Multifunctional hydrogel dressings remain highly sought after for the promotion of skin wound regeneration. In the present study, multifunctional CHS-DA/HACC (CH) hydrogels with an interpenetrated network were constructed using hydroxypropyl trimethyl ammonium chloride modified chitosan (HACC) and dopamine-modified chondroitin sulfate (CHS-DA), using genipin as crosslinker. The synthesis of HACC and CHS-DA was effectively confirmed using Fourier transform infrared (FT-IR) analysis and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy. The prepared CH hydrogels exhibited a network of interconnected pores within the microstructure. Furthermore, rheological testing demonstrated that CH hydrogels exhibited strong mechanical properties, stability, and injectability. Further characterization investigations showed that the CH hydrogels showed favorable self-healing and self-adhesion properties. It was also shown that increasing HACC concentration ratio was positively correlated with the antibacterial activity of CH hydrogels, as evidenced by their resistance to Escherichia coli and Staphylococcus aureus. Additionally, Cell Counting Kit-8 (CCK-8) tests, fluorescent images, and a cell scratch assay demonstrated that CH hydrogels had good biocompatibility and cell migration ability. The multifunctional interpenetrated network hydrogels were shown to have good antibacterial properties, antioxidant properties, stable storage modulus and loss modulus, injectable properties, self-healing properties, and biocompatibility, highlighting their potential as wound dressings in wound healing applications.

Multifunctional hydrogels with an interpenetrated network structure have shown great potential for biomedical and tissue-regeneration applications. In this work, the biomedical hydrogel was fabricated with an interpenetrated network based on dopamine grafted gelatin (DA-Gel), and genipin crosslinked quaternary ammonium chitosan (QCS), incorporating epigallocatechin gallate (EGCG). The EDC/NHS and Schiff-base bond connections occurred in the hydrogels, as confirmed by Fourier-transform infrared (FT-IR) analysis. The properties of the fabricated hydrogels, including microstructure, degradation rate, adhesive strength, mechanical strength, and rheological behavior, can be regulated by adjusting the DA-Gel/QCS ratio or by using different crosslinking approaches. In addition, the fabricated hydrogels exhibited self-healing properties and strong adhesion to various materials and organs. Furthermore, the hydrogels performed good antibacterial activity against the typical bacteria, Escherichia coli and Staphylococcus aureus. EGCG encapsulated hydrogels displayed excellent antioxidant activities and good hemocompatibility. The hydrogels also demonstrated excellent cytocompatibility and good cell migration ability. The above results provide a facile approach to fabricate the biomedical hydrogels with a regulated network structure and multifunctional characteristics with potential in biomedical applications.

Background/Objectives: Tissue bio-adhesives have gained significant attention as efficient alternatives to conventional wound closures, which are often hindered by insufficient adhesion and poor biocompatibility. Methods: Inspired by nature’s robust wet-adhesion strategies that use dynamic covalent interactions, we have reported a facilely fabricated hydrogel bio-adhesive based on lactobionic acid-conjugated polyethylenimine (LA-PEI) and oxidized dextran (ODex) via Schiff base linkages. Results: The prepared hydrogels exhibited three-dimensional interconnected porous networks, regulated swelling ratios, typical viscoelasticity, shear-thinning behavior, and self-healing ability. Notably, the swelling ratios of the hydrogels depended on composition, and OLP11 displayed the highest swelling ratio of over 1500%. The hydrogel bio-adhesives exhibited strong adhesion to various surfaces, including glass, metal, plastic, rubber, and wood, as well as to different chicken organs, including the heart, liver, spleen, and stomach. Furthermore, the hydrogels exhibited excellent ABTS radical-scavenging activity, effective intracellular reactive oxygen species (ROS) scavenging, and good hemocompatibility, with hemolysis ratios of all hydrogels close to 0%, below the threshold of 5%. After culturing with NIH 3T3 fibroblasts, the hydrogels demonstrated good cytocompatibility and promoted cell proliferation, with cell viabilities on day 3 reaching over 90%. Conclusions: This design yields multifunctional hydrogel bio-adhesives, showing strong promise for wound care and tissue repair applications.

The drug-encapsulated hybrid hydrogels possessed several expected properties, including porous microstructure, conductivity, adhesive strength, antioxidant activity, antibacterial properties, and cytocompatibility, and have great potential in biomedical applications, such as skin wound hydrogel dressings and bio-adhesives. In this paper, the quercetin-loaded hybrid hydrogels (SSA-QRs) were fabricated using silk fibroin (SF), alginate, and silver-doped reduced graphene oxide (Ag@rGO) nanosheets, incorporating quercetin-encapsulated PF-127 (PF127-QR) micelles. Scanning electron microscopy (SEM) images confirmed that the fabricated hybrid hydrogels possessed an interconnected porous microstructure. The mechanical properties of hydrogels could be regulated by adjusting the content of incorporated Ag@rGO nanosheets and PF127-QR micelles. Furthermore, the obtained SSA-QR hydrogels displayed the expected swelling properties, and the swelling rates could reach 1200–1700% in 120 min, in the equilibrium state. The fabricated SSA-QR hydrogels possessed apparent conductivity and self-healing ability. In addition, SSA-QR hydrogels exhibited strong adhesive performance on the surface of different materials, including skin, metal, wood, plastic, and glass. The typical antibacterial testing using Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) confirmed the excellent antibacterial activities of SSA-QR hydrogels. Moreover, SSA-QR hydrogels displayed good antioxidant ability and intracellular ROS scavenging ability. However, the increased content of Ag@rGO nanosheets could cause a great increase in the hemolysis ratio for SSA-QR hydrogels. Fluorescent images, cell counting kit-8 (CCK-8) assay, and cell scratch testing confirmed their excellent cytocompatibility and cell pro-migration ability. The available results demonstrated a facile strategy to prepare the quercetin-loaded hydrogel for applications of wound hydrogel dressing and bio-adhesives.

Excessive reactive oxygen species (ROS) and bacterial infection were the important obstacles to impaired wound healing. Herein, by the use of innate bioactivities of natural polysaccharides and flavonoid glycosides, a multifunctional hydrogel was engineered through the Schiff base reaction between oxidized fucoidan (oFu) and lysine-modified chitosan (CS-Ly) for wound dressing. Rutin and silver nanoparticle (AgNP)-modified polydopamine (PDA) nanoparticles were incorporated into the hydrogel matrix, thereby exhibiting favorable ROS scavenging ability and adhesive property. Moreover, the hydrogel demonstrated strong antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with antibacterial rates of 81.8% and 78.2%, respectively. Moreover, the dynamic crosslinking endowed the hydrogel with adjustable degradation behavior and self-healing ability. When cocultured with NIH-3T3 cells, the hydrogel exhibited good biocompatibility. Based on the above results, these multifunctional hydrogels with excellent performance have great appealing potential in clinical materials for wound healing.

Hydrogel bio-adhesives have gained great attention in wound healing and tissue regeneration applications because conventional wound closures are often hindered by insufficient adhesion and poor biocompatibility. Considering that dynamic covalent interactions facilitate robust wet adhesion in hydrogels, we fabricated a Schiff base hydrogel bio-adhesive based on oxidized chondroitin sulfate (OCS) and polyethylenimine (PEI), and employed different degrees of OCS oxidation to regulate the physicochemical properties of the bio-adhesives. In this system, aldehyde groups of OCS react with amino groups of PEI to form covalent imine crosslinks, while physical hydrogen bonds also contribute as supplementary interactions. The fabricated hydrogel bio-adhesives demonstrated a three-dimensional interconnected microstructure and regulated equilibrium swelling ratios. The rheological tests also confirmed the typical viscoelasticity of the hydrogels and their shear-thinning behavior. The obtained hydrogel bio-adhesives demonstrated rapid and autonomous self-healing ability and strong adhesion to the surfaces of various matrices and wet organs, including wood, glass, metal, plastic, rubber, and heart, liver, spleen, stomach, and lung tissue. Furthermore, an ABTS radical scavenging assay confirmed their potent antioxidant activity. The hydrogels possessed effective antibacterial activities against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The hydrogels exhibited good hemocompatibility, effective intracellular reactive oxygen species (ROS) scavenging activity, favorable cytocompatibility, and promoted cell proliferation. These results confirmed the fabricated hydrogels via Schiff base connections for biomedical applications and provided a facile design for biomedical hydrogel bio-adhesives.