An injectable thermosensitive hydrogel for sustained release of apelin-13 to enhance flap survival in rat random skin flap

  • Wenhao Zheng
  • Jinwu Wang
  • Linzhen Xie
  • Huanguang Xie
  • Chunhui Chen
  • Chuanxu Zhang
  • Dingsheng Lin
  • Leyi CaiEmail author
Delivery Systems Original Research
Part of the following topical collections:
  1. Delivery Systems


With the advantage of handy process, random pattern skin flaps are generally applied in limb reconstruction and wound repair. Apelin-13 is a discovered endogenous peptide, that has been shown to have potent multiple biological functions. Recently, thermosensitive gel-forming systems have gained increasing attention as wound dressings due to their advantages. In the present study, an apelin-13-loaded chitosan (CH)/β-sodium glycerophosphate (β-GP) hydrogel was developed for promoting random skin flap survival. Random skin flaps were created in 60 rats after which the animals were categorized to a control hydrogel group and an apelin-13 hydrogel group. The water content of the flap as well as the survival area were then measured 7 days post-surgery. Hematoxylin and eosin staining was used to evaluate the flap angiogenesis. Cell differentiation 34 (CD34) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry and Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme linked immunosorbent assays (ELISAs). Oxidative stress was estimated via the activity of tissue malondialdehyde (MDA) and superoxide dismutase (SOD). Our results showed that CH/β-GP/apelin-13 hydrogel could not only reduce the tissue edema, but also improve the survival area of flap. CH/β-GP/apelin-13 hydrogel also upregulated levels of VEGF protein and increased mean vessel densities. Furthermore, CH/β-GP/apelin-13 hydrogel was shown to significantly inhibit the expression of TNF-α and IL-6, along with increasing the activity of SOD and suppressing the MDA content. Taken together, these results indicate that this CH/β-GP/apelin-13 hydrogel may be a potential therapeutic way for random pattern skin flap.



This study was supported by the Zhejiang Medical and Health Science and Technology Plan Project (No. 2017KY480) and National Natural Science Foundation of China (No. 81701928).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Wenhao Zheng
    • 1
  • Jinwu Wang
    • 1
  • Linzhen Xie
    • 1
  • Huanguang Xie
    • 1
  • Chunhui Chen
    • 1
  • Chuanxu Zhang
    • 1
  • Dingsheng Lin
    • 1
  • Leyi Cai
    • 1
    Email author
  1. 1.Department of Orthopaedic SurgeryThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouChina

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