An Important Role of Macrophages for Wound Margin Regeneration in a Murine Flap Model
- 21 Downloads
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.
KeywordsReconstruction 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.
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).
- 15.Kawanishi N, Mizokami T, Niihara H, Yada K, Suzuki K. Macrophage depletion by clodronate liposome attenuates muscle injury and inflammation following exhaustive exercise. Biochem Biophys Rep. 2016;5:146–51.Google Scholar
- 21.Matsumoto NM, Aoki M, Nakao J, Peng WX, Takami Y, Umezawa H, et al. Experimental rat skin flap model that distinguishes between venous congestion and arterial ischemia: the reverse u-shaped bipedicled superficial inferior epigastric artery and venous system flap. Plast Reconstr Surg. 2017;139:79e–84.CrossRefGoogle Scholar