Tough, high conductivity pectin polysaccharide-based hydrogel for strain sensing and real-time information transmission.

Hydrogels from natural polymers are eco-friendly, biocompatible and adjustable for manufacturing wearable sensors. However, it is still challenging to prepare natural polymer hydrogel sensors with excellent properties (e.g., high conductivity). Here, we developed a physically cross-linked, highly conductive and multifunctional hydrogel (named PPTP) to address this challenge. The natural renewable pectin-based PPTP hydrogel is synthesized by introducing tannic acid (TA), calcium chloride (CaCl2), and sodium chloride (NaCl) into the pectin/polyvinyl alcohol (PVA) dual network structure. The hydrogel exhibits excellent characteristics, including unique tensile strength (2.6155 MPa), high electrical conductivity (7 S m-1), and high sensitivity (GF = 3.75). It is also recyclable, further enhancing its eco-friendly nature. The PPTP hydrogel can be used for monitoring human joint activities, as flexible electrodes for monitoring electrocardiogram (ECG) signals, and touchable screen pen for electronic skin. Moreover, when combined with Morse code and wireless Bluetooth technology, PPTP hydrogels can be used for underwater and land information encryption, and decryption. Our unique PPTP hydrogel offers promising opportunities for medical monitoring, information transfer, and human-computer interaction.

Sustained release of valproic acid loaded on chitosan nanoparticles within hybrid of alginate/chitosan hydrogel with/without stem cells in regeneration of spinal cord injury.

Hydrogels have been increasingly applied in tissue regeneration and drug delivery systems (DDS). In this study, the capacity of valproic acid (Val) encapsulated within hybrid of alginate (Alg)-chitosan (Cs) (Alg-Cs) hydrogel containing Cs nanoparticle (Npch) with/without human endometrial stem cells (hEnSC) was initially examined for regeneration of spinal cord injury (SCI). To evaluate the stability of the synthesized hydrogels zeta potential necessary measurements were made. Physicochemically, the developed hydrogels were evaluated using Fourier-transform infrared (FTIR) spectroscopy. The physical properties including degradation rate, swelling ability, and tunability of the synthesized hydrogels were studied. To evaluate the nerve regeneration ability of the synthesized hydrogels, 35 Sprague-Dawley rats were undergone SCI. The spinal cords were exposed using laminectomy in T9-T10 area and the hemi-section SCI model was made. The rats were then randomly divided into 5 groups (n = 7) including, Alg-Cs/Npch, Alg-Cs/Npch/hEnSCs, Alg-Cs/Npch/Val, and Alg-Cs/Npch/hEnScs/Val, and the control groups without any intervention. The FTIR spectra showed band frequencies and assignments of Val, Alg-Cs, and alginate. Nanoparticles were formulated with a mean diameter of 187 and 210 nm, for Val/Alg-Cs and Alg-Cs, respectively. The loading of Val into Alg-Cs led to its reduced size by about 40 nm. The Cs-Npch/Val hydrogels degraded faster than the Alg-Cs-/Npch/Val hydrogel specifically in extended time of incubation. A higher swelling capacity of Alg-Cs/Npch hydrogel, compared to Cs/Npch/Val and Alg-Cs/Npch/Val hydrogels, was found. The Cs-Npch/Val hydrogels degraded faster than Alg-Cs-/Npch/Val hydrogel. The Alg-Cs/Npch/hEnSCs/Val could regenerate the damaged nerve fibers and histologically prevent the SCI-induced vacuolization spaces. The prepared Alg-Cs/Npch/Val could be a suitable polymeric carrier for taurine drugs as bioactive substrate in nerve tissue engineering (NTE) and DDS.

Polysaccharide-based hydrogel with photothermal effect for accelerating wound healing.

Polysaccharide-based hydrogel has excellent biochemical function, abundant sources, good biocompatibility and other advantages, and has a broad application prospect in biomedical fields, especially in the field of wound healing. With its inherent high specificity and low invasive burden, photothermal therapy has shown great application prospect in preventing wound infection and promoting wound healing. Combining polysaccharide-based hydrogel with photothermal therapy (PTT), multifunctional hydrogel with photothermal, bactericidal, anti-inflammatory and tissue regeneration functions can be designed, so as to achieve better therapeutic effect. This review first focuses on the basic principles of hydrogel and PTT, and the types of polysaccharides that can be used to design hydrogels. In addition, according to the different materials that produce photothermal effects, the design considerations of several representative polysaccharide-based hydrogels are emphatically introduced. Finally, the challenges faced by polysaccharide-based hydrogels with photothermal properties are discussed, and the future prospects of this field are put forward.

A multi-crosslinking strategy of organic and inorganic compound bio-adhesive polysaccharide-based hydrogel for wound hemostasis.

Polysaccharides are naturally occurring polymers with exceptional biodegradable and biocompatible qualities that are used as hemostatic agents. In this study, photoinduced CC bond network and dynamic bond network binding was used to give polysaccharide-based hydrogels the requisite mechanical strength and tissue adhesion. The designed hydrogel was composed of modified carboxymethyl chitosan (CMCS-MA) and oxidized dextran (OD), and introduced hydrogen bond network through tannic acid (TA) doping. Halloysite nanotubes (HNTs) were also added, and the effects of various doping amount on the performance of the hydrogel were examined, in order to enhance the hemostatic property of hydrogel. Experiments on vitro degradation and swelling demonstrated the strong structural stability of hydrogels. The hydrogel has improved tissue adhesion strength, with a maximum adhesion strength of 157.9 kPa, and demonstrated improved compressive strength, with a maximum compressive strength of 80.9 kPa. Meanwhile, the hydrogel had a low hemolysis rate and had no inhibition on cell proliferation. The created hydrogel exhibited a significant aggregation effect on platelets and a reduced blood clotting index (BCI). Importantly, the hydrogel can quickly adhere to seal the wound and has good hemostatic effect in vivo. Our work successfully prepared a polysaccharide-based bio-adhesive hydrogel dressing with stable structure, appropriate mechanical strength, and good hemostatic properties.

Environmentally adaptive polysaccharide-based hydrogels and their applications in extreme conditions: A review.

Polysaccharide hydrogels are one of the most promising hydrogel materials due to their inherent characteristics, including biocompatibility, biodegradability, renewability, and easy modification, and their structure and functional designs have been widely researched to adapt to different application scenarios as well as to broaden their application fields. As typical wet-soft materials, the high water content and water-absorbing ability of polysaccharide-based hydrogels (PHs) are conducive to their wide biomedical applications, such as wound healing, tissue repair, and drug delivery. In addition, along with technological progress, PHs have shown potential application prospects in some high-tech fields, including human-computer interaction, intelligent driving, smart dressing, flexible sensors, etc. However, in practical applications, due to the poor ability of PHs to resist freezing below zero, dehydration at high temperature, and acid-base/swelling-induced deformation in a solution environment, they are prone to lose their wet-soft peculiarities, including structural integrity, injectability, flexibility, transparency, conductivity and other inherent characteristics, which greatly limit their high-tech applications. Hence, reducing their freezing point, enhancing their high-temperature dehydration resistance, and improving their extreme solution tolerance are powerful approaches to endow PHs with multienvironmental adaptability, broadening their application areas. This report systematically reviews the study advances of environmentally adaptive polysaccharide-based hydrogels (EAPHs), comprising anti-icing hydrogels, high temperature/dehydration resistant hydrogels, and acid/base/swelling deformation resistant hydrogels in recent years. First, the construction methods of EAPHs are presented, and the mechanisms and properties of freeze-resistant, high temperature/dehydration-resistant, and acid/base/swelling deformation-resistant adaptations are simply demonstrated. Meanwhile, the features of different strategies to prepare EAPHs as well as the strategies of simultaneously attaining multienvironmental adaptability are reviewed. Then, the applications of extreme EAPHs are summarized, and some meaningful works are well introduced. Finally, the issues and future outlooks of PH environment adaptation research are elucidated.

Polysaccharide-based hydrogel promotes skin wound repair and research progress on its repair mechanism.

Polysaccharides, being a natural, active, and biodegradable polymer, have garnered significant attention due to their exceptional properties. These properties make them ideal for creating multifunctional hydrogels that can be used as wound dressings for skin injuries. Polysaccharide hydrogel has the ability to both simulate the natural extracellular matrix, promote cell proliferation, and provide a suitable environment for wound healing while protecting it from bacterial invasion. Polysaccharide hydrogels offer a promising solution for repairing damaged skin. This review provides an overview of the mechanisms involved in skin damage repair and emphasizes the potential of polysaccharide hydrogels in this regard. For different skin injuries, polysaccharide hydrogels can play a role in promoting wound healing. However, we still need to conduct more research on polysaccharide hydrogels to provide more possibilities for skin damage repair.

Polysaccharide-based hydrogel enriched by epidermal growth factor peptide fragment for improving the wound healing process.

Wounds represent a "silent epidemic" in the global population that impact significantly people's quality of life and the economy of societies. Owing to the numerous therapies, the pursuit of a perfect wound dressing with superior performance for treating all sorts of wounds is still underway. Several studies have shown the potential of integrating restorative peptides into the scaffolds as potential therapeutic candidates for wound healing. So far, there is little information about the wound-healing effect of S-acetamidomethyl Cys 20-31-EGF peptide, a main fragment of epidermal growth factor. In this regard, the effectiveness of this peptide in the alginate-gum arabic polysaccharide hydrogel was evaluated as a wound dressing (AG-P). Physicochemical evaluation of the hydrogels demonstrated that the incorporation of the peptide compressed the hydrogel network due to the presence of hydrogen and electrostatic bonds without significant effect on the mechanical, viscoelastic properties, swelling and degradation rate of the hydrogel. The hydrogel could continuously release the peptide and prevent rapid attenuation of its concentration. Cellular assessment of AG-P by scratch test and CFSE cytoplasmic dye/flow cytometry technique encouraged the migration and proliferation of human fibroblast cells, respectively. The effect of the AG-P on the expression of IL-6, TNF-α, NF-kB1 and VEGF genes indicated that this hydrogel reduced inflammation, and significantly increased angiogenesis compared to the control group based on the Real-time PCR results. In vitro assessment indicated that this structure can promote efficient and faster wound regeneration by altering the microenvironment of the wound. The hydrogel showed interesting features to be more equipped with other therapeutic agents making it as suitable dressing for various type of the wounds.

Polysaccharide-based hydrogels containing herbal extracts for wound healing applications.

Development of an ideal wound dressing with effective function for healing various types of wounds is the ultimate desire of the researchers. Natural-based compounds such as polysaccharides and phytochemicals offer useful properties making them perfect candidates for wound management. Polysaccharides-based hydrogels with an interconnected three-dimensional network, and desired properties have great potential as a carrier for delivery of different herbal extracts for oral and topical applications. Herbal extracts are extensively used for wound healing purposes, individually or in combination with other active agents. This study summarizes the current knowledge acquired on the preparation, functionalizing, and application of different kinds of polysaccharide-based hydrogels enriched by herbal extracts for different wound healing applications. The structural, biological, and functional impact of the polysaccharides and herbal extracts on the final hydrogel characteristics, as well as their influence on the different phases of the wound healing process have been discussed.

A stretchable, self-healing, okra polysaccharide-based hydrogel for fast-response and ultra-sensitive strain sensors.

Self-healing conductive hydrogels have attracted widespread attention as a new generation of smart wearable devices and human motion monitoring sensors. To improve the biocompatibility and degradability of such strain sensors, we report a sensor with a sandwich structure based on a biomucopolysaccharide hydrogel. The sensor was constructed with a stretchable self-healing hydrogel composed of polyvinyl alcohol (PVA), okra polysaccharide (OP), borax, and a conductive layer of silver nanowires. The obtained OP/PVA/borax hydrogel exhibited excellent stretchability (~1073.7%) and self-healing ability (93.6% within 5 min), and the resultant hydrogel-based strain sensor demonstrated high sensitivity (gauge factor = 6.34), short response time (~20 ms), and good working stability. This study provides innovative ideas for the development of biopolysaccharide hydrogels for applications in the field of sensors.

Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing.

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

Conducting chitosan/hydroxylethyl cellulose/polyaniline bionanocomposites hydrogel based on graphene oxide doped with Ag-NPs.

The current work focuses on a cheap and simple preparation of highly conducting chitosan/hydroxyl ethylcellulose/polyaniline loaded with graphene oxide doped by silver nanoparticles (CS/HEC/PAni/GO@Ag) bionanocomposite as a biodegradable and biocompatible hydrogel for energy storage technology. Scanning electron microscopy (SEM) displays the compatibility of chitosan, hydroxyl ethyl cellulose, and polyaniline and a good distribution of GO@Ag-NPs in bionanocomposite hydrogels. X-ray diffraction (XRD) displayed the structure and existence of GO@Ag-NPs in the matrix. The swelling percentage and the antibacterial activities slightly increased with raising the content of GO@Ag-NPs. Also, the presence of both chitosan and cellulose improves the biodegradation of the fabricated bionanocomposites, which is increased by adding GO. Moreover, the incorporation of 5% GO@Ag-NPs in hydrogels enhances dc-conductivity by about 25 times from 3.37 × 10-3 to 8.53 × 10-2 S/cm. The fabricated hydrogels are inexpensive, eco-friendly, and have high capacitance and permittivity, and so they can store electrical energy.

Berberine loaded chitosan nanoparticles encapsulated in polysaccharide-based hydrogel for the repair of spinal cord.

The potential of berberine loaded in chitosan nanoparticles (BerNChs) within a hybrid of alginate (Alg) and chitosan (Ch) hydrogel was investigated for the substrate which is known as an inhibit activator proteins. The physicochemical properties of the developed Alg-Ch hydrogel were investigated by fourier-transform infrared spectroscopy. The swelling ability and degradation rate of hydrogels were also analyzed in a phosphate-buffered saline solution at physiological pH. The seeded scaffolds with endometrial stem cells as well as scaffolds alone were then transplanted into hemisected SCI rats. The SEM images displayed the favorable seeding and survival of the cells on the Alg-Ch/BerNChs hydrogel scaffold. The obtained data from immunostining of neuroflilament (NF), as a neuronal growth marker, in the various groups showed that the lowest and highest immunoractivity was belonged to the control and Alg-Ch/BerNCh seeded with ESCs groups, respectively. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions, clinically. The results suggested that combination therapy using the endometrial stem cells seeded on Alg-Ch/BerNChs hydrogel scaffold has the potential to regenerate the injured spinal cord and to limit the secondary damage.

Characterization of encapsulated cells within hyaluronic acid and alginate microcapsules produced via horseradish peroxidase-catalyzed crosslinking.

Hydrogel microcapsules having the ability to promote cell adhesion and proliferation are a useful tool for fabricating tissue in vitro. The present study explored the effects of two anionic polysaccharide hydrogel membranes which have an impact on the adhesiveness, morphology and growth of cells. Microcapsules were made by coating a cell-laden gelatin microparticle with a hydrogel membrane produced from modified hyaluronic acid or alginate possessing phenolic hydroxyl moieties (HA-Ph or Alg-Ph respectively) via a horseradish peroxidase-catalyzed crosslinking reaction. Some gelatin was retained within the microcapsules to support the attachment and growth of encapsulated cells. The morphological and functional characteristics of encapsulated HeLa and 10T1/2 cells were evaluated. The HA-Ph hydrogel, which exhibited greater retention of gelatin, showed a higher degree of cytocompatibility with respect to cell adhesion, spreading and proliferation compared with the Alg-Ph hydrogel membrane. These findings indicate that HA-Ph microcapsules synthesized around a temporary gelatin microparticles are a promising cell vehicle for tissue engineering applications.

Mechanisms of pore formation in hydrogel scaffolds textured by freeze-drying.

Whereas freeze-drying is a widely used method to produce porous hydrogel scaffolds, the mechanisms of pore formation involved in this process remained poorly characterized. To explore this, we focused on a cross-linked polysaccharide-based hydrogel developed for bone tissue engineering. Scaffolds were first swollen in 0.025% NaCl then freeze-dried at low cooling rate, i.e. -0.1 °C min-1, and finally swollen in aqueous solvents of increasing ionic strength. We found that scaffold's porous structure is strongly conditioned by the nucleation of ice. Electron cryo-microscopy of frozen scaffolds demonstrates that each pore results from the growth of one to a few ice grains. Most crystals were formed by secondary nucleation since very few nucleating sites were initially present in each scaffold (0.1 nuclei cm-3 °C-1). The polymer chains are rejected in the intergranular space and form a macro-network. Its characteristic length scale coincides with the ice grain size (160 µm) and is several orders of magnitude greater than the mesh size (90 nm) of the cross-linked network. After sublimation, the ice grains are replaced by macro-pores of 280 µm mean size and the resulting dry structure is highly porous, i.e. 93%, as measured by high-resolution X-ray tomography. In the swollen state, the scaffold mean pore size decreases in aqueous solvent of increasing ionic strength (120 µm in 0.025% NaCl and 54 µm in DBPS) but the porosity remains the same, i.e. 29% regardless of the solvent. Finally, cell seeding of dried scaffolds demonstrates that the pores are adequately interconnected to allow homogenous cell distribution. STATEMENT OF SIGNIFICANCE: The fabrication of hydrogel scaffolds is an important research area in tissue engineering. Hydrogels are textured to provide a 3D-framework that is favorable for cell proliferation and/or differentiation. Optimum hydrogel pore size depends on its biological application. Producing porous hydrogels is commonly achieved through freeze-drying. However, the mechanisms of pore formation remain to be fully understood. We carefully analyzed scaffolds of a cross-linked polysaccharide-based hydrogel developed for bone tissue engineering, using state-of-the-art microscopic techniques. Our experimental results evidenced the shaping of hydrogel during the freezing step, through a specific ice-templating mechanism. These findings will guide the strategies for controlling the porous structure of hydrogel scaffolds.