Photothermal MXene-Embedded Tannin-Eu³⁺ Particles as In Situ Bacterial Vaccines for Seawater-Immersed Infected Wounds

Academic Background

Seawater-immersed wounds are prone to severe infections due to the low temperature, high salinity, and bacteria-rich environment, which hinder wound healing. Traditional antibacterial strategies often fail to provide long-term anti-infection effects or effectively promote wound healing. To address this issue, researchers have developed a novel multifunctional wound dressing aimed at enhancing resistance to seawater-immersed wound infections by killing bacteria and delivering bacterial antigens in situ. This study proposes a strategy based on MXene-embedded tannic acid-europium (M@TA-Eu) particles, which utilize photothermal effects to kill bacteria and form in situ bacterial vaccines, thereby accelerating wound healing and providing long-lasting anti-infection effects.

Source of the Paper

This paper was co-authored by Zhentao Li, Ting Song, Yanpeng Jiao, Zijing Zhu, Yang Liao, and Zonghua Liu, affiliated with the Department of Materials Science and Engineering, Department of Biomedical Engineering at Jinan University, and the Department of Laboratory Medicine at the General Hospital of Southern Theatre Command of PLA. The paper was published online on December 27, 2024, in the journal Bio-design and Manufacturing, with the DOI 10.1631/bdm.2300327.

Research Process and Results

1. Material Preparation and Characterization

a) Preparation of MXene

Researchers first etched Ti₃AlC₂ powder with hydrofluoric acid (HF) to prepare Ti₃C₂ MXene. Subsequently, the MXene was further oxidized using tetrapropylammonium hydroxide (TPAOH) solution, and MXene powder was obtained through freeze-drying. The layered structure and monolayer/few-layer dispersion state of MXene were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD).

b) Preparation of M@TA-Eu Particles

MXene powder was added to a tannic acid (TA) solution, followed by ultrasonic treatment and stirring. Europium (Eu³⁺) solution was then added, and the pH was adjusted to 8.5. Finally, M@TA-Eu particles were obtained through centrifugation and freeze-drying. The morphology and chemical properties of the particles were characterized in detail using SEM, Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and thermogravimetric analysis (TGA).

2. Photothermal Effect and Antioxidant Activity

a) Photothermal Effect

The introduction of MXene significantly enhanced the photothermal response of M@TA-Eu particles. Under 808 nm near-infrared (NIR) light irradiation, the temperature of the particle solution rapidly increased within 30 seconds, demonstrating efficient photothermal conversion. The photothermal effect not only killed bacteria but also promoted the recruitment of antigen-presenting cells, enhancing the efficacy of vaccination.

b) Antioxidant Activity

The phenolic hydroxyl groups of tannic acid (TA) endowed M@TA-Eu particles with excellent antioxidant properties. Experiments showed that the particles exhibited significant scavenging ability against DPPH radicals, H₂O₂, and superoxide anions (·O₂⁻), and effectively cleared intracellular reactive oxygen species (ROS), mitigating oxidative stress-induced cell damage.

3. Cytocompatibility and Antibacterial Performance

a) Cytocompatibility

M@TA-Eu particles demonstrated good cytocompatibility with human umbilical vein endothelial cells (HUVECs) and mouse fibroblasts (L929). Low-concentration particles effectively promoted cell proliferation, while high-concentration particles exhibited dose-dependent cytotoxicity.

b) Antibacterial Performance

M@TA-Eu particles exhibited significant antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Under NIR irradiation, the antibacterial effect of the particles was further enhanced, effectively killing bacteria and disrupting their cell membrane structure.

4. In Vivo Wound Healing Experiments

a) Wound Healing

Researchers established a Sprague-Dawley rat model of seawater-immersed infected wounds and treated them with M@TA-Eu particles. Experimental results showed that NIR-assisted M2@TA-Eu particles significantly accelerated wound healing, inhibited inflammatory responses, and promoted vascular regeneration and collagen deposition.

b) Bacterial Colonization

Three days after wound treatment, NIR-assisted M2@TA-Eu particles significantly reduced bacterial colonization at the wound site, demonstrating strong antibacterial effects.

5. In Situ Vaccine Efficacy Analysis

a) Antigen Presentation and Dendritic Cell Maturation

NIR-assisted M2@TA-Eu particles significantly promoted the maturation and antigen presentation of dendritic cells (DCs), enhancing humoral immune responses.

b) Antibody Production and Cytokine Secretion

Seven days after vaccination, NIR-assisted M2@TA-Eu particles induced high levels of bacterium-specific IgG antibodies and promoted the secretion of cytokines (e.g., TNF-α, IFN-γ, IL-6, and IL-4), demonstrating strong immune activation effects.

c) Long-Term Antibody Levels

Forty days after vaccination, NIR-assisted M2@TA-Eu particles maintained high levels of bacterium-specific IgG antibodies, demonstrating long-lasting anti-infection effects.

Conclusions and Significance

This study developed a multifunctional wound dressing based on MXene-embedded tannic acid-europium particles, which utilize photothermal effects to kill bacteria and form in situ bacterial vaccines, significantly accelerating the healing of seawater-immersed infected wounds and providing long-lasting anti-infection effects. This research not only offers a new therapeutic strategy for complex and refractory infected wounds but also provides important theoretical and experimental foundations for the design and development of multifunctional wound dressings.

Research Highlights

1. Multifunctionality: M@TA-Eu particles integrate photothermal effects, antioxidant properties, pro-angiogenesis, and antigen presentation, comprehensively promoting wound healing.
2. In Situ Vaccines: The formation of in situ vaccines through photothermal effects provides long-lasting anti-infection effects.
3. Efficient Antibacterial Activity: NIR-assisted M2@TA-Eu particles rapidly kill bacteria, significantly reducing bacterial colonization at wound sites.
4. Long-Term Immune Memory: NIR-assisted M2@TA-Eu particles induce long-term bacterium-specific IgG antibodies, demonstrating durable anti-infection effects.

This research provides new insights and methods for the treatment of seawater-immersed infected wounds, holding significant scientific and practical value.