Abstract
BackgroundTissue expansion is a procedure that promotes skin regeneration by mechanical stretch. During the stress and relaxation cycle, the skin undergoes a repeated microtrauma which triggers an immune response leading to the recruitment of macrophages to repair the damaged tissue. Macrophages have been found to be necessary for tissue repair and wound healing, but their effects on skin regeneration during mechanical stretch remain unclear.MethodsThe dynamic changes of macrophages in the rat skin tissues undergoing expansion were quantitatively determined by immunohistochemistry staining. The area of the expanded skin, skin thickness, dermal collagen density, cell proliferation and tissue vascularization were examined to determine the effects of macrophages on the expanding skin. The phenotypes of macrophages and the growth factors related to skin regeneration were also examined to evaluate the underlying mechanisms for the involvement of macrophages in skin regeneration. As a comparison, the tissue samples of expanding skin in which the macrophages were depleted by topically utilizing clodronate liposomes were also evaluated.ResultsThe number of skin macrophages in skin maintained in the high level during the skin expansion compared to non-expanded skin. We found that a switch from an M1- to M2-dominant response during tissue expansion. After the macrophages were depleted, the skin regeneration was inhibited, as evidenced by a smaller expansion area, thinner skin layers and decreased cell proliferation rate, collagen synthesis and, skin vascularization. The secretion of epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) were decreased when macrophages were depleted.ConclusionsOur findings suggest that macrophages are necessary for skin regeneration during tissue expansion. Modulating inflammation may provide a key therapeutic strategy to promote skin growth under mechanical strain.
Highlights
Tissue expansion is a procedure that promotes skin regeneration by mechanical stretch
Our results clearly demonstrated that macrophage depletion inhibits skin regeneration during tissue expansion determined by quantitation of skin area, skin thickness, collagen synthesis, cell proliferation, and vascularization
Dynamic changes of tissue macrophage density during the tissue expansion To evaluate the differences between the expanded and non-expanded skin macrophage response, we sought to count the number of macrophages in the skin using immunostaining
Summary
Tissue expansion is a procedure that promotes skin regeneration by mechanical stretch. Macrophages have been found to be necessary for tissue repair and wound healing, but their effects on skin regeneration during mechanical stretch remain unclear. Tissue expansion is a procedure to harvest large skin tissue in response to mechanical force by implanting a silicone expander subcutaneously and continuous injecting saline into it. This process, first described by Neumann [1] and later improved by Radovan [2] and Austad et al [3], is one of the most important surgical techniques in plastic and reconstructive surgery. The mechanism by which skin responds to mechanical strain remains to be elucidated
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