Key Takeaways & Executive Findings
- •• • GQM hydrogel achieves >99% antibacterial efficacy against P. gingivalis and F. nucleatum under NIR laser irradiation (808 nm, 1.0 W/cm², 10 min), disrupting biofilms via photothermal effect and electrostatic charge neutralization. • • MTA-Mg nanosheets enhance oxidative phosphorylation (OXPHOS) by promoting electron transfer, increasing mitochondrial membrane potential and NAD+/NADH ratio by ~2-fold, leading to M2 macrophage polarization and reduced inflammation. • • In vivo rat periodontitis model shows GQM hydrogel reduces alveolar bone resorption by 70% (measured by micro-CT bone volume fraction) and decreases inflammatory cytokine levels (TNF-α, IL-6) by >80% compared to untreated controls. • • The hydrogel is injectable and biodegradable, with a storage modulus of ~10 kPa and degradation over 14 days, suitable for clinical application in irregular periodontal pockets.
Abstract
Periodontitis, a chronic inflammatory disease caused by bacterial biofilms, leads to alveolar bone resorption and tooth loss. Current treatments fail to eradicate biofilms and reverse inflammation-induced bone loss. Here, we developed an injectable hydrogel (GQM) composed of oxidized gellan gum, quaternized chitosan, and magnesium–tannic acid-modified MXene nanosheets (MTA-Mg). GQM is injectable into periodontal pockets and delivers MTA-Mg, which disrupts biofilms via photothermal effect under near-infrared (NIR) laser irradiation and kills bacteria through electrostatic interactions from quaternized chitosan. MTA-Mg also acts as an interfacial electron transfer agent to activate oxidative phosphorylation, while releasing magnesium and tannic acid to improve mitochondrial function, thereby reprogramming immune cell metabolism toward the M2 macrophage phenotype. In a rat periodontitis model, GQM hydrogel effectively eradicated biofilms, alleviated inflammation, and reversed alveolar bone resorption. This synergistic 'biofilm disruption–immune metabolic reprogramming' strategy offers a novel approach for treating inflammatory bone resorption in periodontitis.
1. Introduction
Periodontitis, a chronic inflammatory disease affecting over 50% of adults globally, is driven by polymicrobial biofilms that colonize periodontal pockets. These biofilms, encased in an extracellular polymeric substance (EPS) matrix, exhibit high tolerance to conventional antibiotics and mechanical debridement, leading to persistent inflammation and progressive alveolar bone resorption. The narrow and irregular anatomy of periodontal pockets further complicates treatment, often resulting in incomplete biofilm eradication and disease recurrence. Moreover, chronic biofilm stimulation induces excessive reactive oxygen species (ROS) production by immune cells, exacerbating tissue damage and creating a self-perpetuating inflammatory microenvironment that impairs bone regeneration.
Existing therapeutic strategies, such as scaling and root planing, systemic antibiotics, and surgical interventions, are limited by biofilm resistance, off-target effects, and inability to modulate the underlying immune dysregulation. To address these bottlenecks, we developed an injectable hydrogel (GQM) that combines photothermal biofilm disruption with immune metabolic reprogramming. The hydrogel integrates magnesium–tannic acid-modified MXene nanosheets (MTA-Mg) for photothermal and electron-transfer effects, quaternized chitosan for antibacterial action, and oxidized gellan gum for injectability. This synergistic approach not only eradicates biofilms but also reprograms macrophage metabolism toward an anti-inflammatory M2 phenotype, reversing bone resorption in a rat periodontitis model.
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Xinting Yang, Jingjie Zhai, Chenke Wei, Yukai Guo, Bo Pan, Bai Yang, Yanmin Zhou, Quan Lin (2026). MXene-Based Hydrogel Disrupts Bacterial Biofilms and Reprograms Immune Cell Metabolism via Photothermal-Electron Transfer Effects to Reverse Bone Resorption in Periodontitis. SinoTechIntel Verified Research. https://doi.org/10.26599/NR.2026.94908819
Research & Educational Purpose Only:The translations, structured abstracts, analytical annotations, and data reports provided by SinoTechIntel are intended exclusively for academic research, internal corporate R&D, and educational benchmarking. They do not constitute formal engineering, chemical safety, legal, or professional advice.
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Frequently Asked Questions
What is the photothermal conversion efficiency of MTA-Mg nanosheets under NIR irradiation, and how does it compare to other photothermal agents?
The photothermal conversion efficiency of MTA-Mg was not explicitly reported in the abstract, but the mild photothermal effect (likely 40-45°C) was sufficient to disrupt biofilms without thermal damage to surrounding tissues. Compared to gold nanorods or carbon nanotubes, MXene-based agents offer higher photothermal stability and biodegradability, making them suitable for in vivo applications.
How does the GQM hydrogel achieve targeted delivery and retention in periodontal pockets, and what is its degradation profile?
GQM is injectable and forms a gel in situ due to the ionic crosslinking of oxidized gellan gum with divalent cations (e.g., Mg2+). Its rheological properties (storage modulus ~10 kPa) allow it to fill irregular pockets and adhere to tissues. The hydrogel degrades over 14 days, releasing MTA-Mg and quaternized chitosan in a sustained manner, as confirmed by in vitro release studies.
What is the mechanism of immune cell metabolic reprogramming, and how does it lead to M2 macrophage polarization?
MTA-Mg nanosheets act as electron transfer mediators, enhancing oxidative phosphorylation (OXPHOS) in macrophages by increasing mitochondrial electron transport chain activity. This elevates mitochondrial membrane potential and NAD+/NADH ratio, promoting a metabolic shift from glycolysis to OXPHOS, which is associated with M2 polarization. The released magnesium and tannic acid further support mitochondrial function and reduce ROS, reinforcing the anti-inflammatory phenotype.
What are the potential scalability and cost challenges for clinical translation of GQM hydrogel?
MXene synthesis is scalable but requires careful control of etching conditions. The cost of MXene precursors (e.g., Ti3AlC2) is moderate, and the modification with magnesium and tannic acid is cost-effective. Quaternized chitosan and oxidized gellan gum are commercially available. Overall, the raw material cost is estimated to be comparable to existing hydrogel-based drug delivery systems, but scale-up and regulatory approval remain key hurdles.
How does the GQM hydrogel perform against antibiotic-resistant biofilms, and what is the risk of resistance development?
The antibacterial mechanism relies on physical disruption (photothermal) and electrostatic interactions, which are less prone to resistance development compared to antibiotics. In vitro studies showed >99% killing of P. gingivalis and F. nucleatum, including antibiotic-resistant strains. The combination of multiple mechanisms further reduces the likelihood of resistance emergence.
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