Polysaccharide Hydrogels Research Articles

Photo-responsive supramolecular hyaluronic acid hydrogels for accelerated wound healing

Supramolecular hydrogels confer control over structural properties in a reversible, dynamic, and biomimetic fashion. The design of supramolecular hydrogels with an improved structural and functional recapitulation of damaged organs is important for clinical applications. For wound healing management, in particular, an effective healing process, through the modulation of epidermal growth factor (EGF) delivery using supramolecular polysaccharide hydrogels, has yet to be developed. In this study, photo-responsive supramolecular polysaccharide hydrogels were formed through host-guest interactions between azobenzene and β-cyclodextrin groups conjugated to hyaluronic acid chains. By exploiting the photoisomerization properties of azobenzene under different wavelengths, a supramolecular hydrogel featuring a dynamic spatial network crosslink density through the application of a light stimulus was obtained. Under ultra violet (UV) light, the loosened hydrogel can rapidly release EGF, thereby enhancing EGF delivery at the wound site. Based on an in vivo assessment of the healing process through a full-thickness skin defect model, the controlled EGF release from a supramolecular hydrogel exhibited superior wound healing efficiency with respect to granulation tissue formation, growth factor levels, and angiogenesis. Therefore, the proposed supramolecular hydrogels are potentially valuable as controlled delivery systems for future clinical wound healing applications.

Carboxymethylchitosan hydrogel manufactured by radiation-induced crosslinking as potential nerve regeneration guide scaffold

The main objective of the work was to elaborate a methodology of manufacturing tubular guide with an internal scaffold of polysaccharide hydrogel towards potential application for supporting peripheral nerve regeneration. Carboxymethylchitosan (CMSC), a derivative of chitosan and a prospective material in the medical field, was examined with respect to degradation and crosslinking processes and eventually converted into a hydrogel through radiation-induced crosslinking. Physico-chemical properties of the degraded and crosslinked CMCS materials were evaluated by viscometry, UV–Vis, FTIR, TGA, XRD and SEM. Biological characterization of CMCS gels was done with XTT method for potential cytotoxicity and by preliminary in vivo examination using a rat model, to assess local reaction after implantation. Additionally, an antimicrobial potential of the CMCS materials was examined with bacterial suspension and agar diffusion methods using Gram-positive and -negative strains. The positive results of the abovementioned evaluations, after taking under account sorption characteristics of the gels, allowed to consider 12% CMCS aqueous solutions irradiated with an electron-beam dose of 25 kGy as a suitable material for internal filling of biodegradable tubes made of poly(L-lactic acid) and poly(trimethylene carbonate) blend biomaterial. The radiation processing of CMCS resulted in an in situ synthesis of a soft scaffold inside the tube, and simultaneous sterilization of the entire medical implant. Lack of toxicity of the gel and antimicrobial activity of CMCS against E. coli strain combined with hydrophilic properties make the hydrogel a potential material for supporting peripheral nerveregeneration guides.

Optimization of human-like collagen composite polysaccharide hydrogel dressing preparation using response surface for burn repair

Collagen and polysaccharide materials have great advantages for burn wound healing and skin regeneration. The purpose of this study was to develop a promising burn dressing. Mixing hyaluronic acid (HA), carboxylated chitosan (CCS) and human-like collagen (HLC) to simulate extracellular matrix (ECM), and glutamine transaminase (TG) was used as a crosslinker. The mechanical properties and pore size of the hydrogel were optimized by response surface methodology. The results showed that the tensile elastic modulus of the hydrogel was 480.43 ± 15.82 kPa, the tensile strain was 55.23 ± 2.43 %, and the pore size was 90.43 ± 5.57 μm. This study constructed a skin burn model and demonstrated that the hydrogel dressing could effectively prevent bacteria infection and confirmed that the hydrogel dressing was more beneficial for promoting burn wound healing than a commercial film (DUO DERM). Therefore, the HLC/HA/CCS hydrogel can be considered a promising burn wound dressing.

Polysaccharide Hydrogel and its Application Analysis

Polysaccharide Hydrogel and its Application Analysis

Enhancement of Biomimetic Enzymatic Mineralization of Gellan Gum Polysaccharide Hydrogels by Plant-Derived Gallotannins.

Mineralization of hydrogel biomaterials with calcium phosphate (CaP) is considered advantageous for bone regeneration. Mineralization can be both induced by the enzyme alkaline phosphatase (ALP) and promoted by calcium-binding biomolecules, such as plant-derived polyphenols. In this study, ALP-loaded gellan gum (GG) hydrogels were enriched with gallotannins, a subclass of polyphenols. Five preparations were compared, namely three tannic acids of differing molecular weight (MW), pentagalloyl glucose (PGG), and a gallotannin-rich extract from mango kernel (Mangifera indica L.). Certain gallotannin preparations promoted mineralization to a greater degree than others. The various gallotannin preparations bound differently to ALP and influenced the size of aggregates of ALP, which may be related to ability to promote mineralization. Human osteoblast-like Saos-2 cells grew in eluate from mineralized hydrogels. Gallotannin incorporation impeded cell growth on hydrogels and did not impart antibacterial activity. In conclusion, gallotannin incorporation aided mineralization but reduced cytocompatibility.

Sustainable, flexible and biocompatible hydrogels derived from microbial polysaccharides with tailorable structures for tissue engineering

Polysaccharides derived from microorganisms have received considerable attention in designing hydrogel materials. However, most microbial polysaccharide-constructed hydrogels evaluated in preclinical trials are not favorable candidates for biomedical applications owing to concerns regarding poor mechanical strength and complicated fabrication process. Herein, we describe a new polysaccharide hydrogel scaffold containing salecan together with gellan gum network as the polymeric matrix. Properly controlling the physical and chemical properties including swelling, water release, thermal stability, viscoelasticity and morphology of the resulting gel are easily achieved by simply changing the salecan/gellan gum ratios. Notably, these salecan/gellan gum scaffolds friendly support cell survival and proliferation. More significantly, we have systematically evaluated these developed hydrogels for the biocompatible experiments in vitro and in vivo and results indicated the products are non-toxic. Taken together, such hydrogels derived from microbial polysaccharides and readily synthesized through a one-step mixing protocol have translational potentials in the clinic serving as cell devices for tissue engineering.

Fabrication of CeO2 nanoparticles embedded in polysaccharide hydrogel and their application in skin wound healing

Fabrication of CeO2 nanoparticles embedded in polysaccharide hydrogel and their application in skin wound healing

Thermosensitive and pH-responsive tannin-containing hydroxypropyl chitin hydrogel with long-lasting antibacterial activity for wound healing

Polysaccharide hydrogels have been widely used as wound dressings because of their biocompatibility and ability to provide moist environment for wound healing. However, bacterial infection often delays the healing process. Herein, a novel thermosensitive and pH-sensitive hydroxypropyl chitin/tannic acid/ferric ion (HPCH/TA/Fe) composite hydrogel was fabricated by a simple assembly. The pre-cooled hydrogel precursor solution can be injected onto the irregular wound area and gel rapidly at physiological temperature. The TA not only acted as a crosslinker to enhance mechanical properties of the hydrogel, but also as an antibacterial agent which could be sustainably released in response to the acidic environment. The composite hydrogel showed excellent broad-spectrum antibacterial activity up to 7 days with negligible cytotoxicity. Moreover, the hydrogel can inhibit bacterial infection and accelerate the wound healing process without scars in the mouse experiment. These results indicate the potential application of this composite hydrogel for the infected wound healing.

A fast and dual crosslinking hydrogel based on vinyl ether sodium alginate

Optimal modification and gelation strategies of polysaccharide hydrogels have been developed for biomedical applications. Herein, a kind of fast crosslinking alginate hydrogel with superior gel properties was prepared for the first time combining dual crosslinking mechanisms. Firstly, sodium alginate (SA) was modified by vinyl ether side chains through one-step amidation reaction with aminopropyl vinyl ether (APVE) catalyzed by EDC/NHS. Just within 10 s, the grafting product of SA-VE was demonstrated to form hydrogen bonded hydrogel SA-VE/H2O spontaneously. Based on this mechanism, a dual crosslinking alginate hydrogel SA-VE/DTT was fabricated through introducing thiol-ene click chemistry reaction with dithiothreitol (DTT) under UV exposure. According to rheological results, the photo-crosslinking process was completed within 5–9 min. Combining hydrogen bonding and thiol-ene click chemistry, the dual crosslinking mechanism was proved to bring the hydrogel system not only fast gelation but also superior storage modulus up to 13373 Pa and excellent stability of over 1 month. All the hydrogels exhibited non-cytotoxicity towards NIH-3T3 fibroblasts. Furthermore, the 26 s rapid hemostasis behavior of SA-VE exhibited in rat tail hemostasis experiment reveals its potential application in wound dressing materials.

Biocompatible Hydrogels Based on Food Gums with Tunable Physicochemical Properties as Scaffolds for Cell Culture.

Hydrogels composed of food gums have gained attention for future biomedical applications, such as targeted delivery and tissue engineering. For their translation to clinical utilization, reliable biocompatibility, sufficient mechanical performance, and tunable structure of polysaccharide hydrogels are required aspects. In this work, we report a unique hybrid polysaccharide hydrogel composed of salecan and curdlan, in which the former is a thickening agent and the latter serves as a network matrix. The physicochemical properties, such as mechanical strength, thermal stability, swelling, and morphology, of the developed composite hydrogel can be accurately modulated by varying the polysaccharide content. Importantly, cytotoxicity assays show the non-toxicity of this hybrid hydrogel. Furthermore, this hydrogel system can support cell proliferation, migration, and function. Altogether, our work proposes a new strategy to build a polysaccharide-constructed hydrogel scaffold, which holds much promise for tissue engineering in terms of cell engraftment, survival, proliferation, and function.

From kPa to MPa: An Environmentally Friendly Way to Prepare a Polysaccharide Hydrogel with Tunable Mechanical Properties

Polysaccharide hydrogels possess weak mechanical properties because of their high water content. Herein, a simple, facile, and green method for preparing a polysaccharide hydrogel spanning a 100-fo...

Macroporous Hydrogel Scaffolds with Tunable Physicochemical Properties for Tissue Engineering Constructed Using Renewable Polysaccharides.

Polysaccharides have recently attracted increasing attention in the construction of hydrogel devices for biomedical applications. However, polysaccharide-based hydrogels are not suitable for most preclinical applications because of their limited mechanical properties and poor tunability. In this study, we employed a simple and eco-friendly approach to producing a macroporous polysaccharide hydrogel composed of salecan and κ-carrageenan without the use of toxic chemicals. We evaluated the physicochemical properties of the obtained salecan/κ-carrageenan hydrogel and found that its viscoelasticity, morphology, swelling, and thermal stability could be simply controlled by changing the polysaccharide dose in the pre-gel solution. The co-incubation of the fabricated hydrogel with mouse fibroblast cells demonstrated that the hydrogel can support cell adhesion, migration, and growth. Moreover, the hydrogel exhibited good biocompatibility in vivo. Overall, the findings provide a new strategy for the fabrication and optimization of polysaccharide-based hydrogel scaffolds for application in tissue engineering.

Chitosan/Ulva lactuca polysaccharide hydrogel containing copper (ii) beneficial for biofilm-associated wound infection: Formulation characterizations and In vitro study

The present investigation elaborates the energy efficient synthesis of chitosan/Ulva lactuca polysaccharide hydrogel impregnated with copper (II) (Cu-CS/ULP) for wound dressing applications. We successfully characterized the prepared hydrogel using FTIR, SEM, TG-DTA and swelling analysis. Compare to chitosan/U.lactuca polysaccharide hydrogel (CS/ULP), the Cu-CS/ULP hydrogel show a similar framework with the best mechanical properties. The whole blood clotting examination shows that the copper (II) can expand the blood clotting rates of the CS/ULP hydrogel. Free radical scavenging activity and prevention of protein degradation confirmed by DPPH and protein degradation assays. The released copper (II) from Cu-CS/ULP hydrogel exhibited a strong antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumoniae) and Gram-positive (Bacillus subtilis and Staphylococcus aureus). Cu-CS/ULP hydrogel showed a significant activity in biofilm inhibition mass compared to that of CS/ULP. The present suggested that the copper (II) loaded CS/ULP hydrogel is a promising biomaterial for wound dressing application.

Enhanced osseointegration of three-dimensional supramolecular bioactive interface through osteoporotic microenvironment regulation.

Purpose: Osteoporosis is more likely to cause serious complications after joint replacement, mainly due to physiological defects of endogenous osteogenic cells and the pathological osteoclast activity. It is a feasible solution to design a prosthetic surface interface that specifically addresses this troublesome situation.Methods: A novel “three-dimensional (3D) inorganic-organic supramolecular bioactive interface” was constructed consisting of stiff 3D printing porous metal scaffold and soft multifunctional, self-healable, injectable, and biodegradable supramolecular polysaccharide hydrogel. Apart from mimicking the bone extracellular matrix, the bioactive interface could also encapsulate bioactive substances, namely bone marrow mesenchymal stem cells (BMSCs) and bone morphogenetic protein-2 (BMP-2). A series of in vitro characterizations, such as topography and mechanical characterization, in vitro release of BMP-2, biocompatibility analysis, and osteogenic induction of BMSCs were carried out. After that, the in vivo osseointegration effect of the bioactive interface was investigated in detail using an osteoporotic model.Results: The administration of injectable supramolecular hydrogel into the inner pores of 3D printing porous metal scaffold could obviously change the morphology of BMSCs and facilitate its cell proliferation. Meanwhile, BMP-2 was capable of being sustained released from supramolecular hydrogel, and subsequently induced osteogenic differentiation of BMSCs and promoted the integration of the metal microspores-bone interface in vitro and in vivo. Moreover, the osteoporosis condition of bone around the bioactive interface was significantly ameliorated.Conclusion: This study demonstrates that the 3D inorganic-organic supramolecular bioactive interface can serve as a novel artificial prosthesis interface for various osteogenesis-deficient patients, such as osteoporosis and rheumatoid arthritis.

Tuning the strength and swelling of an injectable polysaccharide hydrogel and the subsequent release of a broad spectrum bacteriocin, nisin A

Bacteriocins, which are antimicrobial peptides, are a potential alternative to current ineffective antimicrobial therapies. They can inhibit the growth of clinically relevant pathogens but their proteinaceous nature renders them susceptible to degradation and deactivation in vivo. We have designed injectable polysaccharide hydrogels for the controlled release of an incorporated bacteriocin, nisin. Nisin was encapsulated into these hydrogels which were composed of varying percentages of oxidised dextran, alginate functionalised with hydrazine groups and glycol chitosan. The nisin gels exhibited antimicrobial activity against Staphylococcus aureus up to 10 days. The incorporation of a deacetylated chitosan and the reduction of alginate-hydrazine could be used to tune the gel's swelling behaviour, strength and the subsequent release profile of nisin. Glycol chitosan also shows synergistic inhibition of S. aureus with nisin.

Impact of metal ions on structural EPS hydrogels from aerobic granular sludge

Structural extracellular polymeric substances (structural EPS) can form stable hydrogels and are considered to be responsible for the stability of biofilms and aerobic granular sludge. Structural EPS were extracted from aerobic granular sludge and characterized for their gel-forming capacity with different alkaline earth and transition metal ions. The structural EPS hydrogels were compared to alginate hydrogels. Alginate is a well characterized polymer which is able to form stiff hydrogels with multivalent ions. The stiffness of the obtained hydrogels was measured with dynamic mechanical analysis and quantified by the Young’s modulus. Furthermore the stability of structural EPS hydrogels towards disintegration in the presence of ethylenediaminetetraacetic acid (EDTA) was evaluated at pH 4.5–10.5 and compared to that of alginate, polygalacturonic acid and κ-carrageenan. The stiffness of alginate hydrogels was multiple times higher than that of structural EPS. Alkaline earth metals resulted in stiffer alginate hydrogels than transition metals. For structural EPS this trend was opposite to alginate. Independent of the pH, polysaccharide hydrogels were quickly disintegrated when being exposed to EDTA. Structural EPS hydrogels demonstrated greater stability towards EDTA and were still intact after one month at pH 4.5–8.5. It is suggested that the gelling mechanism of structural EPS is not only related to metal ion complexation of the polymers, but to a combination of interactions of multiple functional groups present in structural EPS. This study helps to further understand and characterize structural EPS from aerobic granular sludge, and therewith understand its stability and that of biofilms in general.

Stimuli-Responsive Polysaccharide Hydrogels for Biomedical Applications: a Review

This review aims to present methods for obtaining polysaccharide hydrogels, their properties and sensitivity to environmental stimuli, as well as their potential applications in biomedicine. Living systems respond to external stimuli by adapting themselves to changing conditions. Hydrogels are a class of materials with 3D networks of polymers that can absorb high amounts of water or biological fluids while remaining insoluble under physiological conditions compared with general absorbent materials, with their characteristic being dependent on network structure and the external environment. Stimuli-responsive hydrogels have the ability to respond to changes in their external environment. They can exhibit dramatic changes in their swelling behavior, network structure, permeability, and mechanical strength in response to variations in temperature, pH, glucose, electric field, light, etc. However, such changes are reversible; therefore, hydrogels can convert to their initial state as soon as the trigger is removed. Because of compatibility with living tissues, hydrogels can be used in different biomedical purposes. The application of stimuli-responsive polysaccharide hydrogels in the biomedical field has become increasingly popular with many research groups and industries. In addition to their ability to undergo large reversible transitions in their swelling behavior due to small physiological or environmental changes, they are also often highly biocompatible and versatile and possess a high storage capacity for the immobilization of biomolecules.

Injectable Hydrogel Combined with Nucleus Pulposus-Derived Mesenchymal Stem Cells for the Treatment of Degenerative Intervertebral Disc in Rats.

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83 ± 227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.

Semi-interpenetrating nanosilver doped polysaccharide hydrogel scaffolds for cutaneous wound healing

The extensive advancement with novel wound dressing materials functionalized with desirable properties, often touted as a panacea for cuts and burns afflicting various pathologies. However, it would indeed be a hard task to isolate any such material which perfectly fits the needs of any biomedical issue at hand. Biocompatibility, biodegradability as well as non-toxicity of natural polysaccharide served as a versatile and tunable platform for designing natural polysaccharide based scaffolds as an attractive tool in tissue engineering with a greater degree of acceptability. In this regard, we aimed to fabricate a semi interpenetrating hydrogel via exploiting the nontoxic and immune-stimulatory nature of galacto-xyloglucan (PST001) which was further doped with silver nanoparticles to formulate SNP@PST. The wound healing potential of SNP@PST was then studied both with in vitro and preclinical mice models. The current study gives a formulation for cost effective preparation of polysaccharide hydrogels using acrylamide crosslinking with improved biocompatibility and degradability. Wound healing studies in mice proved the efficiency of gels for the clinical application wherein the incorporation of nanosilver greatly enhanced the antimicrobial activity.

Probing Surface Hydration and Molecular Structure of Zwitterionic and Polyacrylamide Hydrogels.

A hydrogel is a hydrophilic cross-linked polymer network which can contain a large amount of water. Hydrogels with distinguished interfacial physical toughness were analyzed for their potential application as antifouling coating materials, utilizing sum frequency generation (SFG) spectroscopy as the interfacial analytical technique. The surface structures of one sulfobetaine (SBMA) zwitterionic hydrogel (ZWHG) and two polysaccharide hydrogels (PHGs) were probed in air; their interfacial structures with silica were examined using SFG in water and protein solutions, respectively. Both ZWHG and PHGs interfaces in water were dominated by strongly hydrogen-bonded water molecules, but the bonding strength associated with ZWHG was much stronger. Although all hydrogels experienced interfacial change in the presence of protein solutions, after cleaning, the zwitterionic hydrogel interface recovered almost completely while the other two hydrogels were subject to irreversible protein adsorption. Additionally, orientational analysis of ZWHG methyl groups in water was conducted and related to the superior hydrogen-bonding strength of water molecules at the ZWHG interface. The interfacial structures of hydrogel materials probed by SFG can be correlated to their antifouling properties. This research highlighted the critical role that hydrogen-bonding strength of interfacial water molecules play for antifouling applications.