Synthesis of hydrogels from biomaterials and their potential application in tissue engineering.

In this study, a series of hydrogels were synthesized from chitosan(s) that was crosslinking with glutaraldehyde at different concentrations. Ascorbic acid in an acidic medium was used to facilitate non-covalent interactions. The chitosan(s) was obtained from shrimp cytoskeleton; while ascorbic acid was extracted from xoconostle juice. The hydrogel reaction was monitored by UV-vis spectroscopy (550 nm) to determine the reaction kinetics and reaction order at 60 °C. The hydrogels structures were characterized by NMR, FT-IR, HR-MS and SEM, while the degree of cross-linking was examined with TGA-DA. The extracellular matrices were obtained as stable hydrogels where reached maximum crosslinking was of 7 %, independent of glutaraldehyde quantity added. The rheological properties showed a behavior of weak gels and a dependence of crosslinking agent concentration on strength at different temperatures. The cytotoxicity assay showed that the gels had no adverse effects on cellular growth for all concentrations of glutaraldehyde.

Synthesis and Characterization of Cassava Gum Hydrogel Associated with Chlorhexidine and Evaluation of Release and Antimicrobial Activity.

Hydrogels from natural sources are attracting increasing interest due to their ability to protect biologically active molecules. Starch extracted from cassava tubers is a promising material for synthesizing these hydrogels. Copolymerization of cassava gum and incorporation of chlorhexidine digluconate (CLX) into the hydrogels is confirmed by changes in the crystallographic profile, as observed through X-ray diffraction, and a shift in the 1000 cm-1 band in the Fourier-transform infrared spectroscopy spectrum. The differential scanning calorimetry reveals changes in the decomposition temperature of the synthesized hydrogels related to CLX volatility. Micrographs illustrate the material's porosity. Release tests indicate a constant linear release over 72 h, while antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans is satisfactory, with 100% effectiveness from 0.5% CLX and the formation of inhibition halos. Toxicity and biocompatibility studies show no cytotoxicity. The continuous release of chlorhexidine is promising for components of biomedical implants and applications as it can ensure antimicrobial action according to specific therapeutic needs.

Chitosan-based hydrogel crosslinked through an aza-Michael addition catalyzed by boric acid.

Polysaccharide-based hydrogels are particularly attractive materials for biomedical applications. However, their use is restricted due to their brittleness and poor mechanical properties. Here, to overcome such limitations, we report an original, green, simple, and efficient strategy to synthesize a polysaccharide-based hydrogel of chitosan (Cht) and a vinyl-functionalized PVA (PVA-MA), a non-toxic synthetic polymer that is widely known to improve the mechanical properties and stability of materials containing polysaccharides. The hydrogel was crosslinked through an aza-Michael addition among the amino groups of Cht with the vinyl moieties of PVA-MA catalyzed by boric acid (B(OH)3), an eco-friendly inorganic compound. Characterization analyses revealed that the prepared hydrogel has a porous-like morphology, an outstanding liquid uptake capacity (>665%), and improved stability in a physiological fluid for long periods. In summary, this original and simple strategy showed to be efficient in the synthesis of hydrogels with attractive properties for the biomedical field application.

Physicochemical and biological characterization of a xanthan gum-polyvinylpyrrolidone hydrogel obtained by gamma irradiation.

Xanthan gum (XG) and polyvinylpyrrolidone (PVP) are two polymers with low toxicity, high biocompatibility, biodegradability, and high hydrophilicity, making them promising candidates for multiple medical aspects. The present work aimed to synthesize a hydrogel from a mixture of XG and PVP and crosslinked by gamma irradiation. We assessed the hydrogel through a series of physicochemical (FT-IR, TGA, SEM, and percentage of swelling) and biological (stability of the hydrogel in cell culture medium) methods that allowed to determine its applicability. The structural evaluation by infrared spectrum demonstrated that a crosslinked hydrogel was obtained from the combination of polymers. The calorimetric test and swelling percentage confirmed the formation of the bonds responsible for the crosslinked structure. The calorimetric test evidenced that the hydrogel was resistant to decomposition in contrast to non- irradiated material. The determination of the swelling degree showed constant behavior over time, indicating a structure resistant to hydrolysis. This phenomenon also occurred during the test of stability in a cell culture medium. Additionally, microscopic analysis of the sample revealed an amorphous matrix with the presence of porosity. Thus, the findings reveal the synthesis of a novel material that has desirable attributes for its potential application in pharmaceutical and biomedical areas.

Valorization of Artichoke Industrial By-Products Using Green Extraction Technologies: Formulation of Hydrogels in Combination with Paulownia Extracts.

The integral valorization of artichoke bracts generated during industrial canning of artichoke was assessed. The extraction of bioactive compounds was addressed with pressurized hot water under subcritical conditions. The performance of this stage on the extraction of phenolics with antioxidant properties and the saccharidic fraction using conventional and microwave heating was compared. The microwave assisted process was more efficient than the conventional one regarding extraction yields of total solubles, and glucose and fructose oligomers and phenolics, because lower operational temperatures and shorter times were needed. Degradation of fructose oligomers was observed at temperatures higher than 160 °C, whereas the maximal phenolic content occurred at 220 °C. Both the extracts and the residual solids, obtained at conditions leading to maximum phenolics yields, were evaluated for the production of starch-based hydrogels, supplemented with Paulownia leaves' aqueous extracts.

Synthesis and Evaluation of AlgNa-g-Poly(QCL-co-HEMA) Hydrogels as Platform for Chondrocyte Proliferation and Controlled Release of Betamethasone.

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.

Type I collagen hydrogels as a delivery matrix for royal jelly derived extracellular vesicles.

Throughout the last decade, extracellular vesicles (EVs) have become increasingly popular in several areas of regenerative medicine. Recently, Apis mellifera royal jelly EVs (RJ EVs) were shown to display favorable wound healing properties such as stimulation of mesenchymal stem cell migration and inhibition of staphylococcal biofilms. However, the sustained and effective local delivery of EVs in non-systemic approaches - such as patches for chronic cutaneous wounds - remains an important challenge for the development of novel EV-based wound healing therapies. Therefore, the present study aimed to assess the suitability of type I collagen -a well-established biomaterial for wound healing - as a continuous delivery matrix. RJ EVs were integrated into collagen gels at different concentrations, where gels containing 2 mg/ml collagen were found to display the most stable release kinetics. Functionality of released RJ EVs was confirmed by assessing fibroblast EV uptake and migration in a wound healing assay. We could demonstrate reliable EV uptake into fibroblasts with a sustained pro-migratory effect for up to 7 d. Integrating fibroblasts into the RJ EV-containing collagen gel increased the contractile capacity of these cells, confirming availability of RJ EVs to fibroblasts within the collagen gel. Furthermore, EVs released from collagen gels were found to inhibit Staphylococcus aureus ATCC 29213 biofilm formation. Overall, our results suggest that type I collagen could be utilized as a reliable, reproducible release system to deliver functional RJ EVs for wound healing therapies.

Synthesis, Characterization, and In Vitro and In Vivo Evaluations of Cellulose Hydrogels Enriched with Larrea tridentata for Regenerative Applications.

INTRODUCTION: Tissue engineering is an elementary necessity for several applications in the biomedical field through the use of several biopolymers derived from plants. Larrea tridentata (LT) is a very used plant for various medicinal applications with interesting properties; however, its use into cellulose hydrogels for possible regenerative therapeutics is still limited. Cellulose films could be applied in medical field as wound healing, scaffold for connective tissue for periodontal applications, and so on. The aim of this study was to evaluate the mechanical properties and in vivo and in vitro biocompatibility of cellulose hydrogels that have been enriched with LT in a rat model. METHODS: By in vivo and in vitro assays, the concentration of LT was varied from 1 to 5 wt%, respectively. Hydrogel films were implanted intramuscularly into female Wistar rats, 250 g in weight and aged 2 months, to analyze their cytocompatibility and biocompatibility. RESULTS: No case showed any evidence of inflammation or toxicity. Regarding cell morphology and adhesion, the prepared LT cellulose films had better cytocompatibility values than when polystyrene (PS) dishes were used as the control. In all cases, the results suggest that the addition of LT to the hydrogel films did not affect their cytocompatibility or biocompatibility properties and increases their clinical application due to the reported uses of LT. CONCLUSIONS: Cellulose hydrogel films enriched with LT have the potential to be used in the biomedical field acting as regenerative scaffolds.

Coaxial Spinning of All-Cellulose Systems for Enhanced Toughness: Filaments of Oxidized Nanofibrils Sheathed in Cellulose II Regenerated from a Protic Ionic Liquid.

Hydrogels of TEMPO-oxidized nanocellulose were stabilized for dry-jet wet spinning using a shell of cellulose dissolved in 1,5-diazabicyclo[4.3.0]non-5-enium propionate ([DBNH][CO2Et]), a protic ionic liquid (PIL). Coagulation in an acidic water bath resulted in continuous core-shell filaments (CSFs) that were tough and flexible with an average dry (and wet) toughness of ∼11 (2) MJ·m-3 and elongation of ∼9 (14) %. The CSF morphology, chemical composition, thermal stability, crystallinity, and bacterial activity were assessed using scanning electron microscopy with energy-dispersive X-ray spectroscopy, liquid-state nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, pyrolysis gas chromatography-mass spectrometry, wide-angle X-ray scattering, and bacterial cell culturing, respectively. The coaxial wet spinning yields PIL-free systems carrying on the surface the cellulose II polymorph, which not only enhances the toughness of the filaments but facilities their functionalization.

Recent Advances in Elastin-Based Biomaterial.

Elastin is one of the main components of the extracellular matrix; it provides resistance and elasticity to a variety of tissues and organs of the human body, besides participating in cellular signaling. On the other hand, elastin-derived peptides are synthetic biopolymers with a similar conformation and structure to elastin, but these possess the advantage of solubility in aqueous mediums. Due to their biological activities and physicochemical properties, elastin and related peptides may be applied as biomaterials to develop diverse biomedical devices, including scaffolds, hydrogels, and drug delivery systems for tissue engineering. Likewise, the combination of elastin with natural or synthetic polymers has demonstrated to improve the mechanical properties of biomedical products and drug delivery systems. Here we comprehensively describe the physicochemical properties and physiological functions of elastin. Moreover, we offer an overview of the use of elastin and its derivative polymers as biomaterials to develop scaffolds and hydrogels for tissue engineering. Finally, we discuss some perspectives on the employment of these biopolymers to fabricate new biomedical products.

Poly(vinyl alcohol)/cationic tannin blend films with antioxidant and antimicrobial activities.

This study reports the synthesis, characterization and biological properties of films based on poly(vinyl alcohol) (PVA) and a cationic tannin polymer derivative (TN). Films are obtained from polymeric blends by tuning the PVA/TN weight ratios. The materials are characterized through infrared spectroscopy, X-ray photoelectron spectroscopy, contact angle measurements, mechanical analyses, and scanning electron microscopy. More hydrophilic surfaces are created by modulating the PVA and TN concentrations in the blends. Disintegration tests showed that the films present durability in phosphate buffer (pH 7.4) and low stability in simulated gastric fluid (pH 1.2). The film created at 90/10 PVA/TN weight ratio and crosslinked at 109 PVA/glutaraldehyde molar ratio (sample PVA10/TN10) supports the attachment and proliferation of bone marrow mesenchymal stem cells after 7 days of culture. The scaffolding capacity of the PVA10/TN10 surface is compared with titanium, one of the most important biomedical materials used in bone replacements. Also, the PVA/TN films exhibited cytocompatibility, antioxidant and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. These properties make PVA/TN films are candidates for biomedical applications in the tissue engineering field.

Controlled Thermoreversible Formation of Supramolecular Hydrogels Based on Poly(vinyl alcohol) and Natural Phenolic Compounds.

Supramolecular hydrogels have promising applications in a wide variety of fields including 3D bioprinting, sensors and actuators, biomedicine, and controlled drug delivery. This communication reports the facile reversible thermotriggered formation of novel pH-responsive supramolecular hydrogels based on poly(vinyl alcohol) (PVA) bonded via dynamic H-bridge with small phenolic biomolecules. PVA and phenolic compounds form a clear solution when they are physically mixed in water at high temperature, but a fast gelation is produced at room temperature through multiple strong H-bonding interactions. The structure and type of functional groups of different phenolic molecules allow preparing hydrogels with tailor-made viscoelastic properties, controlled low phase transition temperature, and pH-dependent swelling behavior. This combination makes these supramolecular networks very interesting candidates to be used in 3D bioprinting and topical drug delivery of thermolabile biomolecules.

Thermally reversible nanocellulose hydrogels synthesized via the furan/maleimide Diels-Alder click reaction in water.

The study deals with the synthesis of thermally reversible hydrogels from modified cellulose nanofibers via the Diels-Alder "click" reaction in an aqueous medium. "Never-dried" cellulose fibres derived from hardwood were submitted to shearing and surface TEMPO-oxidation before being modified with furfurylamine. The ensuing pendant furan moieties were reacted with a water-soluble bismaleimide via Diels-Alder coupling at 65 °C to produce a hydrogel, whose deconstruction was induced by the corresponding retro-Diels-Alder reaction carried out at 95 °C. Differential scanning calorimetry and rheological measurement were used to characterize the hydrogels. These aqueous cellulosic materials should provide original applications in such areas as strong paper-based artefacts and biocompatible gels.

Full-factorial central composite rotational design for the immobilization of lactase in natural polysaccharide-based hydrogels and hydrolysis of lactose.

A full-factorial central composite rotational design (FFCCRD) was applied for studying the immobilization of lactase in Arabic gum-based and chitosan-based hydrogels, and hydrolysis of lactose. The optimal immobilization capacities of both hydrogels aiming to obtain high immobilized enzyme activity and low released fraction were determined at 25.0 °C, 39.88 mg mL-1 initial enzyme concentration and pH 6.5. The immobilized enzyme activity and released fraction from the Arabic gum-based hydrogel were 0.322 U mg-1 and 0.193, respectively, during the hydrolysis of lactose contained in UHT milk. These values were 0.289 U mg-1 and 0.136, respectively, using a chitosan-based hydrogel. The immobilized enzyme activity and released fraction from these hydrogels during the hydrolysis of standard lactose were 0.246 U mg-1 and 0.407, and 0.211 U mg-1 and 0.245, respectively. The best conditions for the immobilization of lactase and hydrolysis of lactose were achieved by applying FFCCRD, which were compared with experimental results.

Controlled release of antibiotics from photopolymerized hydrogels: Kinetics and microbiological studies.

The development of convenient synthetic methods and improved materials for the production of high load-capacity and biocompatible drug delivery systems is a challenging task with important implications in health sciences. In this work, acrylamide/2-hydroxyethylmethacrylate and N-isopropylacrylamide/2-hydroxyethylmethacrylate hydrogels were synthesized by photopolymerization using energy-efficient green-LEDs. A functionalized silsesquioxane was used as both crosslinker and co-initiator for the photopolymerization. The hybrid organic-inorganic nature of the silsesquioxane improved the resulting hydrogels' properties increasing their swelling capacity and biocompatibility. Additionally, the mild conditions used during the photopolymerization allowed the synthesis of hydrogels in the presence of antibiotics yielding high load-capacity materials in which the drug preserves its molecular structure and antimicrobial activity (as confirmed by HPLC and microbiological assays). The materials were characterized by FTIR, DSC and SEM. Additionally, the kinetics of gels´ swelling and drug release were studied under physiological conditions (pH 7.4 and 37 °C). The results demonstrate how hydrogel composition affects the antibiotics-release kinetics. The final drug release percentage increased with increasing molar fraction of acrylamide or N-isopropylacrylamide and in most cases exceeded 85%. Finally, the antibacterial effect of loaded gels was characterized using a number of assays against Gram negative and Gram positive bacteria. The observed antibacterial effect correlated well with swelling and drug release results. Furthermore, gels are not toxic for isolated erythrocytes as demonstrated by haemolytic tests. Overall, our results indicate that the produced hydrogels are promising materials to develop controlled drug-delivery devices such as capsules, dermatological patches and others.

Polysaccharide-based hydrogels for the immobilization and controlled release of bovine serum albumin.

Arabic gum-based and chitosan-based hydrogels were synthesized through chemical crosslinking for the immobilization and controlled release of bovine serum albumin (BSA) and characterized by Fourier-transform infrared spectrometry, scanning electron microscopy and swelling assays. The degrees of swelling of the Arabic gum-based hydrogel were 13.22 and 22.95 g water per g dried hydrogel at pH 4.5 and 7.0, respectively, whereas the degrees of swelling of the chitosan-based hydrogel were 15.32 and 36.10 g water per g dried hydrogel, respectively. The water absorption mechanism in both hydrogels was non-Fickian, which involves diffusion through pores and macromolecular relaxation of the hydrophilic three-dimensional polymer network. BSA immobilization capacities of the Arabic gum-based and chitosan-based hydrogels after 240 min at pH 4.5 were 71.0 and 175.6 mg protein per g dried hydrogel, respectively. BSA immobilization capacities after 240 min at pH 7.0 were 62.5 and 154.2 mg protein per g dried hydrogel, respectively. The controlled release of BSA from the Arabic gum-based hydrogel was slightly more efficient than that of the chitosan-based hydrogel due to its more porous structure and weaker physiochemical interactions between the polymer network and protein molecule. Both hydrogels could be employed as carriers of proteins and as capsules for food supplements.

Chitosan/chondroitin sulfate hydrogels prepared in [Hmim][HSO4] ionic liquid.

[Hmim][HSO4] ionic liquid (IL) and bio-renewable sources as chitosan (CHT) and chondroitin sulfate (CS) were used to yield hydrogel-based materials (CHT/CS). The use of IL to solubilize both polysaccharides was considered an innovative way based on "green chemistry" principle, aiming the production of CHT/CS blended systems. CHT/CS hydrogels were carried out in homogeneous medium from short dissolution times. The hydrogels were characterized and achieved with excellent stabilities (in the 1.2-10pH range), larger swelling capacities, as well as devoid of cytotoxicity towards the normal VERO and diseased HT29 cells. The CHT/CS hydrogels carried out in [Hmim][HSO4] could be applied in many technological purposes, like medical, pharmaceutical, and environmental fields.

Development and characterization of repellent formulations based on nanostructured hydrogels.

Diseases caused by insects could lead to epidemic scenarios in urban areas and insect repellents are a shield against a wide range of insects, but they need to be safe without compromising efficacy. Ethyl butylacetylaminopropionate (EB) is a synthetic mosquito repellent, which could be used in products for adults and children due to its low-allergenic potential. The aim of this study was to develop and characterize EB and Poloxamer 407 nanoemulsions regarding their droplets mean size, pH, rheological properties, cytotoxicity and in vitro permeation profile. The developed formulations (F1 with 12.5% of EB and F2 with 25% of EB) were compared with a commercial formulation containing 12.5% of EB. Droplets mean size was determined by DLS, and for both nanoemulsions they were around 200 nm; however, the commercial formulation presented a droplets mean size of 10 nm, which could contribute to its high permeation. F1 and F2 presented a gel-like behavior, however F2 presented lower viscosity due to the presence of more EB between the polymer chains preventing them to interact with each other. Also, F2 was less retained by the epidermis when compared to F1 probably due to its lower viscosity. For the cytotoxicity assay only F2, which presented the highest concentration of EB was tested, and it was not toxic to the cells. This result could be also extended to F1 which presented half the EB concentration. The present study demonstrated that EB and Poloxamer 407 nanoemulsions are promising as new insect-repellent formulations.

Conditions for obtaining polyvinyl alcohol/trisodium trimetaphosphate hydrogels as vitreous humor substitute.

Hydrogels are polymeric materials with numerous medical and biological applications because of their physicochemical properties. In this context, the conditions were defined for obtaining a hydrogel with characteristics similar to the vitreous humor using polyvinyl alcohol (PVA) and trisodium trimetaphosphate (STMP). The concentration of PVA (X1 ), PVA/STMP ratio (X2 ), and initial pH (X3 ) were modified, and their effect was analyzed in terms of the refractive index (Y1 ), density (Y2 ), dynamic viscosity (Y3 ), and final pH (Y4 ). The results demonstrated that X1 interferes with Y1 , Y2 , and Y3 , and X2 interferes with Y2 and Y3 . The best condition for obtaining a hydrogel with characteristics similar to the vitreous humor was 4.2586% PVA (wt/wt), STMP/PVA ratio of 1:6.8213 (wt/wt), and initial pH of 9.424. DSC, ATR-FTIR, swelling degree, and AFM analysis confirmed the PVA reticulation with STMP. Furthermore, STMP increased the glass transition temperature and decreased the water uptake of ∼50% of the hydrogels, which can be explained by the crosslinking of PVA chains. Infrared spectroscopy revealed a decrease of hydroxyl bonds and confirmed the reticulation between PVA and STMP. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1386-1395, 2016.

Synthesis, characterization, and catalytic properties of cationic hydrogels containing copper(II) and cobalt(II) ions.

Here, we report the synthesis and characterization of a hydrogel based on ethylene glycol diglycidyl ether (EGDE) and 1,8-diamino-3,6-dioxaoctane (DA). Chemically stable Co(II) and Cu(II) coordination complexes were prepared with this nonsoluble polyelectrolyte, poly(EGDE-DA), and studied by ss-NMR, FT-IR, thermogravimetry, and microscopy. Mesopores were found in all the samples, the thermal stability of the polymer matrix was highly affected by the presence of metal ions, and the (13)C CP-MAS spectrum for the Cu(II)-complex evidenced a significant increase in the reticulation degree by Cu(II) ions. The catalytic activity of these materials on H2O2 activation was studied by electron spin resonance (ESR). The Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2, an anion superoxide (O2(•)¯), and a hydroxyl radical (OH(•)), which diffused into the solution at the time that a decrease in pH was detected. In the same way, the Cu(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2 and OH(•). H2O2 activation by the poly(EGDE-DA) complexes with Co(II) and Cu(II) were applied on the decolorization of solutions of the azo-dye methyl orange (MO). In the presence of 63 mM H2O2, 87% of MO was removed in 10 min with Cu(II)-poly(EGDE-DA) and in 110 min with Co(II)-poly(EGDE-DA). In addition, the pharmaceutical product epinephrine was partially oxidized to adrenochrome by the O2(•)¯ released from the Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system.