Preservation of Eschar Prevents Excessive Wound Healing by Reducing M2 Macrophages Polarization.

Abstract

Removal of the eschar has gradually become a consensus on treatments of deep dermal necrosis after skin trauma in recent years, whereas exaggerated scar contracture and tissue proliferation developed during healing have received little attention. Here, the authors investigated the effects of eschar on excessive wound healing of small dermal damage and focused on the role M2 macrophages played, hoping to offer a theoretical basis to improve patients' cosmetic satisfaction. A mouse dorsal wound model (n = 12) was established by electric heating pads heating for 20 seconds on each side of the spine, and the left side was the preserved group. Macrophage numbers, expression of wound-healing-associated proteins, and inflammatory cytokine levels were assessed at different time points by immunohistochemistry and quantitative real-time polymerase chain reaction. A co-culture system of M2 macrophages and myofibroblasts was created in vitro. Immunohistochemistry, real-time polymerase chain reaction, and Western blot were performed to evaluate the proliferation, migration, and protein expression of myofibroblasts. Preserving eschar inhibited contraction-associated proteins (α-smooth muscle actin and vimentin) and collagen expression, inflammatory cytokine (IL-1β, IL-10, TFN-α, and IL-4) expression, and M2 macrophage infiltration. Mechanistically, M2 macrophages potentially contributed to excessive wound healing by promoting myofibroblasts proliferation, migration, and production of contraction-associated proteins. Eschar preservation in wounds could reduce inflammation and negatively modulate myofibroblasts by inhibiting M2 macrophage polarization and infiltration, preventing excessive wound contraction and collagen deposition.