Hemocompatibility of Ca2+‐Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis

The present work investigates Ca²⁺‐crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood‐derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet‐free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.     

A Shear-Thinning,Self-Healing,Dual-Cross Linked Hydrogel Based on Gelatin/Vanillin/Fe3+/AGP-AgNPs: Synthesis,Antibacterial, and Wound-Healing Assessment

A shear-thinning and self-healing hydrogel based on a gelatin biopolymer is synthesized using vanillin and Fe³⁺ as dual crosslinking agents. Rheological studies indicate the formation of a strong gel found to be injectable and exhibit rapid self-healing (within 10 min). The hydrogels also exhibited a high degree of swelling, suggesting potential as wound dressings since the absorption of large amounts of wound exudate, and optimum moisture levels, lead to accelerated wound healing. Andrographolide, an anti-inflammatory natural product is used to fabricate silver nanoparticles, which are characterized and composited with the fabricated hydrogels to imbue them with anti-microbial activity. The nanoparticle/hydrogel composites exhibit activity against Escherichia coli, Staphylococcus aureus, and Burkholderia pseudomallei, the pathogen that causes melioidosis, a serious but neglected disease affecting southeast Asia and northern Australia. Finally, the nanoparticle/hydrogel composites are shown to enhance wound closure in animal models compared to the hydrogel alone, confirming that these hydrogel composites hold great potential in the biomedical field.     

Injectable and self-healing hydrogels with tissue adhesiveness and antibacterial activity as wound dressings for infected wound healing

The design of wound dressings with excellent self-healing ability, adequate adhesion, good biocompatibility, and potential antibacterial ability is of great significance for the healing of infected wounds arising from human activities. Herein, a series of multi-functional hydrogel dressings, poly(ionized isocyanoethyl methacrylate-glutamine)/poly(hexamethylene guanidine) (iG_x/PHMG_y) hydrogels, were obtained through homopolymerization of fully ionized isocyanoethyl methacrylate-glutamine (iIEM-Gln) in the presence of poly(hexamethylene guanidine) (PHMG), in which strong hydrogen bonds were formed among urea groups in the P (iIEM-Gln) chain to form a stable hydrogel network. The prepared iG_x/PHMG_y hydrogels exhibited adequate self-healing ability and tissue adhesion, which could be firmly adhered to the wound surface and remained intact during application. In addition, the presence of PHMG imparted good antibacterial activity to the hydrogels for the effective promotion of the wound healing in S. aureus infected skin wound on mice. Overall, this multi-functional hydrogel provides a facile and effective strategy for the design of infected wound dressings, and may show great potential in clinical applications.     

A Spray‐Filming Self‐Healing Hydrogel Fabricated from Modified Sodium Alginate and Gelatin as a Bacterial Barrier

Self‐healing hydrogels as wound dressings still face challenges in infection prevention, especially in the dressing of mass wounds, due to their inflexibility and the slow formation of the protective film on the wound. Therefore, designing a spray‐filming (rapid‐forming) hydrogel that can serve as a bacterial barrier is of particular significance in the development of wound dressings. Here, a self‐healing hydrogel based on adipic acid dihydrazide‐modified gelatin (Gel‐ADH) and monoaldehyde‐modified sodium alginate(SA‐mCHO) is prepared. Using dynamic, Schiff base bonds, the hydrogels exhibit excellent self‐healing properties. Moreover, the gelation time of SA‐mCHO/Gel‐ADH (SG) hydrogels is shortened to 2–21 s, resulting in rapid filming by spraying the two precursor solutions. In addition, the rapid spray‐filming ability might offer sufficient flexibility and rapidity for dealing with mass and irregular wounds. Notably, the bacterial barrier experiments show that the SG hydrogel films could form an effective barrier to Staphylococcus aureus and Candida albicans for 12 h. Therefore, SG hydrogels could be used in wound dressings and they show great promise in applications associated with mass and irregular traumas.     

Sponge-inspired multisensory hydrogel

The preparation of smart sensors with multiple sensory systems, reusable property, and high sensitivity remains a challenge. Here, inspired by a sponge, we develop a multisensory PCA–poly(vinyl alcohol) (PVA)/borax–LiCl hydrogel (named PPL hydrogel) with low cost and simple fabrication process using sodium polyacrylate (PAAS), PVA, and lithium chloride (LiCl) to address this challenge. PPL hydrogel has a sponge-like porous structure and can repeatedly “absorb” and “drain” water, while maintaining good tensile (strain up to 1442%) and electrical conductivity. PAAS builds the main skeleton of PPL hydrogels and provides the basis for building the pore structure, PVA enhances the mechanical properties of the crosslinked network, while LiCl ionic solution further improves the conductivity, which can reach 8.8 s m⁻¹ and be increased nearly 42 times better than without LiCl. Therefore, this makes PPL hydrogel a very sensitive sensing system for wearable devices that can be used to detect signals from the human body. Additionally, PPL hydrogel is also capable of detecting temperature due to its temperature-sensitive properties. Moreover, PPL hydrogel can also roughly identify the basic properties of different solvents. Our simple, low-cost and multisensory PPL hydrogel offers promising opportunities for multisensory sensors, even functional/smart materials, flexible/wearable devices, and medical care.     

Effect of Amino Acid Types on the Mechanical and Antimicrobial Properties of Amino Acid-Based Polyionic Liquid Hydrogels

Polyionic liquid hydrogels attract increasing attention due to their unique properties and potential applications. However, research on amino acid-based polyionic liquid hydrogels is still in its infancy stage. Moreover, the effect of amino acid types on the properties of hydrogels is rarely studied to date. In this work, amino acid-based polyionic liquid hydrogels (D/L-PCAA hydrogels) are synthesized by copolymerizing vinyl choline–amino acid ionic liquids and acrylic acids using Al³⁺ as a crosslinking agent and bacterial cellulose (BC) as a reinforcing agent. The effects of amino acid types on mechanical and antimicrobial properties are systematically investigated. D-arginine-based hydrogel (D-PCArg) shows the highest tensile strength (220.7 KPa), D-phenylalanine-based hydrogel (D-PCPhe) exhibits the highest elongation at break (1346%), and L-aspartic acid-based hydrogel (L-PCAsp) has the highest elastic modulus (206.9 KPa) and toughness (1.74 MJ m⁻³). D/L-PCAsp hydrogels demonstrate stronger antibacterial capacity against Escherichia coli and Staphylococcus aureus, and D/L-PCPhe hydrogels possess higher antifungal activity against Cryptococcus neoformans. Moreover, the resultant hydrogels exhibit prominent hemocompatibility and low toxicity, as well as excellent self-healing capabilities (86%) and conductivity (2.8 S m⁻¹). These results indicate that D/L-PCAA hydrogel provides a promise for applications in wound dressings.     

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

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%.

     

Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca²⁺, and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.     

Dehydration kinetics of polyvinyl alcohol hydrogel wound dressings during wound healing process

<正>The hydrogel wound dressing based on polyvinyl alcohol(PVA) was prepared by the freezing-thawing cyclic method.The dehydration kinetics of prepared hydrogels was determined using the experimental method and mathematical modeling based on diffusion mechanism.The results show that the dehydration rate of PVA hydrogel wound dressing inversely depends on the hydrogel thickness as well as water content of the wound.On the other hand,the initial water content of hydrogel and the atmospheric humidity have little direct effect on the dehydration rate.The good agreement between experimental and mathematical modeling results in early stages of dehydration process shows that the predominate factor determining the dehydration of these wound dressings is diffusion.     

可注射水凝胶在伤口敷料中的研究进展

目前,在伤口治疗中对伤口敷料的选择越来越严格。传统的伤口敷料如纱布、绷带、海绵等在伤口愈合过程中容易诱发细菌感染,延缓伤口愈合,甚至引发慢性并发症。可注射水凝胶具备良好的生物相容性,能够适应伤口的形状以填充伤口,且具备一定的抗菌活性,从而避免伤口感染,相比传统的水凝胶伤口敷料更具备医疗优势,因此在生物医药领域得到广泛关注。本文对天然型可注射水凝胶和复合型可注射水凝胶在伤口愈合中的研究进展进行了综述;也对可注射水凝胶的未来发展趋势进行了展望。     

Fine-Tuning the Endcap Chemistry of Acrylated Poly(Ethylene Glycol)-Based Hydrogels for Efficient Burn Wound Exudate Management

Most commercial dressings with moderate to high exudate uptake capacities are mechanically weaker and/or require a secondary dressing. The current research article focuses on the development of hydrogel-based wound dressings combining mechanical strength with high exudate absorption capacities using acrylate-endcapped urethane-based precursors (AUPs). AUPs with varying poly(ethylene glycol) backbone molar masses (10 and 20 kg mol⁻¹) and endcap chemistries are successfully synthesized in toluene, subsequently processed into UV-cured hydrogel sheets and are benchmarked against several commercial wound dressings (Hydrosorb, Kaltostat, and Mepilex Ag). The AUP materials show high gel fractions (>90%) together with strong swelling degrees in water, phosphate buffered saline and simulated wound fluid (12.7–19.6 g g⁻¹), as well as tunable mechanical properties (e.g., Young's modulus: 0.026–0.061 MPa). The AUPs have significantly (p < 0.05) higher swelling degrees than the tested commercial dressings, while also being mechanically resistant. The elasticity of the synthesized materials leads to an increased resistance against fatigue. The di- and hexa-acrylated AUPs show excellent in vitro biocompatibility against human foreskin fibroblasts, as evidenced by indirect MTS assays and live/dead cell assays. In conclusion, the processed AUP materials demonstrate high potential for wound healing application and can even compete with commercially available dressings.     

Natural okra-based hydrogel for chronic diabetic wound healing

As a representative of chronic wounds, the long-term high levels of oxidative stress and blood sugar in chronic diabetic wounds lead to serious complications, making them the biggest challenge in the research on wound healing. Many edible natural biomaterials rich in terpenes, phenols, and flavonoids can act as efficient antioxidants. In this study, okra extract was selected as the main component of a wound dressing. The okra extracts obtained via different methods comprehensively maintained the bioactivity of multiple molecules. The robust antioxidant properties of okra significantly reduced intracellular reactive oxygen species production, thereby accelerating the wound healing process. The results showed that okra extracts and their hydrogel dressings increased cell migration, angiogenesis, and re-epithelization of the chronic wound area, considerably promoting wound remodeling in diabetic rats. Therefore, okra-based hydrogels are promising candidates for skin regeneration and wider tissue engineering applications.     

Irradiation of Crosslinked, Poly(Vinyl Alcohol) Blended Hydrogel for Wound Dressing

In order to obtain a more ideal hydrogel wound dressing, crosslinked hydrogel films blended with polyvinyl alcohol (PVA), polyvinyl pyrrolidone, kappa-carrageenan (KC), and powder silk were prepared by electron beam, and their physiochemical properties were investigated as a combination of function factors. The experimental results showed that the gel fraction of the hydrogel films depended mainly on irradiation dose and the monomer concentration of the polymers, the properties of hydrogel could be greatly extended or improved by blending homopolymers. The rate of gel formation of the hydrogel was raised, and the water evaporation from hydrogel could be retarded after mixing with KC, while the tensile strength of hydrogel films were obviously increased after mixing with silk. Toxicity and healing effect of PVA/PVP/KC/silk blended hydrogel films as wound dressings were evaluated. The irradiated blended hydrogel showed satisfactory properties for wound dressing, the hydrogel did not induceany acute general toxic effects, and it is effective for fast healing of wound.     

Hydrogels of chemically cross-linked and organ-metallic complexed interpenetrating PEG networks

The aim of the present work was to prepare a well-defined hydrogel of chemically cross-linked and organ-metallic complexed interpenetrating PEG networks. The hydrogel was synthesized via the reaction of copper(I)- catalyzed 1,3-dipolar azide-alkyne cycloaddition(CuA AC) with poly(ethylene glycol)-dopamine(PEG-DA)("Click Chemistry") followed by complexation with Fe~(3+) ions to crosslink the polymeric network. The chemical composition and morphology of the resulting hydrogels were characterized by Fourier transform infrared spectroscopy(FTIR), ~1H-NMR and scanning electron microscopy(SEM). Swelling ratio, mechanical strength, conductivity, and degradation behaviors of the hydrogels were also studied. The effect of the polymer chain length on properties of hydrogels was explored. The compressive strength of hydrogels could reach as high as 13.1 MPa with a conductivity of 2.2 × 10~(-5) S·cm~(-1). The hydrogels also exhibited excellent thermal stability even at a temperature of 300 °C, whereas degradation of the hydrogel after 7 weeks was observed under a physiological condition. In addition, the hydrogel exhibited a good biocompatibility based on its in vivo performance through an in vivo subcutaneous implantation model. No inflammation and no obvious abnormality of the surrounding tissue were observed when the hydrogel was subcutaneously implanted for 2 weeks. This work is a step towards creating a new pathway to synthesize hydrogels of interpenetrating networks which could be of important applications in the future research.     

Influence of hydration and crosslinking in transdermal delivery of nicotine from chitosan-based gels by thermal analysis

Chitosan is a biopolymer that forms hydrogels after swell in acid medium. The environment of the three-dimensional network of the chitosan-based hydrogels can be modified by its degree of swelling and crosslinking. In this way, nicotine was incorporated in the hydrogel formulations, with or without crosslinking with glutaraldehyde (0.01%), in different swollen states. Transdermal delivery of nicotine by chitosan-based hydrogels was studied in order to achieve the prolonged administration of the drug. Thermal analysis indicated a preliminary stability of these formulations, and the mechanism of drug release from hydrogels was dependent of the swelling degree and crosslinking. These formulations were able to control the transdermal flux of nicotine for up to 48 h following zero-order kinetics. The hydrogels with higher amounts of water or the partially dried crosslinked hydrogels reduced the partition of nicotine into the skin, leading to a minor transdermal flux of the drug (<3.4 µg cm⁻² h⁻¹). On the other hand, the partially dried non-crosslinked hydrogels lead to a major transdermal flux of the drug (20.19 µg cm⁻² h⁻¹) due to modifications of the environment into the hydrogel. In this way, these transdermal formulations were promising vehicles for prolonged administration of nicotine.

     

Injectable baicalin/F127 hydrogel with antioxidant activity for enhanced wound healing

Baicalin, extracted from traditional Chinese medicine Scutellaria baicalensis Georg, possesses multiple pharmacological activities and has great potential for chronic skin wound repair. However, the poor solubility and lack of suitable vehicles greatly limit its further application. Herein, we proposed a convenient and robust strategy, employing PBS solution as solvent, to enhance the solubility of baicalin. Furthermore, we constructed injectable baicalin/F127 hydrogels to study their application in skin wound treatment. The composition and temperature sensitivity of baicalin/Pluronic® F-127 hydrogels were confirmed by FTIR and rheological testing, respectively. In vitro release measurement indicated that the first order model was best fitted with the release profile of baicalin from hydrogel matrix. Besides, MTT assay, AO/EO staining assay as well as hemolytic activity test revealed the excellent cytocompatibility of baicalin/F127 hydrogels. Antioxidant activity assay demonstrated the cytoprotective activity of baicalin/F127 hydrogels against reactive oxygen species (ROS). Furthermore, the in vivo experiments exhibited the ability of baicalin/F127 hydrogel to accelerate wound healing. In conclusion, this novel injectable baicalin/F127 hydrogel should have bright application for chronic wound treatment.     

Self-Healable Polyelectrolytes with Mechanical Enhancement for Flexible and Durable Supercapacitors

The practical application of advanced personalized electronics is inseparable from flexible, durable, and even self-healable energy storage devices. However, the mechanical and self-healing performance of supercapacitors is still limited at present. Herein, highly transparent, stretchable, and self-healable poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPSA)/poly(vinyl alcohol) (PVA)/LiCl polyelectrolytes were facilely prepared by one-step radical polymerization. The cooperation of PAMPSA and PVA significantly increased the mechanical and self-healing capacity of the polyelectrolyte, which exhibited superior stretchability of 938 %, stress of 112.68 kPa, good electrical performance (ionic conductivity up to 20.6 mS cm⁻¹), and high healing efficiency of 92.68 % after 24 h. After assembly with polypyrrole-coated single-walled carbon nanotubes, the resulting as-prepared supercapacitor had excellent electrochemical properties with high areal capacitance of 297 mF cm⁻² at 0.5 mA cm⁻² and good rate capability (218 mF cm⁻² at 5 mA cm⁻²). Besides, after cutting in two the supercapacitor recovered 99.2 % of its original specific capacitance after healing for 24 h at room temperature. The results also showed negligible change in the interior contact resistance of the supercapacitor after ten cutting/healing cycles. The present work provides a possible solution for the development of smart and durable energy storage devices with low cost for next-generation intelligent electronics.     

Photo-RAFT Polymerization for Hydrogel Synthesis through Barriers and Development of Light-Regulated Healable Hydrogels under NIR Irradiation

We report an aqueous and near-infrared (NIR) light mediated photoinduced reversible addition–fragmentation chain transfer (photo-RAFT) polymerization system catalyzed by tetrasulfonated zinc phthalocyanine (ZnPcS₄⁻) in the presence of peroxides. Taking advantage of its fast polymerization rates and high oxygen tolerance, this system is successfully applied for the preparation of hydrogels. Exploiting the enhanced penetration of NIR light, photoinduced gelation is effectively performed through non-transparent biological barriers. Notably, the RAFT agents embedded in these hydrogel networks can be reactivated on-demand, enabling the hydrogel healing under NIR light irradiation. In contrast to the minimal healing capability (<15 %) of hydrogels prepared by free radical polymerization (FRP), RAFT-mediated networks display more than 80 % recovery of tensile strength. Although healable polymer networks under UV and blue lights have already been established, this work is the first photochemistry system using NIR light, facilitating photoinduced healing of hydrogels through thick non-transparent barriers.