Email Alerts
RSS
Volume 39 Issue 2
Feb.  2023
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2023  >  39(2): 132-140
Li L,Bai N,Fu YJ,et al.Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears[J].Chin J Burns Wounds,2023,39(2):132-140.DOI: 10.3760/cma.j.cn501225-20221020-00463.
Citation: Li L,Bai N,Fu YJ,et al.Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears[J].Chin J Burns Wounds,2023,39(2):132-140.DOI: 10.3760/cma.j.cn501225-20221020-00463.
shu

Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears

doi: 10.3760/cma.j.cn501225-20221020-00463
  • 1.

    Linyi People's Hospital, Linyi 276037, China

  • 2.

    Linyi Cancer Hospital, Linyi 276034, China

Funds:

General Program of Shandong Natural Science Foundation ZR2021MH338

General Program of Shandong Traditional Chinese Medicine Science and Technology Project 2020M170

More Information
    Abstract
  •   Objective  To investigate the influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears, and to analyze the related mechanism.  Methods  Experimental research methods were adopted. The complete fat pads on the back of 42 male New Zealand white rabbits aged 2 to 3 months were cut to prepare adipose stem cell matrix gel, and a full-thickness skin defect wound was established on the ventral side of each ear of each rabbit. The left ear wounds were included in adipose stem cell matrix gel group (hereinafter referred to as matrix gel group), and the right ear wounds were included in phosphate buffer solution (PBS) group, which were injected with autologous adipose stem cell matrix gel and PBS, respectively. The wound healing rate was calculated on post injury day (PID) 7, 14, and 21, and the Vancouver scar scale (VSS) scoring of scar tissue formed on the wound (hereinafter referred to as scar tissue) was performed in post wound healing month (PWHM) 1, 2, 3, and 4. Hematoxylin-eosin staining was performed to observe and measure the histopathological changes of wound on PID 7, 14, and 21 and the dermal thickness of scar tissue in PWHM 1, 2, 3, and 4. Masson staining was performed to observe the collagen distribution in wound tissue on PID 7, 14, and 21 and scar tissue in PWHM 1, 2, 3, and 4, and the collagen volume fraction (CVF) was calculated. The microvessel count (MVC) in wound tissue on PID 7, 14, and 21 and the expressions of transforming growth factor β1 (TGF-β1) and α smooth muscle actin (α-SMA) in scar tissue in PWHM 1, 2, 3, and 4 were detected by immunohistochemical method, and the correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group was analyzed. The expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in wound tissue were detected by enzyme-linked immunosorbent assay on PID 7, 14, and 21. The number of samples at each time point in each group was 6. Data were statistically analyzed with analysis of variance for repeated measurement, analysis of variance for factorial design, paired sample t test, least significant difference test, and Pearson correlation analysis.  Results  On PID 7, the wound healing rate in matrix gel group was (10.3±1.7)%, which was close to (8.5±2.1)% in PBS group (P>0.05). On PID 14 and 21, the wound healing rates in matrix gel group were (75.5±7.0)% and (98.7±0.8)%, respectively, which were significantly higher than (52.7±6.7)% and (90.5±1.7)% in PBS group (with t values of 5.79 and 10.37, respectively, P<0.05). In PWHM 1, 2, 3, and 4, the VSS score of scar tissue in matrix gel group was significantly lower than that in PBS group (with t values of -5.00, -2.86, -3.31, and -4.45, respectively, P<0.05). Compared with the previous time point within the group, the VSS score of scar tissue at each time point after wound healing in the two groups was significantly increased (P<0.05), except for PWHM 4 in matrix gel group (P>0.05). On PID 7, the granulation tissue regeneration and epithelialization degree of the wounds between the two groups were similar. On PID 14 and 21, the numbers of fibroblasts, capillaries, and epithelial cell layers in wound tissue of matrix gel group were significantly more than those in PBS group. In PWHM 1, 2, 3, and 4, the dermal thickness of scar tissue in matrix gel group was significantly thinner than that in PBS group (with t values of -4.08, -5.52, -6.18, and -6.30, respectively, P<0.05). Compared with the previous time point within the group, the dermal thickness of scar tissue in the two groups thickened significantly at each time point after wound healing (P<0.05). Compared with those in PBS group, the collagen distribution in wound tissue in matrix gel group was more regular and the CVF was significantly increased on PID 14 and 21 (with t values of 3.98 and 3.19, respectively, P<0.05), and the collagen distribution in scar tissue was also more regular in PWHM 1, 2, 3, and 4, but the CVF was significantly decreased (with t values of -7.38, -4.20, -4.10, and -4.65, respectively, P<0.05). Compared with the previous time point within the group, the CVFs in wound tissue at each time point after injury and scar tissue at each time point after wound healing in the two groups were significantly increased (P<0.05), except for PWHM 1 in matrix gel group (P>0.05). On PID 14 and 21, the MVC in wound tissue in matrix gel group was significantly higher than that in PBS group (with t values of 4.33 and 10.10, respectively, P<0.05). Compared with the previous time point within the group, the MVC of wound at each time point after injury in the two groups was increased significantly (P<0.05), except for PID 21 in PBS group (P>0.05). In PWHM 1, 2, 3, and 4, the expressions of TGF-β1 and α-SMA in scar tissue in matrix gel group were significantly lower than those in PBS group (with t values of -2.83, -5.46, -5.61, -8.63, -10.11, -5.79, -8.08, and -11.96, respectively, P<0.05). Compared with the previous time point within the group, the expressions of TGF-β1 and α-SMA in scar tissue in the two groups were increased significantly at each time point after wound healing (P<0.05), except for the α-SMA expression in matrix gel group in PWHM 4 (P>0.05). There was a significantly positive correlation between the expression of α-SMA and that of TGF-β1 in scar tissue in matrix gel group (r=0.92, P<0.05). On PID 14 and 21, the expressions of VEGF (with t values of 6.14 and 6.75, respectively, P<0.05) and EGF (with t values of 8.17 and 5.85, respectively, P<0.05) in wound tissue in matrix gel group were significantly higher than those in PBS group. Compared with the previous time point within the group, the expression of VEGF of wound at each time point after injury in the two groups was increased significantly (P<0.05), and the expression of EGF was decreased significantly (P<0.05).  Conclusions  Adipose stem cell matrix gel may significantly promote the wound healing of full-thickness skin defects in rabbit ears by promoting collagen deposition and expressions of VEGF and EGF in wound tissue, and may further inhibit the scar hyperplasia after wound healing by inhibiting collagen deposition and expressions of TGF-β1 and α-SMA in scar tissue.

     

    • FullText(HTML)
  • loading
    • References(31)
  • [1]
    NussbaumSR,CarterMJ,FifeCE,et al.An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds[J].Value Health,2018,21(1):27-32.DOI: 10.1016/j.jval.2017.07.007.
    [2]
    WangA,LvG,ChengX,et al.Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition)[J/OL].Burns Trauma,2020,8:tkaa017[2022-10-20].https://pubmed.ncbi.nlm.nih.gov/32685563/.DOI: 10.1093/burnst/tkaa017.
    [3]
    史亮亮,刘名倬,江政英,等.药物干预增生性瘢痕的研究进展[J].中华烧伤与创面修复杂志,2022,38(12):1179-1184.DOI: 10.3760/cma.j.cn501120-20211118-00388.
    [4]
    ShirakamiE,YamakawaS,HayashidaK.Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence[J/OL].Burns Trauma,2020,8:tkz003[2022-10-20].https://pubmed.ncbi.nlm.nih.gov/32341924/.DOI: 10.1093/burnst/tkz003.
    [5]
    史春梦.加强难愈合创面间充质干细胞治疗的基础与转化研究[J].中华烧伤与创面修复杂志,2022,38(11):999-1003.DOI: 10.3760/cma.j.cn501225-20220913-00405.
    [6]
    曹涛,肖丹,计鹏,等.肝细胞生长因子修饰的人脂肪间充质干细胞外泌体对糖尿病小鼠全层皮肤缺损的作用[J].中华烧伤与创面修复杂志,2022,38(11):1004-1013.DOI: 10.3760/cma.j.cn501225-20220731-00330.
    [7]
    李梁,杨青文,王士强,等.脂肪干细胞在糖尿病慢性创面中的基础研究及应用[J].中国糖尿病杂志,2021,29(6):477-480.DOI: 10.3969/j.issn.1006-6187.2021.06.016.
    [8]
    熊婷,冯晓玲.纳米脂肪的基础及临床应用研究进展[J].中华整形外科杂志,2020,36(6):691-695.DOI: 10.3760/cma.j.cnZHZXWKZZ-2018-0724-00327.
    [9]
    CaiY,LiJ,JiaC,et al.Therapeutic applications of adipose cell-free derivatives: a review[J].Stem Cell Res Ther,2020,11(1):312.DOI: 10.1186/s13287-020-01831-3.
    [10]
    王婧脂肪干细胞胶促进增生性瘢痕重塑的实验研究广州南方医科大学2019

    王婧.脂肪干细胞胶促进增生性瘢痕重塑的实验研究[D].广州:南方医科大学,2019.
    [11]
    郜敏,张杰,王际壮,等.低氧预处理大鼠脂肪源性间充质干细胞条件培养基对大鼠全层皮肤缺损创面愈合的影响[J].中华烧伤杂志,2020,36(9):803-812.DOI: 10.3760/cma.j.cn501120-20200508-00258.
    [12]
    WangJ,LiaoY,XiaJ,et al.Mechanical micronization of lipoaspirates for the treatment of hypertrophic scars[J].Stem Cell Res Ther,2019,10(1):42.DOI: 10.1186/s13287-019-1140-1.
    [13]
    DengC,WangL,FengJ,et al.Treatment of human chronic wounds with autologous extracellular matrix/stromal vascular fraction gel: a STROBE-compliant study[J].Medicine (Baltimore),2018,97(32):e11667.DOI: 10.1097/MD.0000000000011667.
    [14]
    NagelschmidtM,BeckerD,BönninghoffN,et al.Effect of fibronectin therapy and fibronectin deficiency on wound healing: a study in rats[J].J Trauma,1987,27(11):1267-1271.DOI: 10.1097/00005373-198711000-00011.
    [15]
    SullivanT,SmithJ,KermodeJ,et al.Rating the burn scar[J].J Burn Care Rehabil,1990,11(3):256-260.DOI: 10.1097/00004630-199005000-00014.
    [16]
    NedelecB,ShankowskyHA,TredgetEE.Rating the resolving hypertrophic scar: comparison of the Vancouver Scar Scale and scar volume[J].J Burn Care Rehabil,2000,21(3):205-212.DOI: 10.1067/mbc.2000.104750.
    [17]
    曹胜军,王凌峰,巴特,等.异体小鼠脂肪源性间充质干细胞-微孔化羊脱细胞真皮基质对小鼠全层皮肤缺损创面愈合的影响及相关机制[J].中华烧伤杂志,2018,34(12):901-906.DOI: 10.3760/cma.j.issn.1009-2587.2018.12.015.
    [18]
    YuWY,SunW,YuDJ,et al.Adipose-derived stem cells improve neovascularization in ischemic flaps in diabetic mellitus through HIF-1α/VEGF pathway[J].Eur Rev Med Pharmacol Sci,2018,22(1):10-16.DOI: 10.26355/eurrev_201801_14094.
    [19]
    施彦,涂龙翔,邓琴,等.经外源性血管内皮生长因子处理的大鼠表皮干细胞对深Ⅱ度烧伤大鼠创面愈合的影响及机制[J].中华烧伤杂志,2020,36(3):195-203.DOI: 10.3760/cma.j.cn501120-20191125-00441.
    [20]
    张锐,刘兰,谢德富,等.直流电场刺激脂肪来源干细胞修复糖尿病大鼠难愈性创面[J].中国组织工程研究,2023,27(10):1484-1491.
    [21]
    SorgH,TilkornDJ,MirastschijskiU,et al.Panta Rhei: neovascularization, angiogenesis and nutritive perfusion in wound healing[J].Eur Surg Res,2018,59(3/4):232-241.DOI: 10.1159/000492410.
    [22]
    ChingYH,SuttonTL,PierpontYN,et al.The use of growth factors and other humoral agents to accelerate and enhance burn wound healing[J].Eplasty,2011,11:e41.
    [23]
    赵朋,杨敏烈,储国平,等.猪膀胱脱细胞基质和猪脱细胞真皮基质对糖尿病小鼠全层皮肤缺损创面愈合的影响[J].中华烧伤杂志,2020,36(12):1130-1138.DOI: 10.3760/cma.j.cn501120-20200901-00399.
    [24]
    XuKP,LiY,LjubimovAV,et al.High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing[J].Diabetes,2009,58(5):1077-1085.DOI: 10.2337/db08-0997.
    [25]
    ZhangY,NiL,WangX,et al.Subcutaneous injection of epidermal growth factor for skin hydrofluoric acid burns[J].Int Wound J,2016,13(5):1023.DOI: 10.1111/iwj.12306.
    [26]
    姚永明,阎贺,张泽敏,等.兔脂肪源性间充质干细胞对兔皮肤深Ⅱ度烫伤创面愈合的影响[J].中华烧伤杂志,2016,32(7):402-407.DOI: 10.3760/cma.j.issn.1009-2587.2016.07.004.
    [27]
    邓呈亮,李修权,刘志远,等.自体脂肪源性基质血管成分局部移植对兔耳增生性瘢痕形成的影响及机制[J].中华烧伤杂志,2018,34(8):542-548.DOI: 10.3760/cma.j.issn.1009-2587.2018.08.012.
    [28]
    XieF,TengL,XuJ,et al.Adipose-derived mesenchymal stem cells inhibit cell proliferation and migration and suppress extracellular matrix synthesis in hypertrophic-scar and keloid fibroblasts[J].Exp Ther Med,2021,21(2):139.DOI: 10.3892/etm.2020.9571.
    [29]
    RozenfeldPA,de Los Angeles BollaM,QuietoP,et al.Pathogenesis of Fabry nephropathy: the pathways leading to fibrosis[J].Mol Genet Metab,2020,129(2):132-141.DOI: 10.1016/j.ymgme.2019.10.010.
    [30]
    ShindeAV,HumeresC,FrangogiannisNG.The role of α-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling[J].Biochim Biophys Acta Mol Basis Dis,2017,1863(1):298-309.DOI: 10.1016/j.bbadis.2016.11.006.
    [31]
    LiX,GuoL,YangX,et al.TGF-β1-induced connexin43 promotes scar formation via the Erk/MMP-1/collagen III pathway[J].J Oral Rehabil,2020,47 Suppl 1:S99-106.DOI: 10.1111/joor.12829.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(5)  / Tables(7)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (2513) PDF downloads(25) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return