Effects and mechanism of cerium-myricetin nanosystem on wound healing in rats with full-thickness burns

Wang Tao; Teng Junfei; Hu Chao; Wan Luyao; Zhang Wei; Bai Xiangyang; Deng Jun; Luo Gaoxing

doi:10.3760/cma.j.cn501225-20260312-00101

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Wang Tao,Teng Junfei,Hu Chao,et al.Effects and mechanism of the cerium-myricetin nanosystem on wound healing in rats with full-thickness burns[J].Chin J Burns Wounds,2026,42(7):1-11.DOI: 10.3760/cma.j.cn501225-20260312-00101.

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Effects and mechanism of cerium-myricetin nanosystem on wound healing in rats with full-thickness burns

doi: 10.3760/cma.j.cn501225-20260312-00101

1.
Institute of Burn Research, State Key Laboratory of Trauma and Chemical Poisoning, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing 400038, China
2.
Department of Dermatology of Jiangbei Campus, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), Chongqing 400020, China

Funds:

National Key Research and Development Program of China 2021YFA1101100

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Corresponding author: Luo Gaoxing, Email: logxw@tmmu.edu.cn
Received Date: 2026-03-12
Available Online: 2026-07-07

Abstract

Abstract

Objective To investigate the effects and mechanism of cerium-myricetin nanosystem (Ce-MYR) on wound healing in rats with full-thickness burns. Methods This study was an experimental study with a grouped design. Ce-MYR was prepared by coordination self-assembly and characterized. Mouse RAW264.7 cells were divided into control group cultured normally, hydrogen peroxide group treated with hydrogen peroxide, and low Ce-MYR group, medium Ce-MYR group, and high Ce-MYR group treated with hydrogen peroxide followed by Ce-MYR at final mass concentrations of 5, 10, and 20 μg/mL, respectively. After 24 h of culture, intracellular reactive oxygen species (ROS) levels were detected using the fluorescent probe method. Mouse bone marrow-derived macrophages (BMDMs) were divided into control group cultured normally, lipopolysaccharide (LPS) group treated with LPS, and Ce-MYR group treated with LPS combined with Ce-MYR. After 24 h of culture, immunofluorescence staining was performed to detect and calculate the percentages of CD86- and CD206-positive areas. Additional mouse BMDMs were divided into LPS group and Ce-MYR group treated as the described above. After 24 h of culture, the protein expressions of heme oxygenase-1 (HO-1), arginase-1 (Arg-1), inducible nitric oxide synthase (iNOS), and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) were detected by Western blotting. The sample size in all the above experiments was 4. Ten 6-week-old male Sprague-Dawley rats were used to establish four full-thickness burn wounds on the back of each rat, which were divided into phosphate-buffered saline (PBS) group and Ce-MYR group according to the random number table method, with 5 rats in each group. PBS or Ce-MYR was subcutaneously injected at the wound margin on post-injury days 0 (immediately), 3, and 6, respectively. The percentages of residual wound area were calculated on post-injury days 3, 7, 14, and 21. On post-injury day 21, the wound tissue of rats was collected to evaluate granulation tissue thickness after hematoxylin-eosin staining, to calculate the type Ⅰ/type Ⅲ collagen ratio after Sirius red-acid fuchsin staining, to count CD31-positive blood vessels after immunohistochemical staining, to determine the percentages of CD86-and CD206-positive areas after immunofluorescence staining, and to detect the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) after enzyme-linked immunosrbent assay. Results After 24 h of culture, the ROS level in RAW264.7 cells in hydrogen peroxide group was significantly higher than that in control group (P<0.05); the ROS level in RAW264.7 cells in medium Ce-MYR group was significantly lower than that in low Ce-MYR group (P<0.05) and significantly higher than that in high Ce-MYR group (P<0.05). After 24 h of culture, the percentage of CD86-positive area in BMDMs in LPS group was significantly higher than that in control group and Ce-MYR group (with both P values <0.05), while the percentage of CD206-positive area in BMDMs in Ce-MYR group was significantly higher than that in control group and LPS group (with both P values <0.001). Compared with those in LPS group, the protein expressions of HO-1 and Arg-1 in BMDMs in Ce-MYR group were significantly increased (P<0.05), whereas the protein expressions of iNOS and NLRP3 were significantly decreased (P<0.05). On post-injury days 3, 7, 14, and 21, the percentages of residual wound area in rats in Ce-MYR group were (87.1±2.4)%, (65.1±2.2)%, (16.6±1.9)%, and (0.5±0.4)%, respectively, which were significantly lower than (101.5±3.5)%, (79.9±3.2)%, (36.2±3.9)%, and (14.5±1.9)% in PBS group (with t values of 7.604, 8.478, 10.193, and 16.166, respectively; P<0.001). On post-injury day 21, compared with those in PBS group, the granulation tissue thickness, type Ⅰ/type Ⅲ collagen ratio, and number of CD31-positive blood vessels in wound tissue of rats in Ce-MYR group were significantly increased (with t values of 5.179, 6.212, and 3.395, respectively, P<0.05). The percentage of CD86-positive area in wound tissue was significantly decreased (t=4.474, P<0.05), whereas the percentage of CD206-positive area was significantly increased (t=4.713, P<0.05). The levels of IL-1β, IL-6, and TNF-α in wound tissue were significantly decreased (with t values of 3.999, 5.040, and 6.023, respectively, P<0.05). Conclusions Ce-MYR may promote macrophage polarization from the M1 phenotype toward the M2 phenotype by reducing ROS levels and enhancing HO-1-related antioxidant responses, in macrophages thereby improving oxidative stress and inflammatory imbalance in rats with full-thickness burn wounds and promoting wound repair.
- Burns,
- Reactive oxygen species,
- Macrophages,
- Cerium-based nanozyme,
- Metal-phenolic network,
- Macrophage polarization,
- Wound repair

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References(38)

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