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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  >  > Accepted Manuscript
Zhang Xiaowei,Xu Shuangyi,Han Yujia,et al.Influence and mechanism of Prussian blue nanoparticles combined with mouse ADSCs on full-thickness skin defect wounds in diabetic mice[J].Chin J Burns Wounds,2026,42(7):1-10.DOI: 10.3760/cma.j.cn501225-20250106-00009.
Citation: Zhang Xiaowei,Xu Shuangyi,Han Yujia,et al.Influence and mechanism of Prussian blue nanoparticles combined with mouse ADSCs on full-thickness skin defect wounds in diabetic mice[J].Chin J Burns Wounds,2026,42(7):1-10.DOI: 10.3760/cma.j.cn501225-20250106-00009.
shu

Influence and mechanism of Prussian blue nanoparticles combined with mouse ADSCs on full-thickness skin defect wounds in diabetic mice

doi: 10.3760/cma.j.cn501225-20250106-00009

  • Department of Burn and Plastic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Northern Jiangsu People's Hospital, Yangzhou 225009, China

Funds:

Jiangsu Provincial Science and Technology Development Program for Traditional Chinese Medicine YB2020086

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  • Corresponding author: Xu Gang, Email: drxugang@126.com
  • Received Date: 2025-01-06
    Available Online: 2026-07-07
    Abstract
  •   Objective  To investigate the influence and mechanism of Prussian blue nanoparticles (PBNPs) combined with mouse adipose-derived mesenchymal stem cells (ADSCs) on full-thickness skin defect wounds in diabetic mice.  Methods  This study was an experimental study using a group design and a repeated-measures design. PBNPs were prepared by hydrothermal synthesis, and their morphology was characterized using transmission electron microscopy. ADSCs were isolated from five male 6–8-week-old Institute of Cancer Research (ICR) mice via collagenase digestion. The cells were divided into control group cultured under routine conditions, high-glucose group cultured with glucose in a final molarity of 30.0 mmol/L, and low-PBNP group and high-PBNP group pretreated with 10 or 20 μg/mL PBNP for 12 h, respectively, followed by the same treatment as in high-glucose group. After 24 h of culture, cell viability was assessed using the cell counting kit-8, the proportion of senescent cells in the cells was detected by β-galactosidase staining, and the protein expression levels of senescence-associated proteins p16 and p21 were determined by Western blotting. Twenty-four male 6–8-week-old ICR mice were used to establish the diabetic model. A full-thickness skin defect wound was then created on the back of each mouse. The injured mice were divided into four groups (with 6 mice in each group) according to the random number table method, including control group with wounds treated with normal saline, ADSC group with wounds treated with normal saline containing 5×106 ADSC (the same cell number below), low-PBNP group and high-PBNP group with wounds treated with normal saline containing ADSC pretreated with 10 and 20 μg/mL PBNP for 12 h, respectively. Wound healing was observed at post-injury day (PID) 0 (immediately), 3, 7, 10, and 14. The percentage of remaining wound area was calculated at post-injury day 3, 7, 10, and 14. At PID 7, the protein expression levels of the cell proliferation markers Ki67 and vascular endothelial growth factor (VEGF) in wound tissue were detected by immunofluorescence method. At PID 14, the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 in wound tissue were determined by enzyme-linked immunosorbent assay.  Results  PBNP exhibited a dispersed regular cubic structure. After 24 h of culture, compared with those in control group, cells in high-glucose group showed a significantly lower cell viability (P<0.05), a significantly higher proportion of senescent cells (P<0.05), and significantly higher protein expression levels of p16 and p21 (P<0.05). Compared with those in high-glucose group, cells in low-PBNP and high-PBNP groups showed significantly higher cell viability (P<0.05), significantly lower proportions of senescent cells (P<0.05), and significantly lower protein expression levels of p16 and p21 (P<0.05). From PID 0 to 14, the wounds in all four groups healed gradually. At PID 3, 7, 10, and 14, the percentages of remaining wound area of mice in high-PBNP group were (75.3±3.1)%, (46.7±2.5)%, (24.0±5.2)%, and (8.0±1.0)%, respectively, all significantly lower than (85.0±2.0)%, (62.7±3.1)%, (46.7±3.8)%, and (19.3±2.1)% in ADSC group (P<0.05). At PID 7, the percentage of remaining wound area of mice in ADSC group was significantly lower than that in control group ((77.3±3.2)%, P<0.05). At PID 7, the protein expression levels of Ki67 and VEGF of cells in ADSC group were significantly higher than those in control group (P<0.05), the protein expression levels of Ki67 of cells in low-PBNP and high-PBNP groups and the protein expression level of VEGF of cells in high-PBNP group were significantly higher than those in ADSC group (P<0.05). At PID 14, compared with those in control group, wound tissue in ADSC group showed a significantly higher expression level of IL-10 (P<0.05) and significantly lower expression levels of TNF-α, IL-1β, and IL-6 (P<0.05); compared with those in ADSC group, wound tissue in low-PBNP and high-PBNP groups showed significantly higher expression levels of IL-10 (P<0.05) and significantly lower expression levels of TNF-α, IL-1β, and IL-6 (P<0.05).  Conclusions  PBNP can alleviate high glucose-induced senescence of mouse ADSCs. Compared with mouse ADSCs alone, the combination of PBNP and mouse ADSCs more effectively promotes cell proliferation and angiogenesis in full-thickness skin defect wounds of diabetic mice, inhibits the release of inflammatory cytokines, and accelerates wound healing.

     

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    • References(37)
  • [1]
    DawiJ,TumanyanK,TomasK,et al.Diabetic foot ulcers: pathophysiology, immune dysregulation, and emerging therapeutic strategies[J].Biomedicines,2025,13(5):1076.DOI: 10.3390/biomedicines13051076.
    [2]
    SunD,GuoK,LiuN,et al.Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis[J/OL].Burns Trauma,2023,11:tkad035[2025-01-06].https://pubmed.ncbi.nlm.nih.gov/38026443/.DOI: 10.1093/burnst/tkad035.
    [3]
    ZhangJ,LiuY,ChenY,et al.Adipose-derived stem cells: current applications and future directions in the regeneration of multiple tissues[J].Stem Cells Int,2020,2020:8810813.DOI: 10.1155/2020/8810813.
    [4]
    CaplanH,OlsonSD,KumarA,et al.Mesenchymal stromal cell therapeutic delivery: translational challenges to clinical application[J].Front Immunol,2019,10:1645.DOI: 10.3389/fimmu.2019.01645.
    [5]
    WangZ,LiH,GuoR,et al.Antioxidants inhibit advanced glycosylation end-product-induced apoptosis by downregulation of miR-223 in human adipose tissue-derived stem cells[J].Sci Rep,2016,6:23021.DOI: 10.1038/srep23021.
    [6]
    唐黎珺,樊亮花,王静荣,等.虾青素对高糖处理的人皮肤成纤维细胞衰老的作用及其机制[J].中华烧伤与创面修复杂志,2025,41(11):1101-1110.DOI: 10.3760/cma.j.cn501225-20250109-00018.
    [7]
    MaZ,DingY,DingX,et al.PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway[J].Cell Death Discov,2023,9(1):424.DOI: 10.1038/s41420-023-01725-2.
    [8]
    BusquetsMA,EstelrichJ.Prussian blue nanoparticles: synthesis, surface modification, and biomedical applications[J].Drug Discov Today,2020,25(8):1431-1443.DOI: 10.1016/j.drudis.2020.05.014.
    [9]
    XuZ,LiuY,MaR,et al.Thermosensitive hydrogel incorporating prussian blue nanoparticles promotes diabetic wound healing via ROS scavenging and mitochondrial function restoration[J].ACS Appl Mater Interfaces,2022,14(12):14059-14071.DOI: 10.1021/acsami.1c24569.
    [10]
    孙宝俊,赵风景,章文锋,等.普鲁士蓝纳米粒对过氧化氢诱导脂肪间充质干细胞凋亡的影响[J].中华实验外科杂志,2023,40(12):2548-2553.DOI: 10.3760/cma.j.cn421213-20230416-00217.
    [11]
    徐双依,龚政,韩雨佳,等.普鲁士蓝纳米粒对经过氧化氢处理的小鼠脂肪间充质干细胞凋亡的作用及其机制[J].中华烧伤与创面修复杂志,2025,41(5):481-490.DOI: 10.3760/cma.j.cn501225-20240525-00197.
    [12]
    Berthiaume FoxKA,GalvinER,Kness-KnezinskisE,et al.Decoding wound healing: cellular insights and technological advances[J].NPJ Biomed Innov,2026,3(1):1.DOI: 10.1038/s44385-025-00046-6.
    [13]
    LinS,WangQ,HuangX,et al.Wounds under diabetic milieu: the role of immune cellar components and signaling pathways[J].Biomed Pharmacother,2023,157:114052.DOI: 10.1016/j.biopha.2022.114052.
    [14]
    ZhangG,SamarawickramaPN,GuiL,et al.Revolutionizing diabetic foot ulcer care: the senotherapeutic approach[J].Aging Dis,2024,16(2):946-970.DOI: 10.14336/AD.2024.0065.
    [15]
    DasariN,JiangA,SkochdopoleA,et al.Updates in diabetic wound healing, inflammation, and scarring[J].Semin Plast Surg,2021,35(3):153-158.DOI: 10.1055/s-0041-1731460.
    [16]
    CaoJ,LiuZC,AnWQ,et al.Optimizing adipose-derived stem cell therapy for diabetic foot ulcers[J].World J Diabetes,2025,16(11):109859.DOI: 10.4239/wjd.v16.i11.109859.
    [17]
    ZhangB,GengH,ZhaoK,et al.FSTL1 aggravates high glucose-induced oxidative stress and transdifferentiation in HK-2 cells[J].Sci Rep,2025,15(1):434.DOI: 10.1038/s41598-024-84462-5.
    [18]
    GonzálezP,LozanoP,RosG,et al.Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections[J].Int J Mol Sci,2023,24(11):9352.DOI: 10.3390/ijms24119352.
    [19]
    Berlanga-AcostaJA,Guillén-NietoGE,Rodríguez-RodríguezN,et al.Cellular senescence as the pathogenic hub of diabetes-related wound chronicity[J].Front Endocrinol (Lausanne),2020,11:573032.DOI: 10.3389/fendo.2020.573032.
    [20]
    HiebertP,WietechaMS,CangkramaM,et al.Nrf2-mediated fibroblast reprogramming drives cellular senescence by targeting the matrisome[J].Dev Cell,2018,46(2):145-161.e10.DOI: 10.1016/j.devcel.2018.06.012.
    [21]
    O'ReillyS,MarkiewiczE,IdowuOC.Aging, senescence, and cutaneous wound healing-a complex relationship[J].Front Immunol,2024,15:1429716.DOI: 10.3389/fimmu.2024.1429716.
    [22]
    ZhangD,LuH,ChenZ,et al.High glucose induces the aging of mesenchymal stem cells via Akt/mTOR signaling[J].Mol Med Rep,2017,16(2):1685-1690.DOI: 10.3892/mmr.2017.6832.
    [23]
    PhamHL,PhamPV.High glucose induces early senescence in adipose-derived stem cells by accelerating p16 and mTOR[J].Biomed Res Ther,2019,6(6):3213-3221.DOI: 10.15419/bmrat.v6i6.548.
    [24]
    ShuklaM, VermaNV, MohantaZ, et al. A review on tunable multi-functional Prussian blue nanoparticles; their promising biological applications & future directions[J]. Coord Chem Rev, 2023, 496:215414. DOI: 10.1016/j.ccr.2023.215414.
    [25]
    ZhangW,HuS,YinJJ,et al.Prussian blue nanoparticles as multienzyme mimetics and reactive oxygen species scavengers[J].J Am Chem Soc,2016,138(18):5860-5865.DOI: 10.1021/jacs.5b12070.
    [26]
    ZhouT,YangX,ChenZ,et al.Prussian blue nanoparticles stabilize SOD1 from ubiquitination-proteasome degradation to rescue intervertebral disc degeneration[J].Adv Sci (Weinh),2022,9(10):e2105466.DOI: 10.1002/advs.202105466.
    [27]
    ChenL,TangS,ZhangJ,et al.Prussian blue nanohybridized multicellular spheroids as composite engraftment for antioxidant bone regeneration and photoacoustic tomography[J].ACS Nano,2024,18(36):24770-24783.DOI: 10.1021/acsnano.3c06835.
    [28]
    HeF,XuP,ZhuZ,et al.Inflammation-responsive hydrogel accelerates diabetic wound healing through immunoregulation and enhanced angiogenesis[J].Adv Healthc Mater,2025,14(5):e2400150.DOI: 10.1002/adhm.202400150.
    [29]
    FotiR,StortiG,PalmesanoM,et al.Senescence in adipose-derived stem cells: biological mechanisms and therapeutic challenges[J].Int J Mol Sci,2024,25(15):8390.DOI: 10.3390/ijms25158390.
    [30]
    刘童君,赵雅洁,胡洁玲,等.衰老相关分泌表型因子在糖尿病衰老干预疗法中的研究进展[J].实用老年医学,2023,37(5):528-531.DOI: 10.3969/j.issn.1003-9198.2023.05.023.
    [31]
    LiC,RenS,YanC,et al.HES1 revitalizes the functionality of aged adipose-derived stem cells by inhibiting the transcription of STAT1[J].Stem Cell Res Ther,2024,15(1):399.DOI: 10.1186/s13287-024-04002-w.
    [32]
    LiX,LiC,ZhangW,et al.Inflammation and aging: signaling pathways and intervention therapies[J].Signal Transduct Target Ther,2023,8(1):239.DOI: 10.1038/s41392-023-01502-8.
    [33]
    García-DomínguezM.Pathological and inflammatory consequences of aging[J].Biomolecules,2025,15(3):404.DOI: 10.3390/biom15030404.
    [34]
    AhmedB,SiH.The aging of adipocytes increases expression of pro-inflammatory cytokines chronologically[J].Metabolites,2021,11(5):292.DOI: 10.3390/metabo11050292.
    [35]
    YinM,ZhangY,YuH,et al.Role of hyperglycemia in the senescence of mesenchymal stem cells[J].Front Cell Dev Biol,2021,9:665412.DOI: 10.3389/fcell.2021.665412.
    [36]
    KhalidKA,NawiAFM,ZulkifliN,et al.Aging and wound healing of the skin: a review of clinical and pathophysiological hallmarks[J].Life (Basel),2022,12(12):2142.DOI: 10.3390/life12122142.
    [37]
    XiaoY,ZhangY,XiaoF.Comparison of several commonly used detection indicators of cell senescence[J].Drug Chem Toxicol,2020,43(2):213-218.DOI: 10.1080/01480545.2018.1551407.
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