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Volume 37 Issue 12
Dec.  2021
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2021  >  37(12): 1166-1174
Chen AX,Chen YB,Jiang YF,et al.Effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats[J].Chin J Burns,2021,37(12):1166-1174.DOI: 10.3760/cma.j.cn501120-20200927-00424.
Citation: Chen AX,Chen YB,Jiang YF,et al.Effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats[J].Chin J Burns,2021,37(12):1166-1174.DOI: 10.3760/cma.j.cn501120-20200927-00424.
shu

Effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats

doi: 10.3760/cma.j.cn501120-20200927-00424
  • 1.

    Department of Plastic and Reconstructive Surgery, the First Medical Center of PLA General Hospital, Beijing 100853, China

  • 2.

    Department of Wound Repair Surgery, Special Medical Center of Strategic Support Force, Beijing 100101, China

Funds:

Support Fund of General Hospital of PLA ZH19011

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  • Corresponding author: Han Yan, Email: 13720086335@163.com
  • Received Date: 2020-09-27
    Abstract
  •       Objective     To investigate the effects of temperature-sensitive hydroxybutyl chitosan hydrogel on wound healing of full-thickness skin defect in rats.      Methods     The experimental research method was used. Fifty-one no matter male or female Sprague-Dawley rats aged 7-10 weeks were selected, and two round full-thickness skin defect wounds with a diameter of 2 cm were created on the back of each rat at a distance about 1.0 cm to the spine. The rats were divided into temperature-sensitive hydrogel group, gel group, and blank control group according to the random number table, with 17 rats and 34 wounds in each group. Wounds of rats in the first two groups were applied respectively with 0.3 mL temperature-sensitive hydroxybutyl chitosan hydrogel and carboxymethyl chitosan hydrogel immediately after injury, and the wounds of rats in blank control group received no treatment. The wounds of rats in the three groups were all covered with vaseline oil gauze. The states of temperature-sensitive hydroxybutyl chitosan hydrogel in wounds of rats in temperature-sensitive hydrogel group and carboxymethyl chitosan hydrogel in wounds of rats in gel group were observed every day when the dressings were changed, and the difficulty of vaseline oil gauze removal was recorded. On the 3rd, 7th, 10th, 14th, and 21st day after injury, the wound healing of rats in the three groups was observed and the wound healing rates were calculated. On the 3rd, 7th, 10th, 14th, and 21st day after injury, tissue from 4 wounds of 2 rats in each group was collected for the following observation and detection. The infiltration of inflammatory cells, angiogenesis, and re-epithelialization were observed by hematoxylin eosin staining. The regeneration and remodeling of collagen fibers were observed by Masson staining, and the collagen volume fraction was calculated. The expressions of interleukin-6 (IL-6), transforming growth factor β1 (TGF-β1), and matrix metalloproteinase-1 (MMP-1) were detected by enzyme-linked immunosorbent assay method. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni test.      Results     The carboxymethyl chitosan gel in wounds of rats in gel group was liquid gel and could flow with the body position, while the temperature-sensitive hydroxybutyl chitosan hydrogel in wounds of rats in temperature-sensitive hydrogel group was solid gel and could not flow with the body position, and the distribution of the latter was more uniform. The vaseline oil gauzes were easily removed in wounds of rats in temperature-sensitive hydrogel group, while the vaseline oil gauzes were difficult to remove in the other two groups. On the 3rd, 7th, 10th, 14th, and 21st day after injury, the wound granulation tissue of rats grew well in temperature-sensitive hydrogel group and gel group, with no obvious infection, and two rats in blank control group died of wound infection on the 3rd and 5th day after injury. On the 7th, 10th, 14th, and 21st day after injury, the wound healing rates of rats in temperature-sensitive hydrogel group and gel group were significantly higher than that in blank control group (P<0.01). On the 10th day after injury, the wound healing rate of rats in temperature-sensitive hydrogel group was significantly higher than that in gel group (P<0.05). A large number of neutrophils and lymphocytes infiltrated into the wounds of rats in the three groups on the 3rd day after injury. The infiltration of inflammatory cells  was gradually reduced and the wound healed gradually in rats of temperature-sensitive hydrogel group and gel group from the 7th to 21st day after injury, and the epidermis and dermis could be seen, without hair follicles and other skin appendages. The wounds of rats in blank control group did not heal completely on 21st day after injury. From the 3rd to 10th day after injury, the newly formed collagen fibers increased gradually in the wounds of rats in the three groups. On the 14th and 21st day after injury, the collagen fibers in the wounds of rats in temperature-sensitive hydrogel group and gel group were denser and more orderly than those in blank control group. On the 10th, 14th, and 21st day after injury, the collagen volume fraction of wounds of rats in temperature-sensitive hydrogel group and gel group was significantly higher than that in blank control group (P<0.01). On the 14th day after injury, the collagen volume fraction of wounds of rats in temperature-sensitive hydrogel group was significantly higher than that in gel group (P<0.01). On the 3rd, 7th, and 10th day after injury, the expressions of IL-6 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group (P<0.01), and the expressions of IL-6 in wounds of rats in gel group were significantly lower than those in blank control group (P<0.01). On the 3rd, 7th, and 10th day after injury, the expressions of TGF-β1 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group (P<0.01). The expressions of TGF-β1 in wounds of rats in gel group were significantly lower than those in blank control group on the 3rd and 7th day after injury (P<0.01), and the expression of TGF-β1 in wounds of rats in gel group was significantly higher than that in blank control group on the 10th day after injury (P<0.01). On the 14th day after injury, the expression of TGF-β1  in wounds of rats in gel group was significantly higher than that in temperature-sensitive hydrogel group and blank control group (P<0.01). On the 21st day after injury, the expression of TGF-β1 in wounds of rats in temperature-sensitive hydrogel group was significantly lower than that in gel group and blank control group (P<0.01), and the expression of TGF-β1 in wounds of rats in gel group was significantly lower than that in blank control group (P<0.01). On the 7th day after injury, the expression of MMP-1 in wounds of rats in gel group was significantly higher than that in temperature-sensitive hydrogel group and blank control group (P<0.01). On the 10th, 14th, and 21st day after injury, the expressions of MMP-1 in wounds of rats in temperature-sensitive hydrogel group were significantly higher than those in gel group and blank control group (P<0.01). On the 10th day after injury, the expression of MMP-1 in wounds of rats in gel group was significantly lower than that in blank control group (P<0.01). On the 14th and 21st day after injury, the expressions of MMP-1 in wounds of rats in gel group were significantly higher than those in blank control group (P<0.01).      Conclusions     Temperature-sensitive hydroxybutyl chitosan hydrogel can promote the healing of full-thickness skin defect wounds in rats by increasing the expressions of IL-6, TGF-β1, and MMP-1, regulating the wound healing environment, inhibiting inflammatory reaction, improving the strength of tissue repair, and promoting collagen synthesis or decomposition

     

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    • References(32)
  • [1]
    StrandSP,LeluS,ReitanNK,et al.Molecular design of chitosan gene delivery systems with an optimized balance between polyplex stability and polyplex unpacking[J].Biomaterials,2010,31(5):975-987.DOI: 10.1016/j.biomaterials.2009.09.102.
    [2]
    ChenMC,WongHS,LinKJ,et al.The characteristics, biodistribution and bioavailability of a chitosan-based nanoparticulate system for the oral delivery of heparin[J].Biomaterials,2009,30(34):6629-6637.DOI: 10.1016/j.biomaterials.2009.08.030.
    [3]
    TchemtchouaVT,AtanasovaG,AqilA,et al.Development of a procedure to simultaneously isolate RNA, DNA, and proteins for [corrected] characterizing cells invading or cultured on chitosan scaffolds[J].Anal Biochem,2009,393(1):145-147.DOI: 10.1016/j.ab.2009.06.013.
    [4]
    Van ToanN, NgCH, AyeKN,et al.Production of high-quality chitin and chitosan from preconditioned shrimpshells[J].J Chem Technol Biotech,2006,81(7):1113-1118. DOI: 10.1002/jctb.1437.
    [5]
    MoriT,MurakamiM,OkumuraM,et al.Mechanism of macrophage activation by chitin derivatives[J].J Vet Med Sci,2005,67(1):51-56.DOI: 10.1292/jvms.67.51.
    [6]
    尹刚,魏长征,郭兴锋,等.温敏性壳聚糖止血膜止血作用的实验研究[J].中国修复重建外科杂志,2013,27(5):624-627.DOI: 10.7507/1002-1892.20130137.
    [7]
    陈寅生,侯春林,魏长征,等.羟丁基壳聚糖的生物相容性研究[J].生物骨科材料与临床研究,2015,12(3):14-17,后插1.DOI: 10.3969/j.issn.1672-5972.2015.03.004.
    [8]
    毛珺,周应山,吴庭.高吸型壳聚糖敷料的创面止血及促愈合效果[J].中国组织工程研究,2016,20(16):2391-2396.DOI: 10.3969/j.issn.2095-4344.2016.16.015.
    [9]
    杨俊杰,刘志强,袁振良,等.温敏性壳聚糖水凝胶对脂肪来源干细胞生物学性能影响的实验研究[J].军医进修学院学报,2011,32(10):1059-1061,1072.DOI: 11-3275/R.20110701.0850.001.
    [10]
    余珍,章志量,尹洪萍,等.壳聚糖天然高分子衍生物促进大鼠皮肤愈合[J].生物医学工程学杂志,2014,31(1):142-145.DOI: 10.7507/1001-5515.20140028.
    [11]
    JiangY,WangJ,WangY,et al.Self-emulsifying drug delivery system improves preventive effect of curcuminoids on chronic heart failure in rats[J].Saudi Pharm J,2018,26(4):528-534.DOI: 10.1016/j.jsps.2018.02.003.
    [12]
    ZengM,ZhangN,HeY,et al.Histological validation of cardiac magnetic resonance T1 mapping for detecting diffuse myocardial fibrosis in diabetic rabbits[J].J Magn Reson Imaging,2016,44(5):1179-1185.DOI: 10.1002/jmri.25268.
    [13]
    SugawaraT,GallucciRM,SimeonovaPP,et al.Regulation and role of interleukin 6 in wounded human epithelial keratinocytes[J].Cytokine,2001,15(6):328-336.DOI: 10.1006/cyto.2001.0946.
    [14]
    DesmouliereA,GeinozA,GabbianiF,et al.Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and inquiescent and growing cultured fibroblasts [J]. J Cell Biol, 1993,122(1):103-111.
    [15]
    ZambrunoG, MarchisioPC, MarconiA, et al.Transforming growth factor-beta 1 modulates beta 1 and beta 5 integrin receptors and induces the de novo expression of the alpha v beta 6 heterodimer in normal humankeratinocytes:implications for wound healing [J].J Cell Biol, 1995,129(3):853-865. DOI: 10.1083/jcb.129.3.853.
    [16]
    FangX,HuX,ZhengZ,et al.Smad interacting protein 1 influences transforming growth factor-β1/Smad signaling in extracellular matrix protein production and hypertrophic scar formation[J].J Mol Histol,2019,50(6):503-514.DOI: 10.1007/s10735-019-09844-w.
    [17]
    吕大伦, 徐姝娟, 陈雷, 等. 人促红细胞生成素对大鼠急性创面转化生长因子β1/Smad3信号转导通路的影响 [J]. 中华烧伤杂志,2018,34 (10): 719-726. DOI: 10.3760/cma.j.issn.1009-2587.2018.10.013.
    [18]
    SerbanAI,StancaL,GeicuOI,et al.RAGE and TGF-β1 cross- talk regulate extracellular matrix turnover and cytokine synthesis in AGEs exposed fibroblast cells[J].PLoS One,2016,11(3):e0152376.DOI: 10.1371/journal.pone.0152376.
    [19]
    CastagninoP,LorenziMV,YehJ,et al.Neu differentiation factor/heregulin induction by hepatocyte and keratinocyte growth factors[J].Oncogene,2000,19(5):640-648.DOI: 10.1038/sj.onc.1203357.
    [20]
    YuanB,BroadbentJA,HuanJ,et al.The effects of adipose stem cell-conditioned media on fibrogenesis of dermal fibroblasts stimulated by transforming growth factor-β1[J].J Burn Care Res,2018,39(1):129-140.DOI: 10.1097/BCR.0000000000000558.
    [21]
    GültekinND,BenzerM,Tekin-NeijmannŞ.Is there any relation between connective tissue growth factor and scar tissue in vesicoureteral reflux?[J].Turk J Pediatr,2019,61(1):71-78.DOI: 10.24953/turkjped.2019.01.011.
    [22]
    刘霞,李凯琳,张梦莲.血清EPO、TGF-β1、细胞间黏附分子-1与Ⅱ度烧伤患者创面愈合及瘢痕程度的关系分析[J].中国美容医学,2020,29(6):101-105.
    [23]
    况芳,张志,陈宾,等.人增生性瘢痕成纤维细胞中SnoN的表达及其参与增生性瘢痕形成的机制[J].中华烧伤杂志,2017,33(10):634-638.DOI: 10.3760/cma.j.issn.1009-2587.2017.10.011.
    [24]
    刘昌玲,张志,刘志河,等.Smurf2对增生性瘢痕TGF-β1信号通路负向调节因子Smad7的影响及调控机制[J].中华整形外科杂志,2018,34(12):1059-1069.DOI: 10.3760/cma.j.issn.1009-4598.2018.12.016.
    [25]
    GillSE,ParksWC.Metalloproteinases and their inhibitors: regulators of wound healing[J].Int J Biochem Cell Biol,2008,40 (6/7):1334-1347.DOI: 10.1016/j.biocel.2007.10.024.
    [26]
    RobertsAB,SpornMB,AssoianRK,et al.Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro[J].Proc Natl Acad Sci U S A,1986,83(12):4167-4171.DOI: 10.1073/pnas.83.12.4167.
    [27]
    GallucciRM,SimeonovaPP,MathesonJM,et al.Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice[J].FASEB J,2000,14(15):2525-2531.DOI: 10.1096/fj.00-0073com.
    [28]
    MinagawatT, OkamuraY, ShigemasaY,et al.Effects of molecular weilght and deacetylation degree of chitin/chitosan on wound healing[J]. Carbohyd Polym,2007,67:640-644. DOI: 10.1016/j.carbpol.2006.07.007.
    [29]
    ChandraH,BishnoiP,YadavA,et al.Antimicrobial resistance and the alternative resources with special emphasis on plant-based antimicrobials-a review[J].Plants (Basel),2017,6(2):16. DOI: 10.3390/plants6020016.
    [30]
    FiliusPM,GyssensIC.Impact of increasing antimicrobial resistance on wound management[J].Am J Clin Dermatol,2002,3(1):1-7.DOI: 10.2165/00128071-200203010-00001.
    [31]
    MaloneM,BjarnsholtT,McBainAJ,et al.The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data[J].J Wound Care,2017,26(1):20-25.DOI: 10.12968/jowc.2017.26.1.20.
    [32]
    周思政.皮肤创伤愈合和增生性瘢痕动物模型的研究进展[J].组织工程与重建外科杂志,2018,14(1):48-52.DOI: 10.3969/j.issn.1673-0364.2018.01.013.
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