Enhancement of Wound Healing Efficacy by Increasing the Stability and Skin-Penetrating Property of bFGF Using 30Kc19α-Based Fusion Protein

Haein Lee, Young Hyeon An, Tae Keun Kim, Jina Ryu, G. Kate Park, Mihn Jeong Park, Junghyeon Ko, Hyunbum Kim, Hak Soo Choi, Nathaniel S. Hwang, Tai Hyun Park

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The instability of recombinant basic fibroblast growth factor (bFGF) is a major disadvantage for its therapeutic use and means frequent applications to cells or tissues are required for sustained effects. Originating from silkworm hemolymph, 30Kc19α is a cell-penetrating protein that also has protein stabilization properties. Herein, it is investigated whether fusing 30Kc19α to bFGF can enhance the stability and skin penetration properties of bFGF, which may consequently increase its therapeutic efficacy. The fusion of 30Kc19α to bFGF protein increases protein stability, as confirmed by ELISA. 30Kc19α-bFGF also retains the biological activity of bFGF as it facilitates the migration and proliferation of fibroblasts and angiogenesis of endothelial cells. It is discovered that 30Kc19α can improve the transdermal delivery of a small molecular fluorophore through the skin of hairless mice. Importantly, it increases the accumulation of bFGF and further facilitates its translocation into the skin through follicular routes. Finally, when applied to a skin wound model in vivo, 30Kc19α-bFGF penetrates the dermis layer effectively, which promotes cell proliferation, tissue granulation, angiogenesis, and tissue remodeling. Consequently, the findings suggest that 30Kc19α improves the therapeutic functionalities of bFGF, and would be useful as a protein stabilizer and/or a delivery vehicle in therapeutic applications.

Original languageEnglish
Article number2000176
JournalAdvanced Biology
Volume5
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Funding Information:
H.L. and Y.‐H.A. contributed equally to this work. This work was financially supported by the Ministry of Science and ICT by the Korean Government (NRF‐2017M3A9C6031786). In addition, this work was partly supported by US NIH grant NIBIB (#R01EB022230).

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Keywords

  • basic fibroblast growth factor
  • cell-penetrating proteins
  • protein stabilizer
  • skin wound healing
  • transdermal delivery

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