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KGF-2 and FGF-21 poloxamer 407 hydrogel coordinates inflammation and proliferation homeostasis to enhance wound repair of scalded skin in diabetic rats
  1. Xuanxin Yang1,2,
  2. Rongshuai Yang2,
  3. Min Chen2,
  4. Qingde Zhou2,
  5. Yingying Zheng2,
  6. Chao Lu2,
  7. Jianing Bi2,
  8. Wenzhe Sun2,
  9. Tongzhou Huang2,
  10. Lijia Li2,
  11. Jianxiang Gong2,
  12. Xiaokun Li1,2,
  13. Qi Hui2,
  14. Xiaojie Wang1,2
  1. 1Department of Dermatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
  2. 2School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
  1. Correspondence to Professor Xiaojie Wang; 18858811123{at}126.com; Dr Qi Hui; huiqi1976{at}163.com; Dr Xiaokun Li; profxiaokunli{at}163.com

Abstract

Objective The present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats.

Research design and methods In this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0.

Results A 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31.

Conclusions A KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.

  • type 2 diabetes
  • wound healing
  • combination therapy
  • growth factor(s)
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Footnotes

  • Contributors XW, XL, and XY conceived and designed the experiments. XY, QZ, RY, YZ, MC, and CL performed the experiments. QH analyzed and constructed the data figures. JB, WS, and TH contributed to reagents/analysis tools. LL and JG contributed materials. XW and XY wrote the manuscript. XW is the guarantor of this work and, as such, had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding This work was supported by a grant from the Ministry of Science and Technology of China (No. 2016ZX09101117), the National Natural Science Foundation of China (No. 81601695), and the Natural Science Foundation of the Zhejiang Province (No. LY17H150002 and No. LY17H300003).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All animal experiments were handled in accordance with the IACUC guidelines of Wenzhou Medical University (Zhejiang, China), which comply with NIH guidelines for the care and use of laboratory animals. All animal experiments were approved by the Animal Institutional Ethics Committee of Wenzhou Medical University (No. wydw2017-0102, Wenzhou, Zhejiang, China) and were performed following the guidelines for animal experimentation at Wenzhou Medical University. Humane treatment of all research animals was assured. This article does not contain any studies with human participants. All authors confirm that ethical principles were followed in the experiments of the present study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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