as promising tissue engineering scaffolds due to their inherent porosity, which can promote cell infiltration. Adapting these materials for 3D bioprinting, while maintaining sufficient void space to enable cell migration, can be challenging, since the rheological properties that determine printability are strongly influenced by microgel packing and void fraction. In this work, a strategy is proposed to decouple printability and void fraction by blending UV-crosslinkable gelatin methacryloyl (GelMA) microgels with sacrificial gelatin microgels to form composite inks. It is observed that inks with an apparent viscosity greater than ≈100 Pa s (corresponding to microgel concentrations ≥5 wt%) have rheological properties that enable extrusion-based printing of multilayered structures in air. By altering the ratio of GelMA to sacrificial gelatin microgels, while holding total concentration constant at 6 wt%, a family of GelMA:gelatin microgel inks is created that allows for tuning of void fraction from 0.20 to 0.57. Furthermore, human umbilical vein endothelial cells (HUVEC) seeded onto printed constructs are observed to migrate into granular inks in a void fraction-dependent manner. Thus, the family of microgel inks holds promise for use in 3D printing and tissue engineering applications that rely upon cell infiltration.

Tungsten disulfide (WS2) doped polyacrylamide (PAAm) composites: Gelation and optical studies

The organic Acrylamide (AAm) copolymerization in various contents of inorganic WS2 has been reported. The aim was to investigate the effect of the WS2 amount on the obtained morphology and the gelation process of the AAm composites. It was found that during gelation process the photon intensity of transmission decreased significantly above some critical time, called the gel point, tg. The decrease in the photon intensity of transmission was related to the increase in the intensity of scattered light from the gel attributable to the production of microgel that occurs while copolymerization held in AAm with Bis-Acrylamide (BIS). Gel points were found to be increased by increasing WS2 content. Time-dependent scattering of composites manifests the growth mechanism, the greater microgel particles, as in agreement with Rayleigh’s equation of scattering. It is determined that concentration of microgels is inversely proportional to the WS2 content. The composite rate constants of gelation, kr were produced and observed that it is proportional to WS2 content. It is understood that inclusion of WS2 in AAm system during gelation delays the process at early times but then contributes to increase the gelation process by increasing the rate of polymerization. Besides less compact PAAm gels are produced in the presence of WS2 atoms. It is also shown that the microgel growth mechanism and gel point of PAAm composite incorporated with WS2 can be significantly tailored by the amount of WS2. Tunable growth mechanism and critical gelation point is crucial for flexible electronic applications.

Morphology-controllable amphiphilic cellulose microgels made from self-assembly of hydrophobic long-chain bromide-alkylated-cellulose/gelatin copolymer

A cellulose-based microgel is firstly synthesized via chemically coupling gelatin and cellulose, and then amphiphilic cellulose copolymers (HMGC) are prepared by alkylated cellulose-based microgel from different long-chain alkyl groups. The long-chain alkyl group is mainly bonded onto the residual hydroxyl group at C6 from the AGU of cellulose and the imino groups of gelatin, respectively. The results of self-assembly behavior of HMGC demonstrate that the critical aggregation concentrations of the microgels are in the range from 0.628 to 0.075 mg/mL, and the corresponding hydrodynamic diameters are between 104–1000 nm. Besides, the HMGC can self-assemble into microgels of various morphologies including cotton flocculence, sphere, rod-like, vesicle, flower-like cluster, snowflake-like, urchin-like, and coral shapes. These novel morphologies can be controlled by adjusting the degree of alkylation, the length of the alkyl chain, and the concentration of microgel. Furthermore, the possible formation mechanism of the multiform microgels is proposed from the chain conformation.