Gels, Volume 5, Issue 2 (June 2019) – 14 articles

Hydrogels and their medical applications in tissue engineering have been widely studied due to their three-dimensional network structure, biocompatibility, and cell adhesion. However, the development of an artificial bile duct to replace the recipient’s tissue is still desired. Some challenges remain in the tissue engineering field, such as infection due to residual artifacts. In other words, at present, there are no established technologies for bile duct reconstruction as strength and biocompatibility problems. Therefore, this study investigated hydrogel as an artificial bile duct base material that can replace tissue without any risk of infectious diseases. First, an antibacterial agent (ABA), Finibax (an ABA used for the clinical treatment of biliary tract infection), was immobilized in gelatin using a crosslinking agent, and the antibacterial properties of the gel and its sustainability were tested. Furthermore, the immobilized amount and the improvement of the proliferation of the human umbilical vein endothelial cells (HUVECs) were cultured as the ABA-Gelatin hydrogel was introduced to prepare a 3D scaffold. Finally, we performed hematoxylin and eosin (H&E) staining after subcutaneous implantation in the rat. Overall, the ABA-Gelatin hydrogel was found to be viable for use in hydrogel applications for tissue engineering due to its good bactericidal ability, cell adhesion, and proliferation, as well as having no cytotoxicity to cells. Full article

Chlorhexidine compounds and their different formulations have been investigated several times, especially in the dentistry field. Chlorhexidine application for mouth rinsing immediately underwent oral contraindications, linked to the possibility of causing pigmentation to the teeth or relating to possible cytotoxic events after oral surgery. The positive effects, however, are considerable and its topical antiseptic action has been widely demonstrated by in vitro and clinical research. That’s the reason for its large application in different fields of dentistry. The aim of this study is to collect all the literature regarding the use of chlorhexidine gel in dentistry and all the numerous applications. The initial search on search engines obtained 232 results; then, following the application of the inclusion criteria there were 24 selected articles. The chlorhexidine gel appliance in the dental daily practice is direct to oral surgery, conservative endodontics, prevention and prophylaxis. The use of chlorhexidine has shown some positive effects, also in the case of systemic diseases prevention. Surely, this topical medicine used both professionally and prescribed for home use, can be considered a great help for the prevention of several oral pathologies with systemic implications too. Full article

Protein-based biopolymers derived from natural tissues possess a hierarchical structure in their native state. Strongly solvating, reducing and stabilizing agents, as well as heat, pressure, and enzymes are used to isolate protein-based biopolymers from their natural tissue, solubilize them in aqueous solution and convert them into injectable or preformed hydrogels for applications in tissue engineering and regenerative medicine. This review aims to highlight the need to investigate the nano-/micro-structure of hydrogels derived from the extracellular matrix proteins of natural tissues. Future work should focus on identifying the nature of secondary, tertiary, and higher order structure formation in protein-based hydrogels derived from natural tissues, quantifying their composition, and characterizing their binding pockets with cell surface receptors. These advances promise to lead to wide-spread use of protein-based hydrogels derived from natural tissues as injectable or preformed matrices for cell delivery in tissue engineering and regenerative medicine. Full article

Because of their inherent biocompatibility and tailorable network design, hydrogels meet an increasing interest as biomaterials for the fabrication of controlled drug delivery devices. In this regard, mathematical modeling can highlight release mechanisms and governing phenomena, thus gaining a key role as complementary tool for experimental activity. Starting from the seminal contribution given by Flory–Rehner equation back in 1943 for the determination of matrix structural properties, over more than 70 years, hydrogel modeling has not only taken advantage of new theories and the increasing computational power, but also of the methods offered by computational chemistry, which provide details at the fundamental molecular level. Simulation techniques such as molecular dynamics act as a “computational microscope” and allow for obtaining a new and deeper understanding of the specific interactions between the solute and the polymer, opening new exciting possibilities for an in silico network design at the molecular scale. Moreover, system modeling constitutes an essential step within the “safety by design” paradigm that is becoming one of the new regulatory standard requirements also in the field-controlled release devices. This review aims at providing a summary of the most frequently used modeling approaches (molecular dynamics, coarse-grained models, Brownian dynamics, dissipative particle dynamics, Monte Carlo simulations, and mass conservation equations), which are here classified according to the characteristic length scale. The outcomes and the opportunities of each approach are compared and discussed with selected examples from literature. Full article

We prepared the small pseudopeptide Lau-l-Dopa(OBn)₂-d-Oxd-OBn (Lau = lauric acid; l-Dopa = l-3,4-dihydroxyphenylalanine; d-Oxd = (4R,5S)-4-methyl-5-carboxyl-oxazolidin-2-one; Bn = benzyl) through a number of coupling reactions between lauric acid, protected l-Dopa and d-Oxd with an excellent overall yield. The ability of the product to form supramolecular organogels has been tested with different organic solvents of increasing polarity and compared with the results obtained with the small pseudopeptide Fmoc-l-Dopa(OBn)₂-d-Oxd-OBn. The mechanical and rheological properties of the organogels demonstrated solvent-dependent properties, with a storage modulus of 82 kPa for the ethanol organogel. Finally, to have a preliminary test of the organogels’ ability to adsorb pollutants, we treated a sample of the ethanol organogel with an aqueous solution of Rhodamine B (RhB) for 24 h. The water solution slowly lost its pink color, which became trapped in the organogel. Full article

The segregative phase separation behavior of biopolymer mixtures composed entirely of polysaccharides was investigated. First, the electrical, optical, and rheological properties of alginate, modified beet pectin, and unmodified beet pectin solutions were characterized to determine their electrical charge, molecular weight, solubility, and flow behavior. Second, suitable conditions for inducing phase segregation in biopolymer mixtures were established by measuring biopolymer concentrations and segregation times. Third, alginate–beet pectin mixtures were blended at pH 7 to promote segregation and the partitioning of the biopolymers between the upper and lower phases was determined using UV–visible spectrophotometry, colorimetry, and calcium sensitivity measurements. The results revealed that phase separation depended on the overall biopolymer concentration and the degree of biopolymer hydrophobicity. A two-phase system could be formed when modified beet pectins (DE 68%) were used but not when unmodified ones (DE 53%) were used. Our measurements demonstrated that the phase separated systems consisted of a pectin-rich lower phase and an alginate-rich upper phase. These results suggest that novel structures may be formed by utilization of polysaccharide–polysaccharide phase separation. By controlling the product formulation and processing conditions it may therefore be possible to fabricate biopolymer particles with specific dimensions, shapes, and internal structures. Full article

Wide-pore cryostructurates were prepared via freezing sodium alginate aqueous solutions with subsequent ice sublimation from the frozen samples, followed by their incubation in the ethanol solutions of calcium chloride or sulfuric acid, rinsing, and final drying. Such sequence of operations resulted in the calcium alginate or alginic acid sponges, respectively. The swelling degree of the walls of macropores in such matrices decreased with increasing polymer concentration in the initial solution. The dependence of the degree of swelling on the cryogenic processing temperature had a bell-like character with a maximum for the samples formed at −20 °C. According to ¹H NMR spectroscopy, the content of mobile (non-frozen) water in the frozen water-sodium alginate systems also depended on the initial polymer concentration and freezing temperature. The cryostructurates obtained did not lose their integrity in water, saline, in an acidic medium at pH 2 for at least three weeks. Under alkaline conditions at pH 12 the first signs of dissolution of the Ca-alginate sponge arose only after a week of incubation. Microbiological testing of the model depot form of the antibiotics entrapped in the Ca-alginate cryostructurate demonstrated the efficiency of this system as the antibacterial material. Full article

Hydrogels are tridimensional networks that are able to retain important amounts of water. These soft materials can be obtained through self-assembling processes involving either hydrophilic molecules or polymers, allowing the formation of the corresponding covalently and physically cross-linked networks. Although the applicability of hydrogels in biomedicine has been exponentially growing due to their biocompatibility and different responses to stimuli, these materials have exhibited the particular feature of poor mechanical strength, and consequently, are brittle materials with low deformation. Due to this reason, a race has started to obtain more stretchable and tough hydrogels through different approaches. Within this context, this review article describes the most representative strategies and examples involving synthetic polymers with potential for biomedical applications. Full article

In this work, the mechanical properties and stability of alginate hydrogels containing functionalized alginates (peptide and β-cyclodextrin) were studied. There is an increasing interest in the modification of alginates to add functions such as cell attachment and increased solubility of hydrophobic drugs, for better performance in tissue engineering and drug release, respectively. Functionalization was achieved in this study via periodate oxidation followed by reductive amination, previously shown to give a high and controllable degree of substitution. Young’s modulus and the stress at rupture of the hydrogels were in general lowered when exchanging native alginate with the modified alginate. Still, the gel strength could be adjusted by the fraction of modified alginate in the mixed hydrogels as well as the degree of oxidation. No notable difference in deformation at rupture was observed while syneresis was influenced by the degree of oxidation and possibly by the nature and amount of the grafted molecules. The mixed hydrogels were less stable than hydrogels with only native alginate, and modified alginate was released from the hydrogels. Furthermore, the hydrogels in general rather disintegrated than swelled upon saline treatments. Full article

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