pH-Responsive Multinetwork Hydrogel with Antibacterial, Anti-Inflammatory, and Microenvironment-Modulating Properties for Enhanced Hemostasis and Wound Healing.
A multifunctional hydrogel with antibacterial, antioxidant, and anti-inflammatory properties for accelerated wound healing is presented.
Abstract
Hydrogel dressings have emerged as versatile platforms for wound management. However, effective treatment remains challenging due to complex wound environments involving hemorrhage, bacterial infection, and inflammation. Herei, a multifunctional pH-responsive hydrogel (PCOB 1) was developed via multinetwork cross-linking and freeze-thaw cycles using oxidized pullulan (OP), collagen, poly(vinyl alcohol) (PVA), and borax, and was impregnated with in situ stabilized silver nanoparticles (AgNPs). The incorporation of AgNPs endowed the hydrogel with pH-triggered antibacterial activity, achieving >99% killing of E. coli and S. aureus, efficient biofilm disruption, >90% ROS/RNS scavenging, and catalase-mimetic activity. The hydrogel demonstrated rapid gelation, self-healing, and hemostasis within 33.3 s. The hydrogel promoted macrophage polarization from M1 to M2, enhanced collagen deposition, re-epithelialization, and granulation tissue formation, achieving 98.5 ± 0.6% wound closure by day 14 in vivo. This study presents a multifunctional hydrogel with antibacterial, antioxidant, and anti-inflammatory properties for accelerated wound healing.
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
A precision-engineered hydrogel that integrates structural integrity with environment-triggered delivery and seamlessly coupling nanocontrolled release with microenvironmental sensing is presented, presenting a precision-engineered platform for the synergistic treatment of recalcitrant diabetic wounds.
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
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
Conventional wound dressings often fail to integrate rapid hemostasis, antibacterial protection, and a pro-regenerative microenvironment, leading to persistent infection and delayed healing in complex wounds. Herein, we report a multifunctional self-adhesive hydrogel for integrated hemostatic, antibacterial, and regenerative wound management with a synergistic dual-crosslinked network. The hydrogel is composed of methylacrylamide-modified type I collagen (ColMA), o-nitrobenzene-modified hyaluronic acid (HANB), and methylacrylamide-modified chitosan (CSMA), and can rapidly form in situ under UV irradiation through free-radical polymerization of methacrylamide groups and Schiff base reactions between HANB and amino groups on ColMA/CSMA. Once applied to infected wounds, the hydrogel rapidly seals the wound bed and adheres tightly to the tissue, where HANB contributes hemostatic and adhesive properties, CSMA provides intrinsic antibacterial activity to inhibit bacterial colonization, and ColMA offers extracellular matrix-mimicking cues to support cell adhesion and tissue regeneration. Through this coordinated mechanism, the hydrogel not only controls bleeding and reduces infection risk at the early stage but also promotes the growth of granulation tissue, re-epithelialization, and matrix reconstruction during the subsequent repair phase. This platform integrates wound closure, antibacterial defense, and tissue regeneration into a single dressing system, acting as a promising strategy for the treatment of infected wounds.
She-Ji Weng, Zhongqin Lin, Kai Tan et al.· ACS Biomaterials Science & E...· 0 citations
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.