Rapid hemostasis, oxidative stress resistance, and minimally invasive administration are crucial performance requirements for high-performance wound covering. Inspired by the dynamic remodeling properties of the native extracellular matrix, we fabricated a multifunctional injectable hydrogel through dynamic Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS), combined with magnesium ion (Mg²⁺) coordination. The effects of Mg²⁺ content on hydrogel properties were systematically investigated. The hydrogels gelled rapidly under physiological conditions and showed good injectability, self-healing behavior, and favorable adhesion to moist tissues. Notably, Mg²⁺ incorporation significantly enhanced hemostatic performance in a mouse tail amputation model, reducing blood loss from 391.7 mg to approximately 75 mg and shortening hemostasis time from 151.7 s to 50.3 s. The 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging efficiency reached approximately 80%, and the hydrogel effectively scavenged intracellular reactive oxygen species (ROS) without compromising cytocompatibility or fibroblast activity. This study presents a biomimetic and easily prepared hydrogel platform that integrates pro-coagulant activity, redox regulation, and on-demand injectability, showing translational potential as bioactive wound covering for bleeding control and oxidative microenvironment regulation.

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.

Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds.

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.