Development of Gelatin‐Alginate Hydrogels for Burn Wound Treatment

Hydrogels are interesting as wound dressing for burn wounds to maintain a moist environment. Especially gelatin and alginate based wound dressings show strong potential. Both polymers are modified by introducing photocrosslinkable functionalities and combined to hydrogel films (gel‐MA/alg‐MA). In one protocol gel‐MA films are incubated in alg‐MA solutions and crosslinked afterward into double networks. Another protocol involves blending both and subsequent photocrosslinking. The introduction of alginate into the gelatin matrix results in phase separation with polysaccharide microdomains in a protein matrix. Addition of alg(‐MA) to gel‐MA leads to an increased swelling compared to 100% gelatin and similar to the commercial Aquacel Ag dressing. In vitro tests show better cell adhesion for films which have a lower alginate content and also have superior mechanical properties. The hydrogel dressings exhibit good biocompatibility with adaptable cell attachment properties. An adequate gelatin‐alginate ratio should allow application of the materials as wound dressings for several days without tissue ingrowth.     

Novel Poly(amidoamine)-Based Hydrogels as Scaffolds for Tissue Engineering

Summary: Poly(amidoamine)s are biocompatible biodegradable polymers, which can be easily functionalized with a number of bioactive and biomimetic compounds. Co-polymerization of these polymers with 4-aminobutyl guanidine (agmatine) leads to an RGD mimicking structure. Hydrogels based on this structure showed an enhanced cell adhesion and could be chemically linked to a glass substrate to create a bioadhesive support for cell growth. Preliminary optimization and cell adhesion tests on Madin-Darby Canine Kidney cells were performed, both on functionalized and non-functionalized structures, with promising results.     

Characterisation of Redox Initiators for Producing Poly(Vinyl Alcohol) Hydrogels

Summary: This work focuses on the characterisation of ascorbic acid/persulphate initiating system. Three different persulphates were used (ammonium, potassium and sodium), and a range of initiator concentrations were tested. Gel time, gel quality, initiator toxicity, and cell survival upon encapsulation were measured. No significant differences were observed between the three types of persulphates. Higher concentrations of the initiators resulted in faster gel times (5min for 0.05wt% initiator) and higher quality gels (less than 20% sol fraction), although the lower initiator concentrations were better in terms of cell growth inhibition and survival upon encapsulation. Overall, this system shows great promise for use in biomedical applications, however there is a need to minimise the initiator concentration to increase cell compatibility while maintaining a high enough concentration for adequate gel formation.     

Enhanced Cellular Activity in Gelatin‐Poly(Ethylene Glycol) Hydrogels without Compromising Gel Stiffness

Adhesion and proliferation of cells are often suppressed in rigid hydrogels as gel stiffness induces mechanical stress to embedded cells. Herein, the composite hydrogel systems to facilitate high cellular activities are described, while maintaining relatively high gel stiffness. This unusual property is obtained by harmonizing gelatin‐poly(ethylene glycol)‐tyramine (GPT, semisynthetic polymer) and gelatin‐hydroxyphenyl propionic acid conjugates (GH, natural polymer) into hydrogels. A minimum GH concentration of 50% is necessary for cells to be proliferative. GPT is utilized to improve biological stability (>1 week) and gelation time (<20 s) of the hydrogels. These results suggest that deficiency in cellular activity driven by gel stiffness could be overcome by finely tuning the material properties in the microenvironments.

     

Hyaluronic Acid (HA)‐Based Silk Fibroin/Zinc Oxide Core–Shell Electrospun Dressing for Burn Wound Management

Burn injuries represent a major life‐threatening event that impacts the quality of life of patients, and places enormous demands on the global healthcare systems. This study introduces the fabrication and characterization of a novel wound dressing made of core–shell hyaluronic acid–silk fibroin/zinc oxide (ZO) nanofibers for treatment of burn injuries. The core–shell configuration enables loading ZO—an antibacterial agent—in the core of nanofibers, which in return improves the sustained release of the drug and maintains its bioactivity. Successful formation of core–shell nanofibers and loading of zinc oxide are confirmed by transmission electron microscopy, Fourier‐transform infrared spectroscopy, and energy dispersive X‐ray. The antibacterial activity of the dressings are examined against Escherichia coli and Staphylococcus aureus and it is shown that addition of ZO improves the antibacterial property of the dressing in a dose‐dependent fashion. However, in vitro cytotoxicity studies show that high concentration of ZO (>3 wt%) is toxic to the cells. In vivo studies indicate that the wound dressings loaded with ZO (3 wt%) substantially improves the wound healing procedure and significantly reduces the inflammatory response at the wound site. Overall, the dressing introduced herein holds great promise for the management of burn injuries.     

Designing New Antibacterial Wound Dressings: Development of a Dual Layer Cotton Material Coated with Poly(Vinyl Alcohol)_Chitosan Nanofibers Incorporating Agrimonia eupatoria L. Extract

Wounds display particular vulnerability to microbial invasion and infections by pathogenic bacteria. Therefore, to reduce the risk of wound infections, researchers have expended considerable energy on developing advanced therapeutic dressings, such as electrospun membranes containing antimicrobial agents. Among the most used antimicrobial agents, medicinal plant extracts demonstrate considerable potential for clinical use, due primarily to their efficacy allied to relatively low incidence of adverse side-effects. In this context, the present work aimed to develop a unique dual-layer composite material with enhanced antibacterial activity derived from a coating layer of Poly(vinyl alcohol) (PVA) and Chitosan (CS) containing Agrimonia eupatoria L. (AG). This novel material has properties that facilitate it being electrospun above a conventional cotton gauze bandage pre-treated with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical (TEMPO). The produced dual-layer composite material demonstrated features attractive in production of wound dressings, specifically, wettability, porosity, and swelling capacity. Moreover, antibacterial assays showed that AG-incorporated into PVA_CS’s coating layer could effectively inhibit Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) growth. Equally important, the cytotoxic profile of the dual-layer material in normal human dermal fibroblast (NHDF) cells demonstrated biocompatibility. In summary, these data provide initial confidence that the TEMPO-oxidized cotton/PVA_CS dressing material containing AG extract demonstrates adequate mechanical attributes for use as a wound dressing and represents a promising approach to prevention of bacterial wound contamination.     

Poly(DL‐Lactide‐co‐ε‐Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs

Poly(DL‐lactide‐co‐ε‐caprolactone)/poly(acrylic acid) implantable composite reservoirs for cationic drugs are synthesized by sequentially applying photoirradiation and liquid phase inversion. The chemical composition and microstructure of reservoirs are characterized with Fourier transform infrared spectroscopy‐attenuated total reflection (FTIR‐ATR) and scanning electron microscopy (SEM), respectively. Drug loading and release properties are investigated using methylene blue as the drug model. Biocompatibility of reservoirs is examined through a series of in vitro tests and an in vivo experiment of subcutaneous implantation in Dark Agouti rats. Reservoirs show good ion‐exchange capacity, high water content, and fast reversible swelling with retained geometry. Results of drug loading and release reveal excellent loading efficiency and diffusion‐controlled release during 2 weeks. Biocompatibility tests in vitro demonstrate the lack of implant proinflammatory potential and hindered adhesion of L929 cells on the implant surface. Implants exhibit low acute toxicity and elicit a normal acute foreign body reaction that reaches the early stages of fibrous capsule formation after 7 days.     

Synthesis of Degradable Poly[(Ethylene Glycol)‐co‐(Glycolic Acid)] via the Post‐Polymerization Oxyfunctionalization of Poly(Ethylene Glycol)

To enhance the limited degradability of poly(ethylene glycol) (PEG), a straightforward method of synthesizing poly[(ethylene glycol)‐co‐(glycolic acid)] (P(EG‐co‐GA)) via a ruthenium‐catalyzed, post‐polymerization oxyfunctionalization of various PEGs is developed. Using this method, a set of copolymers with GA compositions of up to 8 mol% are prepared with minimal reduction in molecular weight (<10%) when compared to their commercially available starting materials. The P(EG‐co‐GA) copolymers are shown to undergo hydrolysis under mild conditions.

     

Degradable Poly(amidoamine) Hydrogels as Scaffolds for In Vitro Culturing of Peripheral Nervous System Cells

This paper reports on the synthesis and physico‐chemical, mechanical, and biological characterization of two sets of poly(amidoamine) (PAA) hydrogels with potential as scaffolds for in vivo peripheral nerve regeneration. They are obtained by polyaddition of piperazine with N,N′‐methylenebis(acrylamide) or 1,4‐bis(acryloyl)piperazine with 1,2‐diaminoethane as cross‐linking agent and exhibit a combination of relevant properties, such as mechanical strength, biocompatibility, biodegradability, ability to induce adhesion and proliferation of Schwann cells (SCs) preserving their viability. Moreover, the most promising hydrogels, that is those deriving from 1,4‐bis(acryloyl)piperazine, allow the in vitro growth of the sensitive neurons of the dorsal root ganglia, thus getting around a critical point in the design of conduits for nerve regeneration.

     

pH‐Modulating Poly(ethylene glycol)/Alginate Hydrogel Dressings for the Treatment of Chronic Wounds

The development of chronic wounds has been frequently associated with alkaline pH values. The application of pH‐modulating wound dressings can, therefore, be a promising treatment option to promote normal wound healing. This study reports on the development and characterization of acidic hydrogel dressings based on interpenetrating poly(ethylene glycol) diacrylate/acrylic acid/alginate networks. The incorporation of ionizable carboxylic acid groups results in high liquid uptake up to 500%. The combination of two separate polymer networks significantly improves the tensile and compressive stability. In a 2D cell migration assay, the application of hydrogels (0% to 1.5% acrylic acid) results in complete “wound” closure; hydrogels with 0.25% acrylic acid significantly increase the cell migration velocity to 19.8 ± 1.9 µm h⁻¹. The most promising formulation (hydrogels with 0.25% acrylic acid) is tested on 3D human skin constructs, increasing keratinocyte ingrowth into the wound by 164%.

     

Polymer-Supported Poly(Ethylene Glycol) as a Phase-Transfer Catalyst for Cross-Aldol Condensation of Isobutyroaldehyde and Formaldehyde

Immobilized poly(ethylene glycol) (PEG 600-PS) was used as an effective phase-transfer catalyst for the synthesis of hydroxypivaldehyde from isobutyraldehyde (IBA) and formaldehyde in the presence of an inorganic base. Studies on the influence of the parameters on the course of the reaction in a batch reactor showed that the use of the PEG 600-PS catalyst allowed one to obtain HPA with high efficiency (IBA conversion >96%, selectivity >98%) in a relatively short time and under mild conditions (2 h, 40 °C). The developed method enables easy separation of the post-reaction mixture by simple phase separation, and the immobilized catalyst can be separated by filtration and then used five times without a loss in its activity. The high activity and stability of the catalyst was also confirmed in a test carried out in a flow reactor.     

A Study on the Antioxidant Activity of Pyridylselenium Compounds and their Slow Release from Poly(acrylamide) Hydrogels

Abstract

The antioxidant activity of pyridylselenium compounds has been evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and nitric oxide (NO) scavenging methods. Pyridylselenium compounds have shown far superior (100–1000 times) antioxidant property than ebselen. The control release of bis(2-pyridyl) diselenide from poly(acrylamide) hydrogels has been studied in order to evaluate its release mechanism and diffusion coefficient. The later study also demonstrates that the pyridylselenium loading into the polymer matrix increases the magnitude and the rate of the radical scavenging activity of the poly(acrylamide) hydrogels.     

Physical Hydrogels of Poly(vinyl alcohol) with Different Syndiotacticity Prepared in the Presence of Lactosilated Chitosan Derivatives

Poly(vinyl alcohol) (PVA) physical hydrogels were prepared by repeated freeze–thawing cycles using aqueous solutions of two PVA samples having different degrees of syndiotacticity, a‐PVA and s‐PVA with 55% and 61% of syndiotactic diads, respectively. The hydrogels were prepared in the presence of different amounts of lactosilated chitosan derivatives (LC) of different molecular weight. The PVA stereoregularity was found to have a dramatic effect on the amount of PVA incorporated into the hydrogels, leading to remarkable differences in the swelling degree and porosity of a‐PVA and s‐PVA hydrogels. A significant amount of LC was retained in the hydrogels after equilibrium swelling. The swelling of the a‐PVA hydrogels was found to increase significantly by increasing the amount of LC while it was only slightly increased in the case of s‐PVA hydrogels. The amount of LC released after equilibrium swelling was lower when chitosan derivatives with higher molecular weights were used. Increased initial concentrations of LC resulted in much higher porosity of the hydrogels. TGA and DSC studies showed that LC is stabilized by the incorporation in the PVA hydrogels. The melting temperature of the crystalline regions of PVA was not significantly influenced by LC. Conversely, the extension of the crystalline domains increased in the presence of LC. The retention of a chitosan derivative bearing β‐D ‐galactose side chain residues makes these hydrogels potentially useful as scaffolds for hepatocytes culture.

Scanning electron micrographs of PVA‐LC hydrogels: (a) a‐PVA; (b) a‐PVA/LC₁₅₀ 80:20; (c) a‐PVA/LC₁₅₀ 50:50.     

Impact of the Type of Crosslinking Agents on the Properties of Modified Sodium Alginate/Poly(vinyl Alcohol) Hydrogels

Here, we report on studies on the influence of different crosslinking methods (ionic and chemical) on the physicochemical (swelling ability and degradation in simulated body fluids), structural (FT-IR spectra analysis) and morphological (SEM analysis) properties of SA/PVA hydrogels containing active substances of natural origin. First, an aqueous extract of Echinacea purpurea was prepared using a Soxhlet apparatus. Next, a series of modified SA/PVA-based hydrogels were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate (PEGDA, M_n = 700 g/mol) as a crosslinking agent and, additionally, the ionic reaction in the presence of a 5% w/v calcium chloride solution. The compositions of SA/PVA/E. purpurea-based hydrogels contained a polymer of natural origin—sodium alginate (SA, 1.5% solution)—and a synthetic polymer—poly(vinyl alcohol) (PVA, M_n = 72,000 g/mol, 10% solution)—in the ratio 2:1, and different amounts of the aqueous extract of E. purpurea—5, 10, 15 or 20% (v/v). Additionally, the release behavior of echinacoside from the polymeric matrix was evaluated in phosphate-buffered saline (PBS) at 37 °C. The results indicate that the type of the crosslinking method has a direct impact on the release profile. Consequently, it is possible to design a system that delivers an active substance in a way that depends on the application.     

Fabrication of Sulfated Heterosaccharide/Poly (Vinyl Alcohol) Hydrogel Nanocomposite for Application as Wound Healing Dressing

Nowadays, natural polysaccharides-based hydrogels have achieved promising results as dressings to promote skin healing. In the present study, we prepared a novel hydrogel nanocomposite with poly(vinyl alcohol) (PVA) and sulfated heterosaccharide (UF), named UPH. The SEM results showed that the UPH had dense porous structures with a high porosity and a specific surface area. The UPH had a good swelling property, which can effectively adsorb exudate and keep the wound moist. The in vitro experiments results showed that the UPH was non-cytotoxic and could regulate the inflammatory response and promote the migration of fibroblasts significantly. The phenotypic, histochemistry, and Western blot analyses showed UPH treatment accelerated the wound healing and recovery of skin tissue at wound sites in a C57BL/6 mouse model. Furthermore, the UPH could promote the inflammation process to onset earlier and last shorter than that in a normal process. Given its migration-promoting ability and physicochemical properties, the UPH may provide an effective application for the treatment and management of skin wounds.     

Application of Linear and Branched Poly(Ethylene Glycol)‐Poly(Lactide) Block Copolymers for the Preparation of Films and Solution Electrospun Meshes

Poly(ethylene glycol)‐poly(lactide) (PEG‐PLA) block copolymers are processed to solvent cast films and solution electrospun meshes. The effect of polymer composition, architecture, and number of anchoring points for the plasticizer on swelling, degradation, and mechanical properties of these films and meshes is investigated as potential barrier device for the prevention of peritoneal adhesions. As a result, adequate properties are achieved for the massive films with a longer retention of the plasticizer PEG for star‐shaped block copolymers than for the linear triblock copolymers and consequently more endurable mechanical properties during degradation. For electrospun meshes fabricated using the same polymers, similar trends are observed, but with an earlier start of fragmentation and lower tensile strengths. To overcome the poor mechanical strengths and an occurring shrinkage during incubation, which may impair the coverage of the wound, further adaptions of the meshes and the fabrication process are necessary.

     

Immobilization of Xylanase on Poly (Ethylene Glycol) Methyl Ether 5000 and its Self-Extractive Bioconversion for the Production of Xylo-Oligosaccharides

Endo-β-1,4-xylanase derived from Trichoderma reesei was covalently immobilized on poly (ethylene glycol) methyl ether 5000 (mPEG5000), and the resulting immobilized enzyme had a residual activity of 72.4 % with 82.9 % of PEGylated amino groups. Compared with the free enzyme, the immobilized xylanase was stable at pH values in the range of 4.0–6.0 and temperatures in the range of 50–65 °C. A self-extractive bioconversion system composed of immobilized xylanase, mPEG5000, and sodium citrate was used to produce xylo-oligosaccharides and provided a better distribution of the xylo-oligosaccharides than the free enzyme. Furthermore, the immobilized xylanase could be effectively recovered in situ following the hydrolysis reaction.     

The Effect of Betulin Diphosphate in Wound Dressings of Bacterial Cellulose-ZnO NPs on Platelet Aggregation and the Activity of Oxidoreductases Regulated by NAD(P)+/NAD(P)H-Balance in Burns on Rats

The inhibition of platelet aggregation, and the activity of oxidoreductases and microhemocirculation in a burn wound on the treatment of burns with wound dressings based on bacterial nanocellulose (BC)-zinc oxide nanoparticles (ZnO NPs)-betulin diphosphate (BDP) were studied. The control of the treatment by BC-ZnO NPs-BDP on burned rats by the noninvasive DLF method showed an increase in perfusion and the respiratory component in wavelet spectra, characterizing an improvement in oxygen saturation in the wound. The study on the volunteers’ blood found the inhibition of ADP-induced platelet aggregation by 30–90%. Disaggregation depends on the dose under the action of the ionized form of BDP and ZnO NPs-BDP in a phosphate buffer; it was reversible and had two waves. It was shown on rats that the specific activity of LDH_reverse and LDH_direct (control-intact animals) on day 21 of treatment increased by 11–38% and 23%, respectively. The LDH_reverse/LDH_direct ratio increased at BC-ZnO NPs-BDP treatment, which characterizes efficient NAD+ regeneration. AlDH activity increased significantly in the first 10 days by 70–170%, reflecting the effectiveness of the enzyme and NAD+ in utilizing toxic aldehydes at this stage of burn disease. The activities of GR and G6PDH using NADP(H) were increased with BC-ZnO NPs-BDP treatment.