An Overview on the Manufacturing of Functional and Mature Cellular Skin Substitutes

There are different types of skin diseases due to chronic injuries that impede the natural healing process of the skin. Tissue engineering has focused on the development of bioengineered skin or skin substitutes that cover the wound, providing the necessary care to restore the functionality of injured skin. There are two types of substitutes: acellular skin substitutes, which offer a low response to the body, and cellular skin substitutes (CSSs), which incorporate living cells and appear as a great alternative in the treatment of skin injuries due to their greater interaction and integration with the rest of the body. For the development of a CSS, it is necessary to select the most suitable biomaterials, cell components, and methodology of biofabrication for the wound to be treated. Moreover, these CSSs are immature substitutes that must undergo a maturing process in specific bioreactors, guaranteeing their functionality. The bioreactor simulates the natural state of maturation of the skin by controlling parameters such as temperature, pressure, or humidity, allowing a homogeneous maturation of the CSSs in an aseptic environment. The use of bioreactors not only contributes to the maturation of the CSSs but also offers a new way of obtaining large sections of skin substitutes or natural skin from small portions acquired from the patient, donor, or substitute. Based on the innovation of this technology and the need to develop efficient CSSs, this work offers an update on bioreactor technology in the field of skin regeneration.