Introduction: It is widely known that during development extracellular matrix components change to promote stiffness and increased density in adult skin. The purpose of this study was to determine whether these alterations in the mechanical properties of skin may underlie the different scar patterns observed in fetal (scarless) and adult (scarring) skin.

Methods: Baseline levels of intrinsic mechanical stress were established for fetal and adult murine skin and adult human skin using a small-scale tensiometer. Next, mechanical stress was artificially increased in murine skin and wounds to levels present in adult human skin. Tension was held at higher levels through the first two weeks of healing. Harvested wounds were analyzed by real-time RT-PCR, microarray and immunohistochemistry to determine changes in the matrix components collagen 1, collagen 3, and elastin and the matrix remodeling agents lysyl oxidase and MMP-9. To correlate in vivo findings with individual cell function, murine fibroblasts were cultured under mechanical strain and analyzed for expression profiles of those matrix and matrix remodeling components described above.

Results: Intrinsic mechanical stress, as defined by Young's Modulus, was greatest in adult human skin and lowest in fetal murine skin. In skin and wounds with increased tension, we observed significantly higher levels of collagen 1, collagen 3, and elastin. Matrix remodeling agents lysyl oxidase and MMP-9 were also increased. In vitro, fibroblasts cultured under high levels of mechanical stress exhibited increases in matrix components similar to those seen in vivo.

Conclusion: We propose that the higher tissue stiffness in adult skin activates different patterns of gene expression which alter matrix composition to promote scar formation in adult human wounds. It is conceivable that the scarless phenotype seen in fetal healing may be attributable to the different mechanical properties in fetal skin, specifically the lower levels of resting tensile stress. By manipulating the levels of mechanical stress in healing wounds, we can dramatically alter subsequent scar formation.