Gels, Volume 6, Issue 4 (December 2020) – 19 articles

The incorporation of cyclodextrins into polymeric crosslinked gels of hydrophilic nature can be useful for promoting the sorption of hydrophobic molecules and/or modulating the release of active principles. The covalent addition of these excipients to the matrix integrates their solubilizing effect that can contribute to increase the capacity of retention of hydrophobic substances. In this study, three diverse polysaccharides, chitosan, xanthan gum, and locust bean gum, were crosslinked with or without β-cyclodextrin, using citric acid in different ratios, to create hydrogel matrices. Through a green synthetic path, the efficient production of soluble and insoluble (hydrogel) networks functionalized with β-cyclodextrin was achieved by means of a solventless procedure. The characterization of their chemical composition, swelling in water, and their sorption and release behavior were also carried out in this work. Full article

Wide-pore proteinaceous freeze–thaw spongy gels were synthesized via the cryotropic gelation technique using the bovine blood serum or its diluted solutions as the protein-containing precursors. The feed systems also included the denaturant (urea) and the thiol-reductant (cysteine). The gel-fraction yield decreased and the swelling degree of the walls of macropores in such heterophase matrices increased with decreasing the initial protein concentration. The optimum freezing temperature was found to be within a rather narrow range from −15 to −20 °C. In this case, the average size of the macropores in the resultant cryogels was 90–110 μm. The suitability of such soft wide-pore gel materials for the application as the carriers of peptide bioregulators was demonstrated in the in vitro experiments, when the posterior segments of the Pleurodeles waltl adult newts’ eyes were used as a model biological target. It was shown that a statistically reliable protective effect on the state of the sclera, vascular membrane and retinal pigment epithelium, as well as on the viability of fibroblasts, was inherent in the proteinaceous cryogels loaded with the peptide bioregulator (Viophtan-5™) isolated from the bovine eye sclera. Full article

Novel sodium carboxymethyl cellulose-g-poly (sodium acrylate)/Ferric chloride (CMC-g-PNaA/FeCl₃) nanoporous hydrogel beads were prepared based on the ionic cross-linking between CMC-g-PNaA and FeCl₃. The structure of CMC and CMC-g-PNaA were elucidated by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy, and the elemental composition was analyzed by energy dispersive X-ray analysis (EDX). The physicochemical properties of the CMC-g-PNaA/FeCl₃ hydrogel beads were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM) and thermogravimetric analysis (TGA). The swelling percentage of hydrogel beads was studied at different time periods. The obtained CMC-g-PNaA/FeCl₃ hydrogel beads exhibited a higher nanoporous morphology than those of CMC-g-PNaA and CMC beads. Furthermore, an AFM image of the CMC-g-PNaA/FeCl₃ beads shows granule type topology. Compared to the CMC-g-PNaA (189 °C), CMC-g-PNaA/FeCl₃ hydrogel beads exhibited improvement in thermal stability (199 °C). Furthermore, CMC-g-PNaA/FeCl₃ hydrogel beads depicted a higher swelling percentage capacity of around 1452%, as compared to CMC-g-PNaA (1096%). Moreover, this strategy with preliminary results could be useful for the development of polysaccharide-based hybrid hydrogel beads for various potential applications. Full article

The development of distinct biomimetic microenvironments for regulating stem cell behavior and bioengineering human tissues and disease models requires a solid understanding of cell–substrate interactions, adhesion, and its role in directing cell behavior, and other physico-chemical cues that drive cell behavior. In the past decade, innovative developments in chemistry, materials science, microfabrication, and associated technologies have given us the ability to manipulate the stem cell microenvironment with greater precision and, further, to monitor effector impacts on stem cells, both spatially and temporally. The influence of biomaterials and the 3D microenvironment’s physical and biochemical properties on mesenchymal stem cell proliferation, differentiation, and matrix production are the focus of this review chapter. Mechanisms and materials, principally hydrogel and hydrogel composites for bone and cartilage repair that create “cell-supportive” and “instructive” biomaterials, are emphasized. We begin by providing an overview of stem cells, their unique properties, and their challenges in regenerative medicine. An overview of current fabrication strategies for creating instructive substrates is then reviewed with a focused discussion of selected fabrication methods with an emphasis on bioprinting as a critical tool in creating novel stem cell-based biomaterials. We conclude with a critical assessment of the current state of the field and offer our view on the promises and potential pitfalls of the approaches discussed. Full article

Collagen-based hydrogels are investigated extensively in tissue engineering for their tunable physiochemical properties, biocompatibility and biodegradability. However, the effect of the integrity of the collagen triple helical structure on biodegradability is yet to be studied. In this study, we monitored the degradation of intact collagen (C-coll) and hydrolyzed collagen (D-coll) hydrogels in collagenase Clostridium histolyticum to understand their degradation process. Our results show that when peptides are present on the surface of the fibrils of D-coll hydrogels, cleavage of amide bonds occur at a much higher rate. The fibrillar structure of D-coll hydrogel results in a more pronounced breakdown of the gel network and dissolution of collagen peptides. The results from this work will improve the understanding of enzymatic degradation and the resulting bioabsorption of collagen materials used in drug delivery systems and scaffolds. Full article

Different numerical solutions of a previously developed mass transport model for supercritical drying of aerogel particles in a packed bed [Part 1: Selmer et al. 2018, Part 2: Selmer et al. 2019] are compared. Two finite difference discretizations and a finite volume method were used. The finite volume method showed a higher overall accuracy, in the form of lower overall Euclidean norm ($l_2$) and maximum norm ($l_{\infty }$) errors, as well as lower mole balance errors compared to the finite difference methods. Additionally, the finite volume method was more efficient when the condition numbers of the linear systems to be solved were considered. In case of fine grids, the computation time of the finite difference methods was slightly faster but for 16 or fewer nodes the finite volume method was superior. Overall, the finite volume method is preferable for the numerical solution of the described drying model for aerogel particles in a packed bed. Full article

The most difficult issue when using tissue engineering products is enabling the ability to store them without losing their restorative capacity. The numbers and viability of mesenchymal stem cells encapsulated in a hydrogel scaffold after cryostorage at −80 °C (by using, individually, two kinds of cryoprotectors—Bambanker and 10% DMSO (Dimethyl sulfoxide) solution) for 3, 6, 9, and 12 months were determined, with subsequent assessment of cell proliferation after 96 h. The analysis of the cellular component was performed using fluorescence microscopy and the two fluorochromes—Hoechst 3334 and NucGreenTM Dead 488. The experimental protocol ensured the preservation of cells in the scaffold structure, retaining both high viability and proliferative activity during storage for 3 months. Longer storage of scaffolds led to their significant changes. Therefore, after 6 months, the proliferative activity of cells decreased. Cryostorage of scaffolds for 9 months led to a decrease in cells’ viability and proliferative activity. As a result of cryostorage of scaffolds for 12 months, a decrease in viability and proliferative activity of cells was observed, as well as pronounced changes in the structure of the hydrogel. The described scaffold cryostorage protocol could become the basis for the development of storage protocols for such tissue engineering products, and for helping to extend the possibilities of their clinical use while accelerating their commercialization. Full article

In this work, oleogels of cocoa butter (CB), rice bran oil (RBO), and graphene oxide (GO) were prepared. The prepared oleogels were subjected to various characterization techniques such as bright-field microscopy, X-ray diffraction (XRD), crystallization kinetics, differential scanning calorimetry (DSC), and mechanical studies. The influence of increasing GO content on the in vitro drug release and ex vivo corneal permeation of the model drug (ciprofloxacin HCl—CPH) from the oleogels was also investigated. Bright-field micrographs showed that increment in GO content reduced the size of the globular particles of CB. XRD analysis revealed that CB was crystallized in its β’ and β polymorphic forms in the oleogels, which was in agreement with thermal studies. The mechanical characterization demonstrated that the presence of GO improved the elastic nature and stress-bearing properties of the oleogels. Moreover, GO altered the crystallization kinetics of CB in the oleogels in a composition-dependent manner. The in vitro release of CPH from the oleogels occurred through either Fickian diffusion or fat network relaxation or a combination thereof. Furthermore, the inclusion of GO enhanced the ex vivo permeation of CPH molecules across the caprine cornea. Hence, we concluded that the prepared oleogels could be explored as potential delivery systems for ophthalmic applications. Full article

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro. Full article

The role of specific interactions in the self-assembly process of low molecular weight gelators (LMWGs) was studied by altering the nonbonding interactions responsible for gel formation via structural modification of the gelator/nongelator. This was achieved by modifying pyridyl moieties of bis(pyridyl) urea-based hydrogelator (4–BPU) and the isomer (3–BPU) to pyridyl N–oxide compounds (L₁ and L₂, respectively). The modification of the functional groups resulted in the tuning of the gelation properties of the parent gelator, which induced/enhanced the gelation properties. The modified compounds displayed better mechanical and thermal stabilities and the introduction of the N–oxide moieties had a prominent effect on the morphologies of the gel network, which was evident from the scanning electron microscopy (SEM) images. The effect of various interactions due to the introduction of N–oxide moieties in the gel network formation was analyzed by comparing the solid-state interactions of the compounds using single crystal X-ray diffraction and computational studies, which were correlated with the enhanced gelation properties. This study shows the importance of specific nonbonding interactions and the spatial arrangement of the functional groups in the supramolecular gel network formation. Full article

We present a mean field theory to describe cholesteric elastomers and gels under an external field, such as an electric or a magnetic field, along the helix axis of a cholesteric phase. We study the deformations and volume phase transitions of cholesteric gels as a function of the external field and temperature. Our theory predicts the phase transitions between isotropic (I), nematic (N), and heliconical cholesteric ($C{h}_H)$ phases and the deformations of the elastomers at these phase transition temperatures. We also find volume phase transitions at the $I-C{h}_H$ and the $N-C{h}_H$ phase transitions. Full article

Antioxidants are known to improve the wound healing process and are researched as a therapeutic strategy to treat chronic wounds. Dopamine is a known neurotransmitter with antioxidant properties that can be polymerized to form polydopamine (PDA). Herein, polydopamine is demonstrated as an antioxidant biomaterial. In prior work, we developed methodology to prepare hydrogels by crosslinking polysaccharides with polyamines via epichlorohydrin and NaOH. Using this previously developed methodology, dextran hydrogels crosslinked with polydopamine were prepared. Darkening of the gels indicated the increasing incorporation of polydopamine within the hydrogels. In addition to basic pH, polydopamine can be formed by reaction with polyethylene imine (PEI), which results in PEI-PDA copolymer. Dextran was similarly crosslinked with the PEI-PDA copolymer and resulted in sturdier, darker gels, which had more polydopamine incorporated. Hydrogel morphology and strength were dependent on the feed ratios of dopamine. Antioxidant activity of polydopamine containing hydrogel was confirmed and shown to be dependent on the amount of dopamine used in hydrogel synthesis. Hydrogels with 0.5 dopamine to dextran feed ratio scavenged 78.8% of radicals in a 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant assay while gels with no dopamine scavenged only 1.4% of radicals. An ex vivo wound healing assay showed considerable cell migration with the PEI-PDA containing hydrogel. Full article

Tetraethyl orthosilicate (TEOS)-based hydrogels, with shear stress response and drug releasing properties, can be formulated simply by TEOS hydrolysis followed by volume corrections with aqueous solvents and pH adjustments. Such basic thixotropic hydrogels (thixogels) form via the colloidal aggregation of nanoparticulate silica. Herein, we investigated the effects of the nanoparticulate building blocks on the drug release properties of these materials. Our data indicate that the age of the hydrolyzed TEOS used for the formulation impacts the nanoparticulate structure and stiffness of thixogels. Moreover, the mechanism of formation or the disturbance of the nanoparticulate network significantly affects the release profiles of the incorporated drug. Collectively, our results underline the versatility of these basic, TEOS-only hydrogels for drug delivery applications. Full article

Collagen is the most abundant protein in mammals and possesses high biocompatibility and low antigenicity. These biological properties render it one of the most useful biomaterials for medical applications. This study investigated the mechanical and physical characteristics of collagen hydrogels cross-linked with different ratios of polyvinylpyrrolidone capped zinc oxide nanoparticles (ZPVP). Fourier transform infrared spectroscopy indicated molecular interactions between collagen fibers and ZPVP. Texture analysis revealed a significant increase in gel hardness, adhesiveness, and viscosity after cross-linking with ZPVP. Rheological measurements showed that as the ratio of ZPVP increased, stronger hydrogels were formed which in turn resulted in more sustained release of the model drug, dexamethasone sodium phosphate. We can therefore conclude that the mechanical properties of collagen hydrogels can be modified by controlling the ratio of ZPVP used for cross-linking, offering the potential to develop biocompatible sustained release drug delivery systems. Full article

Type I collagen and fibrin are two essential proteins in tissue regeneration and have been widely used for the design of biomaterials. While they both form hydrogels via fibrillogenesis, they have distinct biochemical features, structural properties and biological functions which make their combination of high interest. A number of protocols to obtain such mixed gels have been described in the literature that differ in the sequence of mixing/addition of the various reagents. Experimental and modelling studies have suggested that such co-gels consist of an interpenetrated structure where the two proteins networks have local interactions only. Evidences have been accumulated that immobilized cells respond not only to the overall structure of the co-gels but can also exhibit responses specific to each of the proteins. Among the many biomedical applications of such type I collagen-fibrin mixed gels, those requiring the co-culture of two cell types with distinct affinity for these proteins, such as vascularization of tissue engineering constructs, appear particularly promising. Full article

In this work, a cellular automata (CA) approach was used to generate 3D structures of polyamide and carbon aerogels. Experimental results are used as initial data for materials’ digital representations and to verify the developed CA models. Based on the generated digital structures, a computer study of aerogels’ mechanical properties was conducted. The offered CA models can be applied for the development of new nanoporous materials such as aerogels of different nature and allow for a reduction in the amount of required full-scale experiments, consequently decreasing development time and costs of new material formulations. Full article

Poly(N-isopropylacrylamide) (PNIPAM) hydrogel microparticles with different core–shell morphologies have been designed, while maintaining an unvaried chemical composition: a morphology with (i) an un-crosslinked core with a crosslinked shell of PNIPAM chains and (ii) PNIPAM chains crosslinked to form the core with a shell consisting of tethered un-crosslinked PNIPAM chains to the core. Both morphologies with two different degrees of crosslinking have been assessed by confocal microscopy and tested with respect to their temperature responsivity and deformation by applying an osmotic stress. The thermal and mechanical behavior of these architectures have been framed within a Flory–Rehner modified model in order to describe the microgel volume shrinking occurring as response to a temperature increase or an osmotic perturbation. This study provides a background for assessing to what extent the mechanical features of the microgel particle surface affect the interactions occurring at the interface of a microgel particle with a cell, in addition to the already know ligand/receptor interaction. These results have direct implications in triggering a limited phagocytosis of microdevices designed as injectable drug delivery systems. Full article

The tumor microenvironment is a key modulator in cancer progression and has become a novel target in cancer therapy. An increase in hyaluronan (HA) accumulation and metabolism can be found in advancing tumor progression and are often associated with aggressive malignancy, drug resistance and poor prognosis. Wound-healing related myofibroblasts or activated cancer-associated fibroblasts (CAF) are assumed to be the major sources of HA. Both cell types are capable to synthesize new matrix components as well as reorganize the extracellular matrix. However, to which extent myofibroblasts and CAF perform these actions are still unclear. In this work, we investigated the matrix remodeling and HA production potential in normal human dermal fibroblasts (NHFB) and CAF in the absence and presence of transforming growth factor beta -1 (TGF-β1), with TGF-β1 being a major factor of regulating fibroblast differentiation. Three-dimensional (3D) collagen matrix was utilized to mimic the extracellular matrix of the tumor microenvironment. We found that CAF appeared to response insensitively towards TGF-β1 in terms of cell proliferation and matrix remodeling when compared to NHFB. In regards of HA production, we found that both cell types were capable to produce matrix bound HA, rather than a soluble counterpart, in response to TGF-β1. However, activated CAF demonstrated higher HA production when compared to myofibroblasts. The average molecular weight of produced HA was found in the range of 480 kDa for both cells. By analyzing gene expression of HA metabolizing enzymes, namely hyaluronan synthase (HAS1-3) and hyaluronidase (HYAL1-3) isoforms, we found expression of specific isoforms in dependence of TGF-β1 present in both cells. In addition, HAS2 and HYAL1 are highly expressed in CAF, which might contribute to a higher production and degradation of HA in CAF matrix. Overall, our results suggested a distinct behavior of NHFB and CAF in 3D collagen matrices in the presence of TGF-β1 in terms of matrix remodeling and HA production pointing to a specific impact on tumor modulation. Full article