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Tissue expansion has been widely used for plastic, reconstructive, and esthetic surgeries. A mouse scalp expansion model can effectively mimic the characteristics of human skin expansion. However, a detailed study of the histological features and ultrastructural characteristics of expanded scalp is lacking, especially early ultrastructural changes. Here, a mouse scalp expansion model was established and the expanded scalp samples were obtained on day 2 (group I) and 4 (group II) post final injection. Histological analysis revealed epidermal thickening, dermal thinning, subcutaneous fat thinning, and capsule formation in the expanded samples. Ultrastructural evaluation showed the presence of keratinocytes with numerous tonofibrils and damaged mitochondria, and several ruptured collagen fibers and increased number of active fibroblasts and myofibroblasts were observed in the dermis and capsules. Adipocyte dedifferentiation was detected in the expanded samples of both groups, but formation of autophagosomes was only detected in the dermal fibroblasts of group I. Thus, early changes in expanded tissue should be carefully monitored, as it may help avoid dermal thinning and promote expanded tissue regeneration. [ABSTRACT FROM AUTHOR]