Tissue Eng Regen Med.  2019 Dec;16(6):667-674. 10.1007/s13770-019-00214-x.

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

Affiliations
  • 1Department of Otorhinolaryngology - Head and Neck Surgery, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea.
  • 2Department of Otolaryngology, Ajou University School of Medicine, 164 Worldcup Street, Yeongtong-gu, Suwon 16499, Republic of Korea. manup1377@gmail.com, ysshinmd@ajou.ac.kr
  • 3Department of Pathology, Ajou University School of Medicine, 164 Worldcup Street, Yeongtong-gu, Suwon 16499, Republic of Korea.
  • 4Department of Molecular Science and Technology, Ajou University, 164 Worldcup Street, Yeongtong-gu, Suwon 16499, Republic of Korea.

Abstract

BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.

Keyword

Reconstruction; Flap; Wound healing; Macrophage; Inflammatory cell

MeSH Terms

Cell Line
Clodronic Acid
Coculture Techniques
Humans
Keratinocytes
Liposomes
Macrophages*
Regeneration*
Surgical Flaps
Wound Healing
Wounds and Injuries*
Clodronic Acid
Liposomes
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