Tissue-engineered skin substitutes and cultured human skin cells have been developed since 1975 for treating major skin loss due to chronic wounds. Tissue- engineered skin substitutes can be classified according to the presence (cellular) or absence (acellular) of living cells, the use of cells or tissue that is autologous (from the patient), allogeneic (from another human) or xenogeneic (from animal), either biological or synthetic biomaterials, and involve physical stimulation to create a living substitute. CTERM had started the translational and clinical study of tissue-engineered skin substitutes by culturing autologous skin cells with the patient’s autologous serum. The single and bilayered tissue engineered skin substitute was produced by polymerizing the skin cells in a patient’s autologous plasma to form a layer of hydrogel that later be implanted into the wound area. The use of skin substitutes is suitable for alleviating non-healing chronic wounds, as such wounds are deeper and involve a larger total body surface area, or for non-healing smaller wounds, due to the underlying factors such as diabetic, trauma or burn cases.