Tissue Engineering and Regenerative Medicine

, Volume 16, Issue 6, pp 667–674 | Cite as

An Important Role of Macrophages for Wound Margin Regeneration in a Murine Flap Model

  • Ho-Ryun Won
  • Chorong Seo
  • Hye-Young Lee
  • Jin Roh
  • Chul-Ho Kim
  • Jeon Yeob JangEmail author
  • Yoo Seob ShinEmail author
Original Article



Macrophages have been known to have diverse roles either after tissue damage or during the wound healing process; however, their roles in flap wound healing are poorly understood. In this study, we aimed to evaluate how macrophages contribute to the flap wound regeneration.


A murine model of a pedicled flap was generated, and the time-course of the wound healing process was determined. Especially, the interface between the flap and the residual tissue was histopathologically evaluated. Using clodronate liposome, a macrophage-depleting agent, the functional role of macrophages in flap wound healing was investigated. Coculture of human keratinocyte cell line HaCaT and monocytic cell line THP-1 was performed to unveil relationship between the two cell types.


Macrophage depletion significantly impaired flap wound healing process showing increased necrotic area after clodronate liposome administration. Interestingly, microscopic evaluation revealed that epithelial remodeling between the flap tissue and residual normal tissue did not occurred under the lack of macrophage infiltration. Coculture and scratch wound healing assays indicated that macrophages significantly affected the migration of keratinocytes.


Macrophages play a critical role in the flap wound regeneration. Especially, epithelial remodeling at the flap margin is dependent on proper macrophage infiltration. These results implicate to support the cellular mechanisms of impaired flap wound healing.


Reconstruction Flap Wound healing Macrophage Inflammatory cell 



This study was supported by research Grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2018R1D1A1A02043691, NRF-2016R1D1A1B03932867).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Ajou University (IACUC approval No. 2017-0025).

Supplementary material

13770_2019_214_MOESM1_ESM.tif (10.3 mb)
Supplementary material 1 (TIFF 10542 kb)


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Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society 2019

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology - Head and Neck SurgeryChungnam National University HospitalDaejeonRepublic of Korea
  2. 2.Department of OtolaryngologyAjou University School of MedicineSuwonRepublic of Korea
  3. 3.Department of PathologyAjou University School of MedicineSuwonRepublic of Korea
  4. 4.Department of Molecular Science and TechnologyAjou UniversitySuwonRepublic of Korea

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