Gels — Open Access Journal

In this work, we report the design and fabrication of a dual-function integrated system to monitor, in real time, the release of previously loaded 2-methyl-1,4-naphthoquinone (MeNQ), also named vitamin K3. The newly developed system consists of poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, which were embedded into a poly-γ-glutamic acid (γ-PGA) biohydrogel during the gelling reaction between the biopolymer chains and the cross-linker, cystamine. After this, agglomerates of PEDOT nanoparticles homogeneously dispersed inside the biohydrogel were used as polymerization nuclei for the in situ anodic synthesis of poly(hydroxymethyl-3,4-ethylenedioxythiophene) in aqueous solution. After characterization of the resulting flexible electrode composites, their ability to load and release MeNQ was proven and monitored. Specifically, loaded MeNQ molecules, which organized in shells around PEDOT nanoparticles agglomerates when the drug was simply added to the initial gelling solution, were progressively released to a physiological medium. The latter process was successfully monitored using an electrode composite through differential pulse voltammetry. The fabrication of electroactive flexible biohydrogels for real-time release monitoring opens new opportunities for theranostic therapeutic approaches. Full article

Bioprinting techniques allow for the recreation of 3D tissue-like structures. By deposition of hydrogels combined with cells (bioinks) in a spatially controlled way, one can create complex and multiscale structures. Despite this promise, the ability to deposit customizable cell-laden structures for soft tissues is still limited. Traditionally, bioprinting relies on hydrogels comprised of covalent or mostly static crosslinks. Yet, soft tissues and the extracellular matrix (ECM) possess viscoelastic properties, which can be more appropriately mimicked with hydrogels containing reversible crosslinks. In this study, we have investigated aldehyde containing oxidized alginate (ox-alg), combined with different cross-linkers, to develop a small library of viscoelastic, self-healing, and bioprintable hydrogels. By using distinctly different imine-type dynamic covalent chemistries (DCvC), (oxime, semicarbazone, and hydrazone), rational tuning of rheological and mechanical properties was possible. While all materials showed biocompatibility, we observed that the nature of imine type crosslink had a marked influence on hydrogel stiffness, viscoelasticity, self-healing, cell morphology, and printability. The semicarbazone and hydrazone crosslinks were found to be viscoelastic, self-healing, and printable—without the need for additional Ca²⁺ crosslinking—while also promoting the adhesion and spreading of fibroblasts. In contrast, the oxime cross-linked gels were found to be mostly elastic and showed neither self-healing, suitable printability, nor fibroblast spreading. The semicarbazone and hydrazone gels hold great potential as dynamic 3D cell culture systems, for therapeutics and cell delivery, and a newer generation of smart bioinks. Full article

There is a strong commercial need for inexpensive point-of-use sensors for monitoring disease biomarkers or environmental contaminants in drinking water. Point-of-use sensors that employ smart polymer hydrogels as recognition elements can be tailored to detect almost any target analyte, but often suffer from long response times. Hence, we describe here a fabrication process that can be used to manufacture low-cost point-of-use hydrogel-based microfluidics sensors with short response times. In this process, mask-templated UV photopolymerization is used to produce arrays of smart hydrogel pillars inside sub-millimeter channels located upon microfluidics devices. When these pillars contact aqueous solutions containing a target analyte, they swell or shrink, thereby changing the resistance of the microfluidic channel to ionic current flow when a small bias voltage is applied to the system. Hence resistance measurements can be used to transduce hydrogel swelling changes into electrical signals. The only instrumentation required is a simple portable potentiostat that can be operated using a smartphone or a laptop, thus making the system suitable for point of use. Rapid hydrogel response rate is achieved by fabricating arrays of smart hydrogels that have large surface area-to-volume ratios. Full article

Organic polymer-hydrogels are known to be capable of directing the nucleation and growth of inorganic materials, such as silica, metal oxides, apatite or metal chalcogenides. This approach can be exploited in the synthesis of materials that exhibit defined nanoporosity. When the organic polymer-based hydrogel is incorporated in the inorganic product, a composite is formed from which the organic component may be selectively removed, yielding nanopores in the inorganic product. Such porogenic impact resembles the concept of using soft or hard templates for porous materials. This micro-review provides a survey of select examples from the literature. Full article

In this study, we evaluate hydrogels based on oxidized hyaluronic acid, cross-linked with adipic acid dihydrazide, for their suitability as bioinks for 3D bioprinting. Aldehyde containing hyaluronic acid (AHA) is synthesized and cross-linked via Schiff Base chemistry with bifunctional adipic acid dihydrazide (ADH) to form a mechanically stable hydrogel with good printability. Mechanical and rheological properties of the printed and casted hydrogels are tunable depending on the concentrations of AHA and ADH cross-linkers. Full article

Urea (URE) and guanidine hydrochloride (GHC) possessing strong chaotropic properties in aqueous media were added to DMSO solutions of poly(vinyl alcohol) (PVA) to be gelled via freeze–thaw processing. Unexpectedly, it turned out that in the case of the PVA cryotropic gel formation in DMSO medium, the URE and GHC additives caused the opposite effects to those observed in water, i.e., the formation of the PVA cryogels (PVACGs) was strengthened rather than inhibited. Our studies of this phenomenon showed that such “kosmotropic-like” effects were more pronounced for the PVACGs that were formed in DMSO in the presence of URE additives, with the effects being concentration-dependent. The additives also caused significant changes in the macroporous morphology of the cryogels; the commonly observed trend was a decrease in the structural regularity of the additive-containing samples compared to the additive-free gel sample. The viscosity measurements revealed consistent changes in the intrinsic viscosity, Huggins constant, and the excess activation heat of the viscosity caused by the additives. The results obtained evidently point to the urea-induced decrease in the solvation ability of DMSO with respect to PVA. As a result, this effect can be the key factor that is responsible for strengthening the structure formation upon the freeze–thaw gelation of this polymer in DMSO additionally containing additives such as urea, which is capable of competing with PVA for the solvent. Full article

Disulfides are used extensively in reversible cross-linking because of the ease of reduction into click-reactive thiols. However, the free-radical scavenging properties upon reduction are often under-considered. The free thiols produced upon reduction of this disulfide material mimic the cellular reducing chemistry (glutathione) that serves as a buffer against acute oxidative stress. A nanoparticle formulation producing biologically relevant concentrations of thiols may not only provide ample chemical conjugation sites, but potentially be useful against severe acute oxidative stress exposure, such as in targeted radioprotection. In this work, we describe the synthesis and characterization of highly thiolated poly (β-amino ester) (PBAE) nanoparticles formed from the reduction of bulk disulfide cross-linked PBAE hydrogels. Degradation-tunable PBAE hydrogels were initially synthesized containing up to 26 wt % cystamine, which were reduced into soluble thiolated oligomers and formulated into nanoparticles upon single emulsion. These thiolated nanoparticles were size-stable in phosphate buffered saline consisting of up to 11.0 ± 1.1 mM (3.7 ± 0.3 mmol thiol/g, n = 3 M ± SD), which is an antioxidant concentration within the order of magnitude of cellular glutathione (1–10 mM). Full article

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