Jul 2026· ACS Applied Bio Materials· 0 citations· 47 references
Medicine
TL;DR
A multifunctional hydrogel patch developed by chemically modifying chitosan with N-acetylsulfonyl chloride and forming a cross-linked network with polyvinylpyrrolidone (PVP) represents a promising multifunctional dressing for the effective management of infected wounds.
Abstract
Chronic infected wounds remain a significant clinical challenge due to persistent microbial colonization, excessive reactive oxygen species (ROS) generation, and impaired tissue regeneration. These pathological conditions disrupt key healing processes, such as re-epithelialization, angiogenesis, and extracellular matrix (ECM) remodeling, necessitating advanced wound dressings capable of simultaneously addressing infection and oxidative stress. In this work, a multifunctional hydrogel patch was developed by chemically modifying chitosan with N-acetylsulfonyl chloride (CS-NASC) and forming a cross-linked network with polyvinylpyrrolidone (PVP), followed by the incorporation of silver nanoparticles (AgNPs) and resveratrol (RSV). FTIR spectroscopy confirmed successful chemical modification and intermolecular interactions within the hydrogel matrix. The hydrogel exhibited pH-responsive swelling behavior, achieving a high swelling ratio of approximately 1500% at pH 7.4, indicating excellent fluid absorption capacity under wound-relevant conditions. Scanning electron microscopy revealed a porous architecture with an average pore size of ∼151 μm, favorable for exudate absorption and nutrient transport. The developed hydrogel demonstrated strong antibacterial activity, with zones of inhibition of 18.0 ± 0.1 mm against Staphylococcus aureus and 20.0 ± 0.1 mm against Escherichia coli, attributed to the synergistic antimicrobial effects of NASC and AgNPs. Additionally, the presence of RSV imparted significant antioxidant activity, with 65-85% DPPH radical scavenging efficiency. Cytocompatibility evaluation using the MTT assay confirmed excellent cell viability (>95% viability), while rheological analysis indicated stable viscoelastic behavior with G' > G″, ensuring structural integrity suitable for wound application. In vivo evaluation using a coinfected wound model demonstrated that the hydrogel patch significantly enhanced wound healing, achieving 91.96% wound contraction within 14 days, along with a marked reduction in bacterial load and increased collagen deposition (0.6643 μg/mg hydroxyproline) compared to control groups. Histopathological analysis further confirmed improved tissue regeneration, including enhanced re-epithelialization and collagen organization. Overall, the CS-NASC/AgNPs/RSV/PVP hydrogel patch represents a promising multifunctional dressing for the effective management of infected wounds.
Impaired healing of chronic wounds typically stems from persistent oxidative stress, bacterial infection, and cellular dysfunction. Designing a multifunctional hydrogel dressing capable of adhesion, antioxidant activity, antibacterial ability, and cytocompatibility has demonstrated potential in wound healing applications. In this study, HTP composite hydrogels were fabricated based on thiolated chitosan (TCS) and methacrylated hyaluronic acid (HAMA) by incorporating polyethylene glycol diacrylate (PEGDA) and gelatin via the synergistic crosslinking of thiol-Michael addition and free-radical photopolymerization. Comprehensive characterization revealed that the hydrogel possessed an interconnected porous microstructure, appropriate swelling properties, and controllable degradation profiles, accompanied by pronounced shear-thinning behavior and tissue-adhesive capabilities. The obtained hydrogels demonstrated significant antibacterial activity against Staphylococcus aureus and Escherichia coli. Furthermore, the HTP hydrogels exhibited remarkable antioxidant capacity, scavenging DPPH and ABTS radicals. Additionally, the intracellular reactive oxygen species (ROS) scavenging ability was validated using NIH-3 T3 cells. Hemolysis assays and cytocompatibility evaluations confirmed the favorable hemocompatibility of the HTP hydrogels, which significantly promoted fibroblast proliferation and migration, indicating their substantial potential for wound healing applications.
Lei Nie, Xinran Li, Mengfei Feng et al.· International Journal of Bio...· 0 citations
Wound management, especially for infected and diabetic ulcers, poses a persistent clinical challenge, largely attributed to sustained inflammation, bacterial colonization, and compromised tissue regeneration. Herein, a multifunctional hydrogel (CBOS) with integrated therapeutic properties was developed through Schiff base reaction between betaine-modified chitosan (CSBT) and oxidized sodium alginate (OSA), with poly(vinyl alcohol) and sodium borate incorporated to enhance network stability. The resulting CBOS hydrogel exhibited a uniform porous microstructure, robust viscoelasticity, high swelling capacity, and appropriate water vapor transmission. Comprehensive biocompatibility assessments confirmed its negligible cytotoxicity and applicable hemocompatibility. The hydrogel demonstrated broad-spectrum tissue adhesion and potent hemostatic efficacy in murine tail incision and liver hemorrhage models. Moreover, CBOS displayed antioxidant activity by scavenging multiple free radicals and reducing intracellular reactive oxygen species in H2O2-stressed fibroblasts. Antibacterial evaluations revealed potent activity against S. aureus, with molecular docking studies suggesting multitarget interactions with key bacterial proteins, including AgrA, ClpP, and FtsZ. In vitro, CBOS significantly enhances fibroblast migration. In vivo, the hydrogel accelerated healing in both S. aureus-infected full-thickness wounds and diabetic chronic wounds, as evidenced by reduced bacterial burden, attenuated inflammatory responses, enhanced collagen deposition, and promoted neovascularization. With its integrated hemostatic, antioxidant, antibacterial, and pro-regenerative properties, the CBOS hydrogel offers a viable and attractive therapeutic approach for complex wound tissue repair.
Xueyan Hou, Yanan Lu, Tenglong Xu et al.· ACS Applied Materials and In...· 0 citations
Diabetic skin injury is a serious clinical challenge due to impaired healing and infection. Here, we developed a sandcastle worm-inspired hydrogel featuring a phosphate-catechol-amine synergistic network based on a poly(acrylic acid-co-acrylamide) network, functionalized with dopamine-grafted cellulose nanofibers (DA-PCNF) and quaternized chitosan (QCS), to accelerate diabetic wound healing. The hydrogel exhibits strong tissue adhesion (78.82 ± 2.55 kPa) and broad-spectrum antibacterial activity (99.67% killing of Escherichia coli and 99.55% killing of Staphylococcus aureus in vitro). More importantly, it exhibits pH-responsive swelling and adhesion behaviors, maintaining robust adhesion under mildly acidic wound conditions while attenuating adhesion under neutral conditions to facilitate atraumatic dressing removal. Antioxidant assays indicated that the hydrogel exhibits scavenging activity against various free radicals with efficiencies ranging from 30% to 40%, attributable to the catechol groups. In vivo application of the hydrogel to infected diabetic wounds significantly accelerated healing (99.82%, on day 12 after Pseudomonas aeruginosa-infected wound formation), with reduced inflammation and enhanced tissue regeneration. These findings demonstrate that the catechol-nanocellulose/chitosan polymeric hydrogel effectively overcomes adhesion, infection, and oxidative stress barriers in diabetic wound healing, making it a promising candidate for difficult-to-heal chronic ulcers.
Excessive oxidative stress, persistent chronic inflammation, impaired angiogenesis, and delayed extracellular matrix (ECM) remodeling contribute to the chronic non-healing of diabetic wounds, which is a major clinical challenge worldwide that decreases patients' quality of life. Herein, a novel photocrosslinked hydrogel based on gallic acid functionalized chitosan methacryloyl (GA-CSMA) and fish gelatin methacryloyl (FGelMA) was developed for diabetic chronic wound treatment without exogenous therapeutic agents to provide structural stability and intrinsic bioactivity. Quantitative pore-size analysis and bulk mechanical testing confirmed that incorporation of GA-CSMA generated a denser porous architecture and improved the compressive and tensile mechanical performance of the FGelMA-based hydrogel. In addition, the optimized hydrogel formulation showed cytoprotective effects against oxidative stress by reducing intracellular reactive oxygen species (ROS) and exhibited macrophage-associated immunomodulatory activity, as evidenced by reduced pro-inflammatory mediators and enhanced pro-healing marker expression. Furthermore, GM/G-CMIII significantly promotes the proliferation, migration and in vitro angiogenesis. In vivo experiments further reveal that the hydrogel significantly accelerated wound closure via improved re-epithelialization, collagen production, and neovascularization and modulated macrophage polarization toward M2 phenotype in full-thickness wound model in streptozotocin (STZ)-induced diabetic mice. Therefore, this photocrosslinked hydrogel system can serve as a promising wound dressing for hard-to-heal chronic wounds.
D. Park, Se-Chang Kim, Geum-Jae Jeong et al.· International Journal of Bio...· 0 citations
Chronic wounds pose a major clinical challenge due to a complex pathophysiological condition. It is characterized by persistent inflammation, excessive oxidative stress, and a high risk of bacterial infection, which hinders tissue repair. To address this, a multifunctional hydrogel dressing based on gallic acid conjugated chitosan (G‐CHI) and integrated with simvastatin and heparin‐functionalized Ag/Zn‐doped bioactive glass (HBG). The incorporation of gallic acid improved the structural integrity and viscoelastic behavior of the hydrogel. The release kinetics study demonstrated controlled liberation of Ag
+
and Zn
2+
ions within biologically safe limits over 24 h, while simvastatin exhibited diffusion‐controlled release behavior. The hydrogel also exhibited desirable adhesive properties, indicating its suitability as a wound dressing material. In vitro biofunctional assays showed enhanced antioxidant activity (~75% free radical scavenging), hemocompatibility (< 5% hemolysis), and effectiveness against both
Staphylococcus aureus
and
Escherichia coli
(> 90% efficacy in time kill assay). Further, synergistic release of simvastatin and bioglass showed enhanced proliferation of fibroblast (NIH 3T3), keratinocyte (HaCaT), and endothelial cells (SVEC), accompanied by increased collagen deposition compared to control groups. These findings suggest that the synthesized hydrogel (BSG‐CHI) provides a favorable microenvironment for tissue regeneration and wound management applications.
Durgesh Kumar, Suhela Tyeb, Baby Shruit Shukla et al.· MedComm – Biomaterials and A...· 0 citations
The healing of chronic wounds remains a complex and challenging clinical issue. Antioxidant and antibacterial treatments play a crucial role in facilitating the wound healing process. Multifunctional hydrogels derived from natural products have shown promising potential in promoting skin tissue regeneration. In this study, a composite multifunctional hydrogel (CS/CSGA-DAHA) was developed by incorporating dopamine-modified hyaluronic acid (DAHA) and gallic acid-modified chitosan (CSGA), crosslinked through a combination of poly-electrolyte interactions and Schiff base reactions. The resulting hydrogel exhibited a porous microstructure, elastic solid-like mechanical behavior, and effective antibacterial activity against both Gram-negative and Gram-positive bacteria. Furthermore, the cytocompatibility of the hydrogel was confirmed through CCK-8 assay and fluorescent imaging analysis after co-cultivation with L929 fibroblast cells. This research introduces an innovative multifunctional hydrogel with promising potential as a wound dressing for various applications in chronic wound management.