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Autologous three-cellular cultured skin substitutes (CSS) are a tissue-engineered regenerative medicine product designed for the permanent closure of extensive full-thickness skin wounds. This complex skin substitute is composed of three primary autologous cell types: keratinocytes, melanocytes, and fibroblasts, which are derived from a patient's own skin biopsy. The cells are organized onto a scaffold of esterified hyaluronic acid, where fibroblasts form a dermal-like basement and keratinocytes and melanocytes (in a 1:20 ratio) form a pluristratified epithelial surface. Following surgical application, the hyaluronic acid scaffold is gradually resorbed and replaced by the host's connective tissue, while the transplanted cells integrate to restore both the structural integrity and pigmentation of the skin. This therapy has been investigated as a surgical alternative for treating severe burns, chronic ulcers, and giant congenital nevi.
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