It is demonstrated 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.
Abstract
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.
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.
Insha Kakroo, Nayeema Gull, Insha Mehraj et al.· ACS Applied Bio Materials· 0 citations
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
An integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation revealed that the therapeutic efficacy of sustained local α-MG delivery involves the modulation of the PPAR-γ pathway.
Yuan Ma, Xu Liu, Zhewen Deng et al.· International Journal of Bio...· 0 citations
Hydrogels derived from natural polymers are gaining attention in wound dressings due to their extracellular matrix–mimicking structures and tunable properties. In this study, carboxymethyl cellulose (CMC) based hydrogels were developed via graft copolymerization of acrylic acid (AA) and diallyldimethylammonium chloride (DADMAC), with varying DADMAC content, to obtain multifunctional wound healing materials. The hydrogels were characterized to evaluate their structural, thermal, and morphological properties. Results showed successful grafting, increased porosity (up to ~ 45%) with higher DADMAC content, enhanced thermal stability and pH-responsive swelling behavior. Controlled biodegradation was observed over 21 days, with weight loss ranging from 17.5 to 25%. In vitro cytocompatibility evaluated by assay on human fibroblast (BJ−1) cells showed high cell viability (> 86%), while scratch wound assays demonstrated improved cell migration and proliferation
.
Antibacterial activity assessed using the colony-forming unit method against
Staphylococcus aureus
and
Escherichia coli
revealed effective bacterial growth reduction for DADMAC-containing hydrogels.These results indicate that the developed CMC-based hydrogels possess suitable physicochemical, biological, and antimicrobial properties for potential wound dressing applications.
Hebatalla E. Kandil, A. Soliman, E. A. Ali· Cellulose· 0 citations
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
Chronic infected wounds are often characterized by persistent bacterial colonization, biofilm formation, excessive oxidative stress, and prolonged inflammation, which severely impair tissue regeneration. To address these challenges, a multifunctional wound dressing capable of antibacterial activity and microenvironment modulation was developed. In this study, amide-modified hyaluronic acid (HA-ADH) was used as the matrix, and a dynamic coordination network was constructed via Cu2+-hydrazide interactions to form an in situ HA-Cu hydrogel. Curcumin-loaded DSPE-PEG2000 micelles were further incorporated to obtain a pH-responsive composite hydrogel (HA-Cu/Cur). The prepared hydrogel exhibited a porous interconnected structure, along with favorable injectability, self-healing capability, tissue adhesiveness, moderate swelling, controllable degradability, and pH-responsive behavior under acidic conditions. In vitro antibacterial assays demonstrated that both HA-Cu and HA-Cu/Cur effectively inhibited the growth and biofilm formation of Escherichia coli and Staphylococcus aureus. The antibacterial activity was associated with disruption of bacterial morphology, depletion of intracellular ATP, and induction of reactive oxygen species, while HA-Cu/Cur showed enhanced performance in antibiofilm activity and oxidative stress-related effects compared with HA-Cu. Cytocompatibility studies revealed that the hydrogel extracts exhibited negligible cytotoxicity toward L929 fibroblasts and RAW 264.7 macrophages, while promoting fibroblast migration and significantly reducing the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in lipopolysaccharide-stimulated RAW 264.7 cells, with HA-Cu/Cur showing a more pronounced anti-inflammatory effect. In summary, the HA-Cu/Cur hydrogel integrates the antibacterial and pro-healing properties of Cu2+ with the antioxidant and anti-inflammatory activities of curcumin. The hydrogel effectively inhibited the growth and biofilm formation of both E. coli and S. aureus, reduced the expression of TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages, and promoted fibroblast migration, demonstrating its potential as a multifunctional wound dressing for the management of infected wounds.
Jiajie Chen, Haotian Huang, Yihan Wang et al.· Molecules· 1 citation