Development of a Photothermal-Responsive Oxygen Release Hydrogel for Accelerating Wound Healing

Jan 24, 2025

Editor: Nina

This study presents the development of a photothermal-response oxygen release platform based on a hydrogel, designed to accelerate wound healing by providing controlled oxygen release and reducing inflammation through NIR-triggered nanoparticle activation.

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Research Question  

The study addresses the challenge of providing continuous and controllable oxygen around injured tissue while inhibiting inflammation, which is crucial for effective wound healing.

Research Design and Strategy  

The researchers designed a composite hydrogel system, incorporating photothermal response-assisted strategies for oxygen release, to enhance wound healing by simultaneously managing oxygen supply and inflammation.

Method  

The methodology involved the creation of a polydopamine-hyaluronic acid hydrogel loaded with calcium peroxide-indocyanine green nanoparticles, combined with lauric acid and manganese dioxide, to achieve controlled oxygen release in response to near-infrared (NIR) light.

Key Results  

The study found that the developed hydrogel significantly accelerated wound healing in a rat model, with complete wound closure observed in the experimental group treated with NIR irradiation. The hydrogel enabled controllable oxygen release and reduced inflammation, as confirmed through histological analysis.

Significance of the Research  

This research offers a novel approach to chronic wound treatment, integrating oxygen supply with anti-inflammatory mechanisms, potentially transforming wound healing methodologies in clinical settings.

Introduction  

Wound healing is a complex biological process where oxygen plays a pivotal role. Despite advances, hypoxic conditions around wounds remain a challenge, exacerbated by factors such as disrupted microcirculation and the presence of wound dressings. This study introduces an innovative photothermal-response oxygen release platform that addresses these challenges by providing a continuous supply of oxygen while concurrently mitigating inflammation, a key factor in the wound healing process.

Research Team and Objective

The research was conducted by Chunyang Li, Xiaojun He, Qingfeng Li, Mingzhi Lv, Jianliang Shen, Lin Jin, and Deyan He at Lanzhou University and Wenzhou Medical University. Their study, titled “A photothermal-response oxygen release platform based on a hydrogel for accelerating wound healing,” was published in NPG Asia Materials. The objective was to create an effective treatment for chronic wounds through the integration of oxygen release and anti-inflammatory strategies.

Experimental Process

Outline:

1.Synthesis of CaO2 Nanoparticles

2. Fabrication of CaO2-ICG@LA Nanoparticles

3. Synthesis of CaO2-ICG@LA@MnO2 Nanoparticles

4. Fabrication of PDA-HA Hydrogel

5. Evaluation of Photothermal Performance

1. Synthesis of CaO2 Nanoparticles

  • Key Steps: The CaO2 nanoparticles were synthesized using a chemical precipitation method. Initially, a 2 mol/L solution of calcium chloride (CaCl2) was mixed with methanol and hydrogen peroxide (H2O2). Ammonia solution was then added to initiate the reaction, resulting in the formation of CaO2 nanoparticles.
    • The product was collected by centrifugation, washed with ethanol, and dried in a vacuum oven at 60°C for 12 hours.
  • Results and Key Data: The CaO2 nanoparticles had a particle size range of 50–150 nm, as determined by TEM imaging. The XRD patterns confirmed that the nanoparticles had a tetragonal structure.

Figure 1. XRD image of CaO2 nanoparticles

  • Significance of the Results: The CaO2 nanoparticles are known for their high oxygen generation capacity, which is crucial for the wound healing process. Their controlled oxygen release potential makes them ideal for tissue engineering applications.
  • Key Innovations: This method provided a scalable approach to synthesize CaO2 nanoparticles with high oxygen generation efficiency, addressing the challenge of maintaining oxygen supply in hypoxic wound environments.

2. Fabrication of CaO2-ICG@LA Nanoparticles

  • Key Steps: To improve the controlled release of oxygen, CaO2 nanoparticles were mixed with indocyanine green (ICG) and lauric acid (LA). The mixture was stirred and sonicated to ensure proper dispersion.
    • The ICG was incorporated to introduce photothermal properties, while LA served to coat the nanoparticles, controlling their interaction with water.
    • The final product was separated by centrifugation, washed with methanol, and dried.
  • Results and Key Data: The CaO2-ICG@LA nanoparticles exhibited a core-shell structure with CaO2 at the core, ICG on the surface, and LA as the outer coating.

Figure 2. TEM image of CaO2-ICG@LA nanoparticles

  • Significance of the Results: The coating with LA helps to modulate the oxygen release rate, while ICG introduces photothermal properties that can be activated by near-infrared (NIR) laser irradiation.
  • Key Innovations: This step successfully integrated both oxygen-generating and photothermal properties into one nanoparticle, paving the way for controlled oxygen release upon laser activation.

3. Synthesis of CaO2-ICG@LA@MnO2 Nanoparticles

  • Key Steps: Manganese dioxide (MnO2) nanoparticles were mixed with the previously fabricated CaO2-ICG@LA nanoparticles in an ethanol solution. After ultrasonication, the mixed solution was dried at room temperature to form the CaO2-ICG@LA@MnO2 nanoparticles.
  • Results and Key Data: The MnO2 nanoparticles enhanced the oxygen release by catalyzing the decomposition of H2O2 into oxygen.
    • The final CaO2-ICG@LA@MnO2 nanoparticles displayed the expected morphology, with well-dispersed MnO2 integrated into the nanoparticle structure.
  • Significance of the Results: The MnO2 nanoparticles served as a catalyst to accelerate oxygen release, improving the overall efficiency of the system and enhancing its potential for wound healing applications.
  • Key Innovations: The incorporation of MnO2 represents a novel approach to increase the oxygen release rate in a controlled manner, addressing the burst-release challenge of CaO2 nanoparticles.

4. Fabrication of PDA-HA Hydrogel

  • Key Steps: The hydrogel was fabricated by polymerizing dopamine (DA) in the presence of hyaluronic acid (HA) using ammonium persulfate (AP) as an oxidant.
    • The PDA-HA hydrogel was formed through the polymerization of DA, creating a stable, bioadhesive network suitable for wound healing.
    • The CaO2-ICG@LA@MnO2 nanoparticles were incorporated into the hydrogel to form the composite nanocomposite hydrogel (NC hydrogel).
  • Results and Key Data: The resulting hydrogel exhibited excellent bioadhesion, flexibility, and self-healing properties, making it suitable for wound dressing applications.

Figure 3. bioadhesion

  • Significance of the Results: The hydrogel provided a platform for embedding the oxygen-releasing nanoparticles, while also supporting tissue adhesion and healing.
  • Key Innovations: The dual-network structure of the hydrogel, combined with the nanoparticle incorporation, improved its mechanical and healing properties, offering a more effective dressing for wounds.

5. Evaluation of Photothermal Performance

  • Key Steps: The photothermal performance of the NC hydrogel was tested under 808 nm NIR laser irradiation. The hydrogel’s temperature response was monitored at different laser power densities and irradiation times.
  • Results and Key Data: The hydrogel showed a temperature increase with prolonged exposure to the NIR laser. The photothermal stability was confirmed over multiple cycles, demonstrating its potential for sustained photothermal therapy.

Figure 4. Heating curves of the PDA-HA hydrogel for 5 on-off cycles under 808 nm laser irradiation (1.0 W cm−2 )

  • Significance of the Results: The photothermal response is crucial for activating the photothermal properties of ICG, enabling controlled oxygen release and inflammation regulation at the wound site.
  • Key Innovations: The combination of NIR-responsive photothermal effects with oxygen release capabilities presents a new approach for treating chronic wounds by modulating both oxygen supply and inflammation

Conclusion

The study demonstrated that the developed CaO2-ICG@LA@MnO2 composite hydrogel effectively facilitates wound healing through controlled oxygen release and inflammation management. The results highlight the potential for this innovative approach in treating chronic wounds, although limitations such as the need for further biocompatibility studies and clinical trials were acknowledged. Future research should explore the long-term effects of this hydrogel and its application in various wound types and conditions.

Overall, this research marks a significant advancement in wound healing technologies, paving the way for improved therapeutic strategies in clinical practice.

Reference:

Li, Chunyang, et al. “A photothermal-response oxygen release platform based on a hydrogel for accelerating wound healing.” NPG Asia Materials 15.1 (2023): 3.