The HA-Cu/Cur hydrogel integrates the antibacterial and pro-healing properties of Cu2+ with the antioxidant and anti-inflammatory activities of curcumin, demonstrating its potential as a multifunctional wound dressing for the management of infected wounds.
Abstract
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.
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.
A multifunctional peptide-based antibacterial hydrogel (PAHG) for treating infected wounds, constructed through the incorporation of Cys-Arg-NH2 (CR)-Ag nanoassemblies into a bioactive matrix with excellent antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus.
Heng Ge, Wen Yuan, Yulin Sun et al.· Journal of materials chemist...· 0 citations
Gel-P@Z exhibited a slow and sustained release of Gly-POX and achieved >99% antibacterial efficacy against drug-resistant bacteria without toxicity, and RNA-seq analysis revealed that Gel-P@Z accelerated healing via upregulation of the TGF-β signaling pathway, driving fibroblast-to-myofibroblast transition and promoting tissue fibrosis.
Chuanliang Fu, Wenjing Zhang, Renyuan Wang et al.· Materials Today Bio· 0 citations
Chronic diabetic wounds are characterized by persistent oxidative stress, impaired angiogenesis, and biofilm-associated infections, necessitating multifunctional biomaterials capable of modulating the wound microenvironment. Herein, we report an amyloid-reinforced hyaluronic acid (HA) composite hydrogel that integrates mechanical robustness, controlled drug delivery, and bioactive functionality within a single platform. The hydrogel is constructed through interpenetrating protein-polysaccharide networks, where thermally induced bovine serum albumin amyloid fibrils act as reinforcing scaffolds within the HA matrix via hydrogen bonding and chain entanglement. This architecture enhances viscoelastic properties, swelling behavior, and structural stability compared to nonreinforced systems. Curcumin is incorporated as a multifunctional therapeutic agent, exhibiting sustained and pH-responsive release governed by hydrophobic and π-π interactions within the composite network. The hydrogel demonstrates pronounced antibacterial and antibiofilm activity against both Gram-positive and Gram-negative bacteria, which is further amplified under near-infrared (NIR) irradiation via photothermal effects. In vitro studies confirm excellent cytocompatibility, hemocompatibility, and enhanced fibroblast migration, indicating favorable cellular interactions. Importantly, in a streptozotocin-induced diabetic wound model, the composite hydrogel significantly accelerates wound closure, promotes collagen deposition and neovascularization, and restores oxidative stress biomarkers toward physiological levels. Mechanistically, the combined integration of amyloid-mediated mechanical reinforcement, HA-driven bioactivity, and curcumin-enabled therapeutic functionality enables the simultaneous regulation of infection, inflammation, and tissue regeneration. This study establishes a protein-polysaccharide hybrid hydrogel platform that couples structural reinforcement with stimuli-responsive therapeutic delivery, offering a promising strategy for advanced diabetic wound management and translational biomaterial design.
Saurabh Kumar Srivastava, Priyanka Singh, Shikha Tripathi et al.· ACS Applied Materials and In...· 0 citations
Abstract Bacterial infection remains a major barrier to effective wound healing by disrupting immune homeostasis, sustaining chronic inflammation and impairing tissue regeneration. Herein, we present a green, sustainable strategy for fabricating antibacterial, immunomodulatory bioactive granular hydrogels (GHs) for infected wound regeneration. An amino-alcohol ether prepolymer (MP) was first synthesized via epoxy–amine click chemistry and subsequently complexed with the natural polyphenol tannic acid (TA), thereby triggering phase-separation-driven supramolecular self-assembly into GHs without additional crosslinkers. To elucidate the polymer assembly mechanism and identify the bioactive concentration threshold, agarose was introduced as a fourth component to construct A/MP@TA GHs. The results showed that increasing the agarose content progressively transformed the granular architecture into a sheet-like network, whereas A/MP@TA3, which represents the lowest agarose ratio that preserves the granular morphology, exhibited potent antibacterial and antioxidant activities and enhanced fibroblast migration. In a bacteria-infected wound, A/MP@TA3 still markedly accelerated wound closure while promoting collagen deposition and angiogenesis. Mechanistically, sustained TA release reprogrammed the microenvironment by activating the KEAP1/Nrf2/HO-1 and suppressing NF-κB signaling, thereby driving macrophage polarization toward a pro-regenerative M2 phenotype. This work establishes a simple, cost-effective and environmentally friendly platform for fabricating multifunctional hydrogel dressings and provides a biomaterial-based strategy for remodeling the immune microenvironment.
