Tow-Int Tech Facilitates Research on Plateau Wound Healing: The Breakthrough Journey of a Novel Hydrogel Bandage

Rui Lei and others developed an injectable hydrogel bandage for plateau hypoxic wounds, which can improve healing and offer new treatment ways.

Wound healing in plateau areas is a major challenge in the medical field. Traditional wound treatment methods have poor efficacy in the special environment of plateaus. Recently, researchers such as Rui Lei and Mingbao Gu wrote the paper "Lipoic Acid/Trometamol Assembled Hydrogel as Injectable Bandage for Hypoxic Wound Healing at High Altitude", which was published on relevant platforms. This study aimed to develop an injectable hydrogel bandage suitable for hypoxic wounds in plateau areas and explore its performance and molecular mechanisms in promoting wound healing. It was found that this hydrogel bandage could effectively improve the wound healing situation, providing new solutions and research directions for wound treatment in plateau areas.

1. Research Background

Wound healing in plateau areas is difficult. The harsh climate environment with low air pressure, thin oxygen, cold, and the unique geographical environment of plateaus that alters the physiological functions and metabolism of the human body lead to problems such as fat liquefaction, wound hematoma, and non - healing of wounds. Severe hypoxia is one of the important factors affecting wound healing in plateau areas. Developing bandages that can supplement oxygen to promote wound healing has great clinical and economic value. α - Lipoic acid (LA) has received attention in biomedical applications. However, the poly(lipoic acid) (PLA) hydrogel formed by its polymerization is difficult to inject due to its high viscosity and strong adhesion. Developing an injectable PLA - based hydrogel bandage is highly challenging.

2. Experimental Methods

2.1 Experimental Animals and Grouping

SD rats were selected for the experiment and divided into three groups: the GEL group, where the wound was injected with the assembled hydrogel; the GEL + NIR group, where the wound was injected with the assembled hydrogel and then irradiated with near - infrared (NIR); and the BLANK group, where the wound was only treated with hemostasis.

2.2 Establishment of a High - Altitude Trauma Model

Model - making method: In an animal experiment low - pressure oxygen environment control system, anesthetized, shaved, and disinfected SD rats had three 2 - cm - long incisions created on their backs to establish a wound model.

2.3 Detection Indicators

Hydrogel - related performance indicators: A rheometer was used to test the modulus - frequency relationship, strain scan, viscosity change with shear rate, and self - healing behavior of the hydrogel. Density functional theory was used to study the structure and binding energy of the complexes formed by LA and trometamol. The photothermal conversion performance of the hydrogel was tested. Tensile tests were carried out to obtain the fracture strain, elastic modulus, and toughness of the hydrogel. Lap - shear tests were conducted to evaluate the adhesion performance of the hydrogel, and the oxygen - generating ability of the hydrogel was detected.

 Wound - healing - related indicators: H&E and Masson staining were performed on the wounds to observe histological changes. Immunofluorescence staining was used to detect the expression of hypoxia - inducible factor - 1α (HIF - 1α), interleukin - 1β (IL - 1β), and interleukin - 4 (IL - 4) in the wounds.

2.4 Statistical Analysis

Each measurement was based on the repeated analysis of at least three independent experiments. Quantitative results were expressed as mean ± standard deviation. One - way analysis of variance (ANOVA) was used to reveal statistical differences, and p < 0.05 was considered statistically significant.

3. Experimental Results

Hydrogel Gelation and Performance: LA and trometamol could rapidly gel within 5 minutes at room temperature at a specific molar ratio. The addition of Ce³⁺ could accelerate the gelation to within 2 minutes. The hydrogel with the addition of DA and g-C₃N₄ nanosheets had a photothermal function. After NIR irradiation, LA polymerized, and the mechanical and adhesion properties of the hydrogel were enhanced.

 Mechanical Properties: Ce³⁺ could accelerate the polymerization of LA and form a physical network. At low contents, it enhanced the mechanical properties of the hydrogel, while at high contents, it decreased them. DA participated in the polymerization of LA. At low contents, its effect on the mechanical properties was complex, and at high contents, it increased the elastic modulus and toughness and decreased the fracture strain. g-C₃N₄ nanosheets could enhance the mechanical properties of the hydrogel.

 Adhesion Properties: The GEL(LA/DA/Ce³⁺/g-C₃N₄) bandage had strong adhesion to various substrates and tissues. Its adhesion strength was affected by the contents of Ce³⁺, DA, and g-C₃N₄ nanosheets. DA could improve the adhesion stability and long - term effectiveness.

 Wound - Healing Effect: The GEL(LA/DA/Ce³⁺/g-C₃N₄) bandage combined with NIR irradiation could effectively promote wound healing, reduce the expression of HIF - 1α, regulate the expression of inflammatory factors, and create a microenvironment conducive to wound healing.

4. Research Conclusions

LA could rapidly gel with the assistance of trometamol to form an elastic hydrogel, which had injectability and plasticity. NIR irradiation could trigger the polymerization of LA and enhance the cohesion of the hydrogel. The hydrogel bandage containing Ce³⁺, DA, and PDA - coated g-C₃N₄ had good mechanical and adhesion properties and could effectively promote wound healing in a low - pressure oxygen environment, providing a new option for wound treatment in plateau areas.

5. A Variety of Scientific Research Equipment was Used in the Research Process.  

5.1 Rheometer

It was used to test the rheological properties of the hydrogel. The gelation time was determined by observing that the hydrogel solution did not flow when inverted. Frequency sweeps were performed to test the modulus - frequency relationship of the hydrogel. Strain sweeps were carried out to analyze the performance changes of the hydrogel under different strains. The shear - thinning behavior of the hydrogel was tested, and the self - healing behavior of the hydrogel was evaluated.

5.2 Infrared Thermal Imager

It was used to test the photothermal conversion performance of the hydrogel. During the 10 - minute continuous irradiation of hydrogel samples with different dopamine concentrations by an 808 - nm near - infrared laser, the temperature changes and thermal images of the hydrogel were recorded to evaluate its photothermal effect.

5.3 Universal Testing Machine

It was used to perform tensile tests on the hydrogel. By analyzing the stress - strain curve, parameters such as the fracture strain and elastic modulus of the hydrogel were obtained, and the toughness of the hydrogel was calculated.

5.4 Microplate Reader

In the in - vitro biocompatibility test, it was used to measure the absorbance of cell culture wells at 450 nm. After the CCK - 8 reagent reacted with the cells, the microplate reader detected the absorbance to evaluate the effect of the hydrogel on cell proliferation and thus judge the biocompatibility of the hydrogel.

5.5 Invered Fluorescence Microscope

Used in conjunction with the LIVE/DEAD viability/cytotoxicity kit, it was used to observe the viability of cells. In the in - vitro biocompatibility test, the cells co - cultured with the hydrogel were stained, and the live cells (green fluorescence) and dead cells (red fluorescence) were observed under the inverted fluorescence microscope to intuitively evaluate the cytotoxicity of the hydrogel on cells.

5.6 Animal Experiment Low - Pressure Oxygen Environment Control System (ProOx - 811, Tow - Int TECH)

It was used to simulate the low - oxygen environment of plateaus, raise and experiment on SD rats. In the in - vivo experiment of wound healing, a low - oxygen environment was created in this system to study the effect of the hydrogel bandage on wound healing under similar low - oxygen conditions in plateau areas.

This study used the animal experiment hypobraic oxygen environment control system (Tow-Int Tech):

This equipment can simulate an altitude range of 0 - 12,000 meters. The system can automatically complete the processes of depressurization, pressure stabilization, and pressurization. It can accurately control the altitude rise rate, the maintained altitude, the duration, and the altitude descent rate. It can monitor temperature, humidity, oxygen concentration, oxygen partial pressure, carbon dioxide concentration, the pressure inside the chamber, and the simulated altitude. It has a data export function, which can directly store data on a USB flash drive and be read on a computer. It is equipped with a drip - proof special water bottle to avoid dripping during the experiment with a regular water bottle, meeting various experimental requirements.

This equipment can be applied to simulate common acute high - altitude diseases, such as high - altitude cerebral edema, high - altitude pulmonary edema, and high - altitude heart disease. It can also simulate chronic high - altitude diseases, such as polycythemia and cardiovascular diseases.

Reference

Lei R, Gu M, Li J, et al. Lipoic acid/trometamol assembled hydrogel as injectable bandage for hypoxic wound healing at high altitude[J]. Chemical Engineering Journal, 2024, 489: 151499.

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