Gels, Volume 4, Issue 3 (September 2018) – 24 articles

Emulsions can be prepared from protein microgel particles as an alternative to traditional emulsifiers. Prior experiments have indicated that smaller and more deformable microgels would decrease both the physical destabilization of emulsions and the diffusion-based losses of entrapped volatile molecules. The microgels were prepared from β-lactoglobulin with an average diameter of 150 nm, 231 nm, or 266 nm; large microgels were cross-linked to decrease their deformability. Dilute emulsions of 15–50 μm diameter were prepared with microgels by high shear mixing. Light scattering and microscopy showed that the emulsions prepared with larger, untreated microgels possessed a larger initial droplet size, but were resistant to droplet growth during storage or after acidification, increased ionic strength, and exposure to surfactants. The emulsions prepared with cross-linked microgels emulsions were the least resistant to flocculation, creaming, and shrinkage. All emulsion droplets shrank as limonene was lost during storage, and the inability of microgels to desorb caused droplets to become non-spherical. The microgels were not displaced by Tween 20 but were displaced by excess sodium dodecyl sulfate. Hexanol diffusion and associated shrinkage of pendant droplets was not prevented by any of the microgels, yet the rate of shrinkage was reduced with the largest microgels. Full article

Gelled lyotropic liquid crystals can be formed by adding a gelator to a mixture of surfactant and solvent. If the gel network and the liquid-crystalline phase coexist without influencing each other, the self-assembly is called orthogonal. In this study, the influence of the organogelator 12-hydroxyoctadecanoic acid (12-HOA) on the lamellar and hexagonal liquid crystalline phases of the binary system H₂O–C₁₂E₇ (heptaethylene glycol monododecyl ether) is investigated. More precisely, we added 12-HOA at mass fractions from 0.015 to 0.05 and studied the resulting phase diagram of the system H₂O–C₁₂E₇ by visual observation of birefringence and by ²H NMR spectroscopy. In addition, the dynamic shear moduli of the samples were measured in order to examine their gel character. The results show that 12-HOA is partly acting as co-surfactant, manifested by the destabilization of the hexagonal phase and the stabilization of the lamellar phase. The higher the total surfactant concentration, the more 12-HOA is incorporated in the surfactant layer. Accordingly, its gelation capacity is substantially reduced in the surfactant solution compared to the system 12-HOA–n-decane, and large amounts of gelator are required for gels to form, especially in the lamellar phase. Full article

A variety of cryogenically-structured polymeric materials are of significant scientific and applied interest in various areas. However, in spite of considerable attention to these materials and intensive elaboration of their new examples, as well as the impressive growth in the number of the publications and patents on this topic over the past two decades, a marked variability of the used terminology and definitions is frequently met with in the papers, reviews, theses, patents, conference presentations, advertising materials and so forth. Therefore, the aim of this brief communication is to specify the basic terms and definitions in the particular field of macromolecular science. Full article

Gastric mucus gel is known to exhibit dramatic and unique swelling behaviors in response to the ionic composition of the hydrating solution. This swelling behavior is important in the maintenance of the mucus layer lining the stomach wall, as the layer is constantly digested by enzymes in the lumen, and must be replenished by new mucus that swells as it is secreted from the gastric wall. One hypothesis suggests that the condensed state of mucus at secretion is maintained by transient bonds with calcium that form crosslinks. These crosslinks are lost as monovalent cations from the environment displace divalent crosslinkers, leading to a dramatic change in the energy of the gel and inducing the swelling behavior. Previous modeling work has characterized the equilibrium behavior of polyelectrolyte gels that respond to calcium crosslinking. Here, we present an investigation of the dynamic swelling behavior of a polyelectrolytic gel model of mucus. In particular, we quantified the rate at which a globule of initially crosslinked gel swells when exposed to an ionic bath. The dependence of this swelling rate on several parameters was characterized. We observed that swelling rate has a non-monotone dependence on the molarity of the bath solution, with moderate concentrations of available sodium inducing the fastest swelling. Full article

The ongoing progress in the development of hydrogel technology has led to the emergence of materials with unique features and applications in medicine. The innovations behind the invention of nanocomposite hydrogels include new approaches towards synthesizing and modifying the hydrogels using diverse nanofillers synergistically with conventional polymeric hydrogel matrices. The present review focuses on the unique features of various important nanofillers used to develop nanocomposite hydrogels and the ongoing development of newly hydrogel systems designed using these nanofillers. This article gives an insight in the advancement of nanocomposite hydrogels for nanomedicine. Full article

Biodegradable poly(ethylene glycol)-block-poly(-lactic acid) (PEG-b-PLA) nanoparticles (NPs) were prepared by nanoprecipitation with controlled dimension and with different electric charges, as monitored by dynamic light scattering (DLS). Then NPs were loaded within hydrogels (HG) developed for biomedical applications in the central nervous system, with different pore sizes (30 and 90 nm). The characteristics of the resulting composite hydrogel-NPs system were firstly studied in terms of ability to control the release of small steric hindrance drug mimetic. Then, diffusion-controlled release of different charged NPs from different entangled hydrogels was studied in vitro and correlated with NPs electric charges and hydrogel mean mesh size. These studies showed different trends, that depend on NPs superficial charge and HG mesh size. Release experiments and diffusion studies, then rationalized by mathematical modeling, allowed us to build different drug delivery devices that can satisfy different medical needs. Full article

3D bioprinting holds great promise in the field of regenerative medicine as it can create complex structures in a layer-by-layer manner using cell-laden bioinks, making it possible to imitate native tissues. Current bioinks lack both high printability and biocompatibility required in this respect. Hence, the development of bioinks that exhibit both properties is needed. In our previous study, a furfuryl-gelatin-based bioink, crosslinkable by visible light, was used for creating mouse mesenchymal stem cell-laden structures with a high fidelity. In this study, lattice mesh geometries were printed in a comparative study to test against the properties of a traditional rectangular-sheet. After 3D printing and crosslinking, both structures were analysed for swelling and rheological properties, and their porosity was estimated using scanning electron microscopy. The results showed that the lattice structure was relatively more porous with enhanced rheological properties and exhibited a lower degradation rate compared to the rectangular-sheet. Further, the lattice allowed cells to proliferate to a greater extent compared to the rectangular-sheet, which initially retained a lower number of cells. All of these results collectively affirmed that the lattice poses as a superior scaffold design for tissue engineering applications. Full article

Hydrogels are three-dimensional networks composed of hydrated polymer chains and have been a material of choice for many biomedical applications such as drug delivery, biosensing, and tissue engineering due to their unique biocompatibility, tunable physical characteristics, flexible methods of synthesis, and range of constituents. In many cases, methods for crosslinking polymer precursors to form hydrogels would benefit from being highly selective in order to avoid cross-reactivity with components of biological systems leading to adverse effects. Crosslinking reactions involving the thiol group (SH) offer unique opportunities to construct hydrogel materials of diverse properties under mild conditions. This article reviews and comments on thiol-mediated chemoselective and biocompatible strategies for crosslinking natural and synthetic macromolecules to form injectable hydrogels for applications in drug delivery and cell encapsulation. Full article

Our recent studies have shown that the hydrogels prepared by blending clay, a dispersant of clay, and a polyelectrolyte (sodium polyacrylate (PAAS)) possess excellent mechanical properties. In order to clarify the mechanism of the toughness, we have so far investigated the effects of the composition, molecular mass of the polymer, and kinds of polymers on the mechanical properties. This study has focused upon the mechanical properties and structures of the clay/PAAS gels using three kinds of smectite clay minerals such as synthetic hectorite (laponite XLG), saponite (sumecton-SA), montmorillonite (kunipia-F), whose particle size becomes larger according to the sequence. Laponite/PAAS and sumecton/PAAS gels were quite tough for high compression, whereas kunipia-F/PAAS did not gelate. In comparison between sumecton/PAAS gel and laponite/PAAS gel, the mechanical property of the former gel was poorer than that of the latter gel due to the inhomogeneous distribution of clay platelets in the gel. Synchrotron small-angle X-ray scattering experiments revealed that their clay platelets laid down in the stretching direction under elongation. Furthermore, it was found that sumecton/PAAS gel under elongation was arranged with an interparticle distance of ~6.3 nm in the direction perpendicular to the stretching. Such local ordering under elongation may originate in local aggregation of sumecton platelets in the original state without elongation. Full article

The behavior of poly(sodium acrylate-co-acrylamide) copolymer hydrogels with varied chemical compositions in artificial pore solutions with three different pH values is examined. The absorption, chemical characteristics, mechanical stiffness, and desorption of the hydrogels in contact with a porous cementitious material were investigated. It was observed that the surface characteristics of the hydrogels play an important role in the desorption of hydrogels due to the capillary forces. It was shown that in the hydrogel systems studied here, the bonding between the hydrogels and the porous cementitious material is improved with an increase in the content of acrylamide in the hydrogels, and this results in an increased desorption rate of the hydrogels. Full article

Hydrogels are an interesting class of materials used in extrusion-based 3D printing, e.g., for drug delivery or tissue engineering. However, new hydrogel formulations for 3D printing as well as a detailed understanding of crucial formulation properties for 3D printing are needed. In this contribution, hydrogels based on poly(ethylene glycol) diacrylate (PEG-DA) and the charged monomers 3-sulfopropyl acrylate and [2-(acryloyloxy)ethyl]trimethylammonium chloride are formulated for 3D printing, together with Poloxamer 407 (P407). Chemical curing of formulations with PEG-DA and up to 5% (w/w) of the charged monomers was possible without difficulty. Through careful examination of the rheological properties of the non-cured formulations, it was found that flow properties of formulations with a high P407 concentration of 22.5% (w/w) possessed yield stresses well above 100 Pa together with pronounced shear thinning behavior. Thus, those formulations could be processed by 3D printing, as demonstrated by the generation of pyramidal objects. Modelling of the flow profile during 3D printing suggests that a plug-like laminar flow is prevalent inside the printer capillary. Under such circumstances, fast recovery of a high vicosity after material deposition might not be necessary to guarantee shape fidelity because the majority of the 3D printed volume does not face any relevant shear stress during printing. Full article

3D plotting is an additive manufacturing technology enabling biofabrication, thus the integration of cells or biologically sensitive proteins or growth factors into the manufacturing process. However, most (bio-)inks developed for 3D plotting were not shown to be processed into clinically relevant geometries comprising critical overhangs and cavities, which would collapse without a sufficient support material. Herein, we have developed a support hydrogel ink based on methylcellulose (mc), which is able to act as support as long as the co-plotted main structure is not stable. Therefore, 6 w/v %, 8 w/v % and 10 w/v % mc were allowed to swell in water, resulting in viscous inks, which were characterized for their rheological and extrusion properties. The successful usage of 10 w/v % mc as support ink was proven by multichannel plotting of the support together with a plottable calcium phosphate cement (CPC) acting as main structure. CPC scaffolds displaying critical overhangs or a large central cavity could be plotted accurately with the newly developed mc support ink. The dissolution properties of mc allowed complete removal of the gel without residuals, once CPC setting was finished. Finally, we fabricated a scaphoid bone model by computed tomography data acquisition and co-extrusion of CPC and the mc support hydrogel. Full article

Chitosan macro- and micro/nano-gels have gained increasing attention in recent years, especially in the biomedical field, given the well-documented low toxicity, degradability, and non-immunogenicity of this unique biopolymer. In this review we aim at recapitulating the recent gelling concepts for developing chitosan-based physical gels. Specifically, we describe how nowadays it is relatively simple to prepare networks endowed with different sizes and shapes simply by exploiting physical interactions, namely (i) hydrophobic effects and hydrogen bonds—mostly governed by chitosan chemical composition—and (ii) electrostatic interactions, mainly ensured by physical/chemical chitosan features, such as the degree of acetylation and molecular weight, and external parameters, such as pH and ionic strength. Particular emphasis is dedicated to potential applications of this set of materials, especially in tissue engineering and drug delivery sectors. Lastly, we report on chitosan derivatives and their ability to form gels. Additionally, we discuss the recent findings on a lactose-modified chitosan named Chitlac, which has proved to form attractive gels both at the macro- and at the nano-scale. Full article

We report the room temperature synthesis of spherical millimeter-size polyurea (PUA) aerogel beads. Wet-gels of said beads were obtained by dripping a propylene carbonate solution of an aliphatic triisocyanate based on isocyanurate nodes into a mixture of ethylenediamine and heavy mineral oil. Drying the resulting wet spherical gels with supercritical fluid (SCF) CO₂ afforded spherical aerogel beads with a mean diameter of 2.7 mm, and a narrow size distribution (full width at half maximum: 0.4 mm). Spherical PUA aerogel beads had low density (0.166 ± 0.001 g cm^–3), high porosity (87% v/v) and high surface area (197 m² g^–1). IR, ¹H magic angle spinning (MAS) and ¹³C cross-polarization magic angle spinning (CPMAS) NMR showed the characteristic peaks of urea and the isocyanurate ring. Scanning electron microscopy (SEM) showed the presence of a thin, yet porous skin on the surface of the beads with a different (denser) morphology than their interior. The synthetic method shown here is simple, cost-efficient and suitable for large-scale production of PUA aerogel beads. Full article

Cancer research has traditionally relied on two-dimensional (2D) cell culture, focusing mainly on cancer cells and their abnormal genetics. However, over the past decade, tumors have been accepted as complex tissues rather than a homogenous mass of proliferating cells. Consequently, cancer cells’ behavior can only be deciphered considering the contribution of the cells existing in the tumor stroma as well as its complex microenvironment. Since the tumor microenvironment plays a critical role in tumorigenesis, it is widely accepted that culturing cells in three-dimensional (3D) scaffolds, which mimic the extracellular matrix, represents a more realistic scenario. In the present work, an in vitro 3D co-culture system based on the self-assembling peptide scaffold RAD16-I (SAPS RAD16-I) was developed as a cancer model. For that, PANC-1 cells were injected into a RAD16-I peptide scaffold containing fibroblasts, resulting in a 3D system where cancer cells were localized in a defined area within a stromal cells matrix. With this system, we were able to study the effect of three well-known pharmaceutical drugs (Gemcitabine, 5-Fluorouracil (5-FU), and 4-Methylumbelliferone (4-MU)) in a 3D context in terms of cell proliferation and survival. Moreover, we have demonstrated that the anti-cancer effect of the tested compounds can be qualitatively and quantitatively evaluated on the developed 3D co-culture system. Experimental results showed that Gemcitabine and 5-FU prevented PANC-1 cell proliferation but had a high cytotoxic effect on fibroblasts as well. 4-MU had a subtle effect on PANC-1 cells but caused high cell death on fibroblasts. Full article

Modified biomaterials have for years been the focus of research into establishing new bone substitutes. In our preceding in vitro study employing different cell cultures, we developed chemically and mechanically characterized hydrogels based on photocrosslinkable dextran derivatives and demonstrated their cytocompatibility and their beneficial effects on the proliferation of osteoblasts and endothelial cells. In the present in vivo study, we investigate photocrosslinked dextran-based hydrogels in critical size defects in mice to evaluate their potential as carrier systems for cells or for a specific angiogenesis enhancing cytokine to induce bone formation. We could demonstrate that, with optimized laboratory practice, the endotoxin content of hydrogels could be reduced below the Food and Drug Administration (FDA)-limit. Dextran-based hydrogels were either loaded with a monoculture of endothelial cells or a co-culture of human osteoblasts with endothelial cells, or with stromal-derived-growth factor (SDF-1). Scaffolds were implanted into a calvarial defect of critical size in mice and their impact on bone formation was assessed by µCt-analyses, histology and immunohistology. Our study demonstrates that promotion of angiogenesis either by SDF-1 or a monoculture of endothelial cells induces bone regeneration at a physiological level. These in vivo results indicate the potential of dextran-based hydrogel composites in bone regeneration to deliver cells and cytokines to the defect site. Full article

Chemotherapy is commonly associated with limited effectiveness and unwanted side effects in normal cells and tissues, due to the lack of specificity of therapeutic agents to cancer cells when systemically administered. In brain tumors, the existence of both physiological barriers that protect tumor cells and complex resistance mechanisms to anticancer drugs are additional obstacles that hamper a successful course of chemotherapy, thus resulting in high treatment failure rates. Several potential surrogate therapies have been developed so far. In this context, hydrogel-based systems incorporating nanostructured drug delivery systems (DDS) and hydrogel nanoparticles, also denoted nanogels, have arisen as a more effective and safer strategy than conventional chemotherapeutic regimens. The former, as a local delivery approach, have the ability to confine the release of anticancer drugs near tumor cells over a long period of time, without compromising healthy cells and tissues. Yet, the latter may be systemically administered and provide both loading and targeting properties in their own framework, thus identifying and efficiently killing tumor cells. Overall, this review focuses on the application of hydrogel matrices containing nanostructured DDS and hydrogel nanoparticles as potential and promising strategies for the treatment and diagnosis of glioblastoma and other types of brain cancer. Some aspects pertaining to computational studies are finally addressed. Full article

Hydrogels are materials specially suited for encapsulation of biological elements. Their large water content provides an environment compatible with most biological molecules. Their crosslinked nature also provides an ideal material for the protection of encapsulated biological elements against degradation and/or immune recognition. This makes them attractive not only for controlled drug delivery of proteins, but they can also be used to encapsulate cells that can have therapeutic applications. Thus, hydrogels can be used to create systems that will deliver required therapies in a controlled manner by either encapsulation of proteins or even cells that produce molecules that will be released from these systems. Here, an overview of hydrogel encapsulation strategies of biological elements ranging from molecules to cells is discussed, with special emphasis on therapeutic applications. Full article

We present a scaling model based on a moving boundary picture to describe heterogeneous gelation dynamics. The dynamics of gelation induced by different gelation mechanisms is expressed by the scaled equation for the time taken for development of the gel layer with a few kinetic coefficients characterizing the system. The physical meaning obtained by the analysis for a simple boundary condition from the standpoint of the phase transition shows that the time development of the gelation layer depends on whether the dynamics of the order parameter expressing the gelation of the polymer solution is fast or slow compared with the diffusion of the gelators in the heterogeneous gelation. The analytical method is used to understand the coagulation of blood from various animals. An experiment using systems with plasma coagulation occurring at interfaces with calcium chloride solution and with packed erythrocytes is performed to provide the data for model fitting and it is clarified that a few key kinetic coefficients in plasma coagulation can be estimated from the analysis of gelation dynamics. Full article

The gelation and structural formation of two types of amylose in alkaline solution by in situ neutralization was monitored with time-resolved small-angle X-ray scattering (tr-SAXS). Sharp increases of SAXS profile in lower angle region were observed after gelation. The results showed that aggregation of amylose chains led to a gel point with crystal growth. The aggregation appeared to function as a junction zone, and the aggregate structure depended on the molecular weight of amylose. A high-molecular-weight sample was fitted using a Debye-Bueche function, and a low-molecular-weight sample was fitted using a stretched exponential function. Full article

Dynamics of solvent molecules restricted in poly (acryl amide) gels immersed in solvent mixtures of acetone–, 1,4-dioxane–, and dimethyl sulfoxide–water were analyzed by the time domain reflectometry method of dielectric spectroscopy and the pulse field gradient method of nuclear magnetic resonance. Restrictions of dynamic behaviors of solvent molecules were evaluated from relaxation parameters such as the relaxation time, its distribution parameter, and the relaxation strength obtained by dielectric measurements, and similar behaviors with polymer concentration dependences for the solutions were obtained except for the high polymer concentration in collapsed gels. Scaling analyses for the relaxation time and diffusion coefficient respectively normalized by those for bulk solvent suggested that the scaling exponent determined from the scaling variable defined as a ratio of the size of solvent molecule to mesh size of polymer networks were three and unity, respectively, except for collapsed gels. The difference in these components reflects characteristic molecular interactions in the rotational and translational diffusions, and offered a physical picture of the restriction of solvent dynamics. A universal treatment of slow dynamics due to the restriction from polymer chains suggests a new methodology of characterization of water structures. Full article