Mechanical Stretching Can Modify the Papillary Dermis Pattern and Papillary Fibroblast Characteristics during Skin Regeneration

Clinical application of mechanical stretching is a reconstructive method for skin repair. Although studies have reported dermal fibroblast heterogeneity, whether stretching affects individual fibroblast subpopulations equally remains unclear. In this study, we show the changes in dermal structure and papillary fibroblast (Fp) in regenerated human skin. Exhausted skin regeneration caused dermal-epidermal junction flattening, papillary dermis thinning, and an increase in type III collagen-to-type I collagen ratio, with upregulated hallmarks of aging. Well-regenerated skin displayed a notable increase in the Fp population. Consistent changes were observed in the rat expansion model. Moreover, we found that TGF beta 1 expression was especially increased in skin showing good regeneration. Activation of the TGF beta 1/SMAD2/3 pathway improved exhausted skin regeneration and resulted in increased collagen content and Fp proliferation, whereas pharmacological inhibition of TGF beta 1 action impacted well-regenerated skin. Short-term mechanical stretching that promoted skin regeneration enhanced Fp proliferation, extracellular matrix synthesis, and increased TGF beta 1 expression, leading to good regeneration. Conversely, long-term stretching induced premature Fp senescence, leading to poor regeneration. This work shows the mechanism of mechanical stretching in well-skin regeneration that enhances Fp proliferation and extracellular matrix synthesis through the TGF beta 1/SMAD2/3 pathway and highlights a crucial role of Fps in stretching-induced skin regeneration.

Automated summary

This study demonstrates the effects of mechanical stretching on skin regeneration in humans, showing that it increases the population of papillary fibroblasts (Fp) and collagen synthesis, improves skin regeneration through the TGF beta 1/SMAD2/3 pathway, but long-term stretching can lead to premature Fp senescence and poor regeneration.