Guar gum-based multi-dynamic cross-linked network hydrogel with wound adaptability and microenvironment regulation for the treatment of burn infections.
Jul 2026· International Journal of Biological Macromolecules· pp.
153663
· 0 citations· 54 references
Medicine
TL;DR
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.
Abstract
Burn wounds are often complicated by infection, inflammation, and severe pain. Conventional hydrogel dressings fail to meet the complex demands of infected burn wounds due to poor mechanical compliance and limited biological functions. To overcome these bottlenecks and actively regulate the wound microenvironment, a functionalized guar gum-based hydrogel (GEB-ME) featuring a multi-dynamic cross-linked network was developed. The hydrogel demonstrated conformal filling of irregular wounds and rapid self-healing of its mechanical integrity following damage. Capable of adhering to the wound site and accommodating deformations from external mechanical stress and physiological movement, the hydrogel provided continuous, reliable barrier protection for complex wounds. Furthermore, it exhibited an analgesic effect, effectively eliminated pathogenic bacteria, and scavenged reactive oxygen species generated by oxidative stress. The hydrogel also downregulated the expression of pro-inflammatory cytokines (TNF-α and IL-6) while promoting angiogenesis. Benefiting from its excellent biocompatibility, the hydrogel showed significant therapeutic efficacy in an in vivo model of infected burn 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.
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
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.
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
In clinical wound closure, traditional sutures are cumbersome and prone to causing secondary injury, while existing biological adhesives struggle to balance strong adhesion, high safety, and good adaptability within the complex and variable wound microenvironment. Excessive reactive oxygen species (ROS) and persistent inflammation at the wound site are key factors causing imbalance in the healing microenvironment and delaying repair. To address this, this study designed an in-situ injectable self-healing hydrogel adhesive aimed at actively remodeling the wound healing microenvironment. Constructed through dynamic borate ester crosslinking between phenylboronic acid-modified, oxidized-hyaluronic acid and poly(vinyl alcohol) (OHA-PBA/PVA), this material not only exhibits rapid gelation, strong tissue adhesion, and self-healing capabilities to stabilize the physical microenvironment, but also incorporates phenylboronic acid groups that scavenge ROS, thereby alleviating the oxidative stress microenvironment. In a rat full-thickness skin incision model, this hydrogel achieved wound closure comparable to sutures. Mechanistically, it alleviates wound oxidative stress, modulates the immune microenvironment (reducing TNF-α and promoting M2 macrophage polarization), and guides the regenerative microenvironment (promoting organized collagen deposition). This study provides an alternative strategy for actively modulating multiple healing microenvironments through material design to promote high-quality wound repair. STATEMENT OF SIGNIFICANCE: Current clinical wound closure materials face a fundamental challenge: achieving strong tissue adhesion while actively regulating the complex, multi-dimensional microenvironment that governs wound healing. This study addresses this gap by developing an injectable, self-healing hydrogel adhesive (OHA-PBA/PVA) that orchestrates wound repair through three aspects of microenvironment regulation. The hydrogel acts through three mechanisms: (I) stabilizing the physical microenvironment via rapid gelation and strong adhesion; (II) purifying the biochemical microenvironment by scavenging ROS; and (III) modulating the immune microenvironment to promote M2 polarization, reduce TNF‑α, and enhance collagen deposition and angiogenesis. This multidimensional approach achieves wound closure comparable to sutures with reduced inflammation, offering a promising strategy for high-quality tissue regeneration.
Fengya Jing, Tao Liu, Anbei Chen et al.· Acta Biomaterialia· 0 citations
Infected burn wounds are characterized by bacterial invasion, oxidative stress, and persistent inflammation, which severely impair tissue regeneration. Herein, we report a crosslinker-free, hydrogen-bonded cationic guar gum hydrogel (CBBM) co-loaded with berberine (BBR) and MnO2-coated black phosphorus nanosheets (BPNS@MnO2) for the microenvironment-adaptive treatment of infected burn wounds. The dynamic guar gum network endowed the hydrogel with injectability, self-healing ability, and conformal adaptability. BPNS@MnO2 exhibited pH-dependent enzyme-like activities, including OXD-like antibacterial activity under acidic conditions and SOD-/CAT-like ROS-scavenging activity under near-neutral conditions and endowed the hydrogel with NIR-triggered photothermal responsiveness. Moreover, NIR irradiation further enhanced the antibacterial efficacy and moderately enhanced BBR release from the hydrogel. In vitro, CBBM combined with NIR irradiation achieved potent antibacterial efficacy against S. aureus and E. coli under the tested conditions and reduced intracellular ROS levels. In vivo, the CBBM + NIR treatment accelerated infected burn wound healing, achieving a wound closure rate of 97.53 ± 2.01% by day 14, accompanied by reduced inflammation, enhanced collagen deposition, and increased expression of the angiogenesis-related markers VEGF and CD31. These results demonstrate that the CBBM hydrogel is a promising multifunctional guar gum-based dressing for infected burn wound healing by integrating local drug delivery, catalytic regulation, and photothermal activation.
Ziyi Zhao, Yanxiang Sang, Benyan Zheng et al.· International Journal of Bio...· 0 citations
The diabetic-infected wound microenvironment, marked by elevated reactive oxygen species (ROS) levels, ongoing inflammation, and defective angiogenesis, interferes with the normal wound healing cascade and contributes to delayed and treatment-resistant repair. However, most existing wound dressings lack the capability to dynamically adapt to these spatiotemporally evolving conditions. Herein, a smart and microenvironment-programmable PVH-ST hydrogel is developed to achieve phased and spatiotemporally coordinated regulation of diabetic-infected wound healing. The hydrogel is engineered by integrating strontium (Sr)-tannic acid (ST) nanoparticles into a polyvinyl alcohol (PVA) and hyaluronic acid (HA) matrix through a boric acid-mediated multilevel dynamic crosslinking network, endowing the system with mechanical robustness suitable for daily motion. Upon wound occurrence, the PVH-ST hydrogel rapidly induces hemostasis and establishes a bioactive provisional matrix. In response to the ROS-enriched infected microenvironment, the dynamic borate bonds undergo on-demand dissociation, triggering controlled release of ST nanoparticles. Released ST nanoparticles integrate antibacterial and antioxidant functions and reduce inflammatory burden via modulation of NF-κB signaling and skewing macrophages toward an M2 pro-regenerative state. Concurrently, the sustained release of Sr2+ ions activates VEGF-associated angiogenic signaling and epithelialization pathways, thereby promoting vascularization and epithelial reconstruction for diabetic-infected wounds.
Aihong Chen, Xiaoran Liu, Xiaoqiang Wang et al.· Advanced Healthcare Material...· 0 citations