Tissue-engineered skin substitutes represent an innovative therapeutic option for the treatment of burns and skin ulcers as well as a powerful tool for fundamental research. To be efficient, in vitro skin substitutes must closely mimic human skin structures and exogenous material has to be reduced as much as possible. The self-assembly approach is based on the capacity of fibroblasts to create their own extracellular matrix in vitro, which allows the production of cell sheets that are easy to handle. Therefore, a skin substitute devoid of exogenous extracellular matrix proteins and synthetic material is produced, which demonstrates many histological, physico-chemical and mechanical characteristics found in normal human skin in vivo. A particularity of this approach is the possibility to add various other cell types (keratinocytes, melanocytes, adipocytes, endothelial and immunological cells, etc.) according to needs. Furthermore, pathological cells (hypertrophic scar, sclerodermic, tumoral and psoriatic cells) can be used for the production of pathological skin substitutes. The development of these models represents a key component in the fight against such diseases because they can lead to a better understanding of the pathology and to the development of new pharmaceutical therapies.This review will present the need for tissue-engineered skin substitutes, the implication of tissue engineering in the cutaneous field (basic and applied research), the selfassembly approach and its characteristics as well as the actual state of research on healthy and pathological selfassembled skin models.
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