Gels — Open Access Journal

Background: The new concepts of personalized and precision medicine require the design of more and more refined delivery systems. In this frame, hydrogels can play a very important role as they represent the best surrogate of soft living tissues for what concerns rheological properties. Thus, this paper focusses on a global theoretical approach able to describe how hydrogel polymeric networks can affect the release kinetics of drugs characterized by different sizes. The attention is focused on a case study dealing with an interpenetrated hydrogel made up by alginate and poly(N-vinyl-2-pyrrolidone). Methods: Information about polymeric network characteristics (mesh size distribution and polymer volume fraction) is deduced from the theoretical interpretation of the rheological and the low field Nuclear Magnetic Resonance (NMR) characterization of hydrogels. This information is then, embodied in the mass balance equation whose resolution provides the release kinetics. Results: Our simulations indicate the influence of network characteristics on release kinetics. In addition, the reliability of the proposed approach is supported by the comparison of the model outcome with experimental release data. Conclusions: This study underlines the necessity of a global theoretical approach in order to design reliable delivery systems based on hydrogels. Full article

Honey is well-known for its wound healing capability and Manuka honey (MH) contains a unique Manuka factor, providing an additional antibacterial agent. Previously, there has not been a practical way to apply MH to a wound site, which renders treatment for an extended period extremely difficult. Tissue-engineered scaffolds offer an alternative treatment method to standard dressings by providing varying geometries to best treat the specific tissue. MH was incorporated into cryogels, hydrogels, and electrospun scaffolds to assess the effect of scaffold geometry on bacterial clearance and adhesion, as well as cellular adhesion. Electrospun scaffolds exhibited a faster release due to the nanoporous fibrous geometry which led to a larger partial bacterial clearance as compared to the more three-dimensional cryogels (CG) and hydrogels (HG). Similarly, the fast release of MH from the electrospun scaffolds resulted in reduced bacterial adhesion. Overall, the fast MH release of the electrospun scaffolds versus the extended release of the HG and CG scaffolds provides differences in cellular/bacterial adhesion and advantages for both short and long-term applications, respectively. This manuscript provides a comparison of the scaffold pore structures as well as bacterial and cellular properties, providing information regarding the relationship between varying scaffold geometry and MH efficacy. Full article

Supermacroporous gels, called cryogels, are unique scaffolds that can be prepared by polymerization of monomer solution under sub-zero temperatures. They are widely used in many applications and have significant potential biomaterials, especially for biomedical applications due to their inherent interconnected supermacroporous structures and easy formation of composite polymers in comparison to other porous polymer synthesis techniques. This review highlights the fundamentals of supermacroporous cryogels and composite cryogels, and then comprehensively summarizes recent studies in preparation, functionalization, and utilization with mechanical, biological and physicochemical features, according to the biomedical applications. Furthermore, conclusions and outlooks are discussed for the use of these promising and durable supermacroporous composite cryogels. Full article

Chia (Salvia hispanica L.) is an oilseed plant which contains proteins of high biological value and other healthy components with interesting technological properties. For these reasons, chia could be a promising option for the formation and stabilization of oil-in-water emulsions. The aim of this study is to evaluate the potential of chia protein (from chia flour) in the formation of emulsions. To that end, composition and technological and structural properties determined by infrared spectroscopy were investigated in conventional (EC) and gelled (EGC) emulsions with chia and compared with their corresponding soy protein emulsions with the same protein content [conventional (ES) or gelled (EGS)] used as reference. All emulsions containing chia had better fat and water binding properties than those elaborated with soy protein isolate (SPI). The color of the emulsions varied significantly depending on whether the emulsions were made with chia or SPI. EGS and EGC exhibited the greatest (p < 0.05) penetration force values, being EGC the firmest (p < 0.05). Depending on the type of emulsion, Attenuated Total Reflectance (ATR)-FTIR Spectroscopy revealed differences in their lipid structure and interaction in terms of lipid acyl chain mobility (order/disorder) and emulsion droplet size. These structural characteristics could be related to the textural behavior of emulsions. Full article

Recent progress in the development of gels showing triplet-triplet annihilation based photon upconversion (TTA-UC) is reviewed. Among the two families of upconverting gels reported, those display TTA-UC based on molecular diffusion show performances comparable to those in solutions, and the TTA-UC therein are affected by dissolved molecular oxygen. Meanwhile, air-stable TTA-UC is achieved in organogels and hydrogels by suitably accumulating TTA-UC chromophores which are stabilized by hydrogen bonding networks of the gelators. The unique feature of the air-stable upconverting gels is that the self-assembled nanostructures are protected from molecular oxygen dissolved in the microscopically interconnected solution phase. The presence of the bicontinuous structures formed by the upconverting fibrous nanoassemblies and the solution phase is utilized to design photochemical reaction systems induced by TTA-UC. Future challenges include in vivo applications of hydrogels showing near infrared-to-visible TTA-UC. Full article

Hydrogels with spatiotemporally tunable mechanical properties have been increasingly employed for studying the impact of tissue mechanics on cell fate processes. These dynamic hydrogels are particularly suitable for recapitulating the temporal stiffening of a tumor microenvironment. To this end, we have reported an enzyme-mediated stiffening hydrogel system where tyrosinase (Tyr_ase) was used to stiffen orthogonally crosslinked cell-laden hydrogels. Herein, a mathematical model was proposed to describe enzyme diffusion and reaction within a highly swollen gel network, and to elucidate the critical factors affecting the degree of gel stiffening. Briefly, Fick’s second law of diffusion was used to predict enzyme diffusion in a swollen poly(ethylene glycol) (PEG)-peptide hydrogel, whereas the Michaelis–Menten model was employed for estimating the extent of enzyme-mediated secondary crosslinking. To experimentally validate model predictions, we designed a hydrogel system composed of 8-arm PEG-norbornene (PEG8NB) and bis-cysteine containing peptide crosslinker. Hydrogel was crosslinked in a channel slide that permitted one-dimensional diffusion of Tyr_ase. Model predictions and experimental results suggested that an increasing network crosslinking during stiffening process did not significantly affect enzyme diffusion. Rather, diffusion path length and the time of enzyme incubation were more critical in determining the distribution of Tyr_ase and the formation of additional crosslinks in the hydrogel network. Finally, we demonstrated that the enzyme-stiffened hydrogels exhibited elastic properties similar to other chemically crosslinked hydrogels. This study provides a better mechanistic understanding regarding the process of enzyme-mediated dynamic stiffening of hydrogels. Full article

In this study, the effect of a composition (protein to fat (P/F) ratio) and a processing condition (homogenization pressure for emulsification of cheese milk) on the texture, microstructure, and bioaccessibility of vitamin D₃ of a model acid coagulated fresh cheese was evaluated. It was hypothesized that increasing P/F ratios (0.9, 1.3, 1.7, and 2) and homogenization pressures (17, 50, 75, and 150 MPa) will decrease the particle size of the cheese milk emulsion. The decreased emulsion particle size will result in a more rigid and elastic cheese matrix with smaller pore sizes, with an increased interfacial surface area of fat particles, which will then improve the bioaccessibility of vitamin D₃. The P/F ratio exhibited a positive impact on the texture in a large deformation analysis. On the other hand, the effect of the P/F ratio and homogenization pressure was not significant on rheological properties of the cheese using a small deformation by means of a frequency sweep test, nor the porosity determined by environmental scanning electron microscopy (ESEM). These results suggested that the modification of the microstructure of acid coagulated fresh cheeses required other variables than P/F ratio and homogenization pressure probably due to a compression step after curd formation. Interestingly, the bioaccessibility of vitamin D₃ measured by in vitro digestion was reduced as P/F ratio and homogenization pressure increased, which may indicate a reinforced protein–protein interaction that affected protein hydrolysis. Full article

This article is a personal account of the author, who serendipitously entered the field of supramolecular gels nearly two decades ago. A supramolecular synthon approach in the context of crystal engineering was utilized to develop a working hypothesis to design supramolecular gelators derived from simple organic salts. The activity not only provided a way to occasionally predict gelation, but also afforded clear understanding of the structural landscape of such supramolecular materials. Without waiting for an ab initio approach for designing a gel, a large number of supramolecular gelators derived from organic salts were designed following the working hypothesis thus developed. Organic salts possess a number of advantages in terms of their ease of synthesis, purification, high yield and stability and, therefore, are suitable for developing materials for various applications. Organic salt-based gel materials for containing oil spills, synthesizing inorganic nanostructures and metal nanoparticles, sensing hazardous gas and dissolved glucose, adsorbing dyes, and facilitating drug delivery in self-delivery fashion have been developed. The journey through the soft world of gelators which was started merely by serendipity turned out to be rewarding, despite the challenges and frustrations in the field. Full article

Amphiphilic peptides can be self-assembled by establishing physical cross-links involving hydrogen bonds and electrostatic interactions with divalent ions. The derived hydrogels have promising properties due to their biocompatibility, reversibility, trigger capability, and tunability. Peptide hydrogels can mimic the extracellular matrix and favor the growth of hydroxyapatite (HAp) as well as its encapsulation. Newly designed materials offer great perspectives for applications in the regeneration of hard tissues such as bones, teeth, and cartilage. Furthermore, development of drug delivery systems based on HAp and peptide self-assembly is attracting attention. Full article

In the presence of water, poly(N-acryloyl glycinamide) homopolymers form highly swollen hydrogels that undergo fast and reversible gel↔sol transitions on heating. According to the literature, the transition temperature depends on concentration and average molecular weight, and in the case of copolymers, composition and hydrophilic/hydrophobic character. In this article, we wish to introduce new copolymers made by free radical polymerization of mixtures of N-acryloyl glycinamide and of its analog optically active N-acryloyl l-alaninamide in various proportions. The N-acryloyl l-alaninamide monomer was selected in attempts to introduce hydrophobicity and chirality in addition to thermo-responsiveness of the Upper Critical Solubilization Temperature-type. The characterization of the resulting copolymers included solubility in solvents, dynamic viscosity in solution, Fourrier Transform Infrared, Nuclear Magnetic Resonance, and Circular Dichroism spectra. Gel→sol transition temperatures were determined in phosphate buffer (pH = 7.4, isotonic to 320 mOsm/dm³). The release characteristics of hydrophilic Methylene Blue and hydrophobic Risperidone entrapped in poly(N-acryloyl glycinamide) and in two copolymers containing 50 and 75% of alanine-based units, respectively, were compared. It was found that increasing the content in N-acryloyl-alaninamide-based units increased the gel→sol transition temperature, decreased the gel consistency, and increased the release rate of Risperidone, but not that of Methylene Blue, with respect to homo poly(N-acryloyl glycinamide). The increase observed in the case of Risperidone appeared to be related to the hydrophobicity generated by alanine residues. Full article

The production of porous materials based on starch has been explored with supercritical drying—yielding aerogel—and freeze-drying. The two drying procedures were applied on the same gelling solution of amylomaize starch pasted at 140 °C and for two concentrations (5 and 10 wt.%). After gelation and retrogradation, water from the samples to be supercritically dried was exchanged to ethanol. The resulting starch aerogel presented high specific surface area (197 m²/g). Freeze-drying was assessed by investigating the effect of the gelation, retrogradation, freezing temperature, and sublimation pressure. The resulting starch materials were macroporous, with limited specific surface area and limited mechanical integrity. Cohesive open cell foam with pore size of ~20 µm was produced by quenching the hot starch melt in liquid nitrogen. The highest specific surface area obtained with freeze-drying was 7.7 m²/g for the hot starch melt frozen at −20 °C. Full article

Chitosan beads attract interest in diverse applications, including drug delivery, biocatalysis and water treatment. They can be formed through several supramolecular pathways, ranging from phase inversion in alkaline solutions, to the ionic crosslinking of chitosan with multivalent anions, to polyelectrolyte or surfactant/polyelectrolyte complexation. Many chitosan bead uses require control over their stability to dissolution. To help elucidate how this stability depends on the choice of supramolecular gelation chemistry, we present a comparative study of chitosan bead stability in acidic aqueous media using three common classes of supramolecular chitosan beads: (1) alkaline solution-derived beads, prepared through simple precipitation in NaOH solution; (2) ionically-crosslinked beads, prepared using tripolyphosphate (TPP); and (3) surfactant-crosslinked beads prepared via surfactant/polyelectrolyte complexation using sodium salts of dodecyl sulfate (SDS), caprate (NaC₁₀) and laurate (NaC₁₂). Highly variable bead stabilities with dissimilar sensitivities to pH were achieved using these methods. At low pH levels (e.g., pH 1.2), chitosan/SDS beads were the most stable, requiring roughly 2 days to dissolve. In weakly acidic media (at pH 3.0–5.0), however, chitosan/TPP beads exhibited the highest stability, remaining intact throughout the entire experiment. Beads prepared using only NaOH solution (i.e., without ionic crosslinking or surfactant complexation) were the least stable, except at pH 5.0, where the NaC₁₀ and NaC₁₂-derived beads dissolved slightly faster. Collectively, these findings provide further guidelines for tailoring supramolecular chitosan bead stability in acidic media. Full article

The RTX domains found in some pathogenic proteins encode repetitive peptide sequences that reversibly bind calcium and fold into the unique the β-roll secondary structure. Several of these domains have been studied in isolation, yielding key insights into their structure/function relationships. These domains are increasingly being used in protein engineering applications, where the calcium-induced control over structure can be exploited to gain new functions. Here we review recent advances in the use of RTX domains in the creation of calcium responsive biomaterials. Full article

Proteins are receiving significant attention for the production of structures for the encapsulation of active compounds, aimed at their use in food products. Proteins are one of the most used biomaterials in the food industry due to their nutritional value, non-toxicity, biodegradability, and ability to create new textures, in particular, their ability to form gel particles that can go from macro- to nanoscale. This review points out the different techniques to obtain protein-based nanostructures and their use to encapsulate and release bioactive compounds, while also presenting some examples of food grade proteins, the mechanism of formation of the nanostructures, and the behavior under different conditions, such as in the gastrointestinal tract. Full article

Polyampholyte cryogels are a less considered subject in comparison with cryogels based on nonionic, anionic and cationic precursors. This review is devoted to physicochemical behavior, complexation ability and catalytic properties of cryogels based on amphoteric macromolecules. Polyampholyte cryogels are able to exhibit the stimuli-responsive behavior and change the structure and morphology in response to temperature, pH of the medium, ionic strength and water–organic solvents. Moreover, they can uptake transition metal ions, anionic and cationic dyes, ionic surfactants, polyelectrolytes, proteins, and enzymes through formation of coordination bonds, hydrogen bonds, and electrostatic forces. The catalytic properties of polyampholyte cryogels themselves and with immobilized metal nanoparticles suspended are outlined following hydrolysis, transesterification, hydrogenation and oxidation reactions of various substrates. Application of polyampholyte cryogels as a protein-imprinted matrix for separation and purification of biomacromolecules and for sustained release of proteins is demonstrated. Comparative analysis of the behavior of polyampholyte cryogels with nonionic, anionic and cationic precursors is given together with concluding remarks. Full article

Relatively smaller volumes of gelling systems had been used to address conformance problems located near the wellbore in oil reservoirs with harsh temperature and salinity conditions. These gelling systems were formulated with high concentrations of low-molecular-weight acrylamide-based polymers crosslinked with polyethylenimine (PEI). However, for in-depth conformance control, in which large gelant volumes and long gelation times were required, lower-base polymer loadings were necessary to ensure the economic feasibility of the treatment. In this study, a gelling system with high-molecular weight 2-acrylamido-2-methylpropane sulfonic acid (AMPS), N-vinyl-2-pyrrolidone (NVP), acrylamide terpolymer, and PEI, with the addition of bentonite as a filler, was formulated. The influence of the gelant formulation and reservoir conditions on the gelation kinetics and final gel strength of the system was investigated through bottle tests and rheological tests. The addition of clay in the formulation increased the gelation time, thermal stability, and syneresis resistance, and slightly improved the final gel strength. Furthermore, samples prepared with polymer and PEI concentrations below 1 wt %, natural bentonite, and PEI with molecular weight of 70,000 kg/kmol and pH of 11: (i) presented good injectivity and propagation parameters (pseudoplastic behavior and viscosity ~25 mPa·s); (ii) showed suitable gelation times for near wellbore (~5 h) or far wellbore (~21 h) treatments; and (iii) formed strong composite hydrogels (equilibrium complex modulus ~10–20 Pa and Sydansk code G to H) with low syneresis and good long-term stability (~3 to 6 months) under harsh conditions. Therefore, the use of high-molecular-weight base polymer and low-cost clay as active filler seems promising to improve the cost-effectiveness of gelling systems for in-depth conformance treatments under harsh conditions of temperature and salinity/hardness. Full article

The effect of glycerol (GLY) and poly(ethylene glycol) (PEG) additives on the properties of silica aerogel-like monoliths obtained from methyltrimethoxysilane (MTMS) precursor was assessed. The tested molar ratios of additive/precursor were from 0 to 0.1 and the lowest bulk densities were obtained with a ratio of 0.025. When a washing step was performed in the sample containing the optimum PEG ratio, the bulk density could be reduced even further. The analysis of the material’s microstructure allowed us to conclude that GLY, if added in an optimum amount, originates a narrower pore size distribution with a higher volume of mesopores and specific surface area. The PEG additive played a binder effect, leading to the filling of micropores and the appearance of large pores (macropores), which caused a reduction in the specific surface area. The reduction of the bulk density and the microstructural changes in the aerogels induced by adding a small amount of these additives confirm the possibility of fine control of properties of these lightweight materials. The achieved high porosity (97%) and low thermal conductivity (~35 mW·m⁻¹·K⁻¹) makes them suitable to be used as thermal insulators. Full article

In this work, we present Thioflavin T fluorescence, transmission electron microscopy (TEM), circular dichroism (CD), Fourier-transformed infrared (FT-IR), and oscillatory rheometry studies applied to an antineoplastic drug, 5-fluorouracil (5-FU), embedded in a heterochiral tripeptide hydrogel to obtain a drug delivery supramolecular system. The release of 5-fluorouracil was monitored over time by reverse-phase high-performance liquid chromatography (HPLC) and its interaction with the tripeptide assemblies was probed by all-atom molecular dynamics simulations. Full article

Chemically cross-linkable gelatin methacryloyl (GM) derivatives are getting increasing attention regarding biomedical applications. Thus, thorough investigations are needed to achieve full understanding and control of the physico-chemical behavior of these promising biomaterials. We previously introduced gelatin methacryloyl acetyl (GMA) derivatives, which can be used to control physical network formation (solution viscosity, sol-gel transition) independently from chemical cross-linking by variation of the methacryloyl-to-acetyl ratio. It is known that temperature dependent physical network formation significantly influences the mechanical properties of chemically cross-linked GM hydrogels. We investigated the temperature sensitivity of GM derivatives with different degrees of modification (GM2, GM10), or similar degrees of modification but different methacryloyl contents (GM10, GM2A8). Rheological analysis showed that the low modified GM2 forms strong physical gels upon cooling while GM10 and GM2A8 form soft or no gels. Yet, compression testing revealed that all photo cross-linked GM(A) hydrogels were stronger if cooling was applied during hydrogel preparation. We suggest that the hydrophobic methacryloyl and acetyl residues disturb triple helix formation with increasing degree of modification, but additionally form hydrophobic structures, which facilitate chemical cross-linking. Full article