Jul 2026· International Journal of Biological Macromolecules· Vol 374, pp.
153312
· 0 citations· 62 references
Medicine
TL;DR
In vitro and in vivo evaluations confirmed that the hydrogel was highly biocompatible and provided anti-infective, anti-oxidative, and anti-inflammatory effects during the early stages of healing, followed by an increase in angiogenesis and acceleration of the wound healing process.
Abstract
Bacteria-infected wounds are very difficult to treat, largely because the pathological microenvironment involved is dynamic. The requirements for infected wound repair are multifaceted, and conventional hydrogel dressings cannot adequately meet them due to their limited functionality. In this study, we report the construction of a multifunctional, pH/ROS dual-responsive hydrogel based on dynamic Schiff base and borate ester linkages. Oxidized pullulan (OPu) was used to fabricate the hydrogel, and the bioactive polyphenol chlorogenic acid (CA) acted as the crosslinking agent. Next, we synthesized the carbon dots derived from Isatis root (IR-CDs) using the hydrothermal method and subsequently incorporated them into the hydrogel. The hydrogel exhibited excellent injectability and self-healing capability, enabling application at irregular wound sites. Under the acidic and oxidative conditions of infected wounds, the hydrogel gradually dissociated, releasing IR-CDs and CA in a controlled manner. IR-CDs exhibited potent antibacterial activity, while CA and IR-CDs in combination efficiently scavenged excessive reactive oxygen and nitrogen species, therefore promoting tissue regeneration and reducing inflammation. Both in vitro and in vivo evaluations confirmed that the hydrogel was highly biocompatible and provided anti-infective, anti-oxidative, and anti-inflammatory effects during the early stages of healing, followed by an increase in angiogenesis and acceleration of the wound healing process. The hydrogel developed in this study is versatile and can serve as a promising and effective biomaterial platform for managing bacteria-infected wounds.
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.
Muhammad Shahid, Mujahid Niaz, Huma Ghazal et al.· Biomacromolecules· 0 citations
Diabetic foot ulcers (DFUs) remain a major clinical challenge, driven by the convergent effects of microbial infection, chronic inflammation, oxidative stress, and inadequate neovascularization that collectively disrupt tissue repair. Although the integrin αvβ3 agonist peptide FZ1 exhibits promising pro-healing activity, limited delivery control and insufficient functional versatility have restricted its clinical translation. To overcome these constraints, a pH-responsive hyaluronic acid (HA)-based hydrogel, HA-c-FZ1, was developed to enable intelligent acidity-triggered peptide release while integrating antimicrobial activity, reactive oxygen species (ROS) scavenging, and inflammation control within a single wound dressing platform for diabetic wound repair.
First, photo-crosslinkable oxidized methacrylated HA (O-HAMA) was synthesized and covalently linked to FZ1 through a pH-labile Schiff base bond, yielding HA-c-FZ1 hydrogels at three concentrations (2%, 3%, and 4%). Hydrogel morphology, swelling behavior, mechanical properties, peptide-loading efficiency, pH-responsive release, antioxidant activity, antibacterial activity, biocompatibility, and anti-inflammatory effects were systematically evaluated in vitro. Therapeutic efficacy was then assessed in a diabetic mouse model with infected full-thickness skin wounds through wound closure analysis, histological staining, immunofluorescence detection of macrophage polarization markers (iNOS and ARG) and angiogenic markers (α-SMA and VEGF), and laser speckle imaging of blood perfusion. Transcriptomic profiling, RT-qPCR, and western blotting were performed to define the molecular mechanisms underlying HA-c-FZ1-mediated wound repair.
HA-c-FZ1 formed a homogeneous porous hydrogel network with predictable swelling behavior, tunable mechanical performance, high FZ1 loading efficiency, and accelerated peptide release under acidic conditions. In vitro, HA-c-FZ1 promoted keratinocyte proliferation and migration, reduced ROS accumulation, and inhibited Staphylococcus aureus and Escherichia coli survival. In infected diabetic wounds, HA-c-FZ1 suppressed bacterial burden and accelerated wound closure, accompanied by enhanced re-epithelialization, collagen deposition, angiogenesis, and local blood perfusion. Mechanistic analyses indicated that HA-c-FZ1 attenuated NF-κB-associated inflammatory signaling, promoted M2 macrophage polarization, and activated FAK-AKT-dependent angiogenic responses.
HA-c-FZ1 functions as a pH-responsive hydrogel dressing that combines peptide delivery and antimicrobial, redox-regulatory, immunomodulatory, and pro-angiogenic functions. These findings position it as a therapy for chronic diabetic wound repair by simultaneously addressing infection, inflammation, oxidative stress, and vascular regeneration.
Zhe Fu, Jingyu Jiang, Yutong Wu et al.· Burns & Trauma· 0 citations
Infected diabetic wounds are complicated by bacterial infection, oxidative stress, and hyperglycemia, limiting conventional monotherapies. Combination therapies suffer from uncontrolled release and poor responsiveness to pathological cues. Here, we report a nanoparticle-cross-linked hydrogel that integrates structural integrity with environment-triggered delivery. We utilized self-assembled epigallocatechin gallate (EGCG)-tobramycin (TOB) nanoparticles as dynamic cross-linkers within a phenylboronic acid-modified gelatin network. The engineered system provides dual-stage responsiveness: the hydrogel disassembles under the hallmark hyperglycemic and acidic conditions of diabetic wounds, releasing the nanoparticles, which then dissociate under acidity to synchronize drug release. Such sequential disassembly acts as a synergistic "one-two punch," allowing EGCG to scavenge ROS and remodel the inflammatory microenvironment, while TOB provides prolonged antibacterial action. In vivo, the system significantly reduced bacterial load, accelerated epithelial regeneration, and promoted high-quality wound healing. By seamlessly coupling nanocontrolled release with microenvironmental sensing, we present a precision-engineered platform for the synergistic treatment of recalcitrant diabetic wounds.
Its unique integration of the multi-dynamic network and intrinsic bioactivity endows the hydrogel with adaptability and microenvironment-regulating capabilities, offering a promising strategy for burn wound management.
Haoping Wang, Yi Guo, Lan Zhang et al.· International Journal of Bio...· 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
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