Ideal Living Skin Equivalents, From Old Technologies and Models to Advanced Ones: The Prospects for an Integrated Approach.

The development of technologies for the generation and transplantation of living skin equivalents (LSEs) is a significant area of translational medicine. Such functional equivalents can be used to model and study the morphogenesis of the skin and its derivatives, to test drugs, and to improve the healing of chronic wounds, burns, and other skin injuries. The evolution of LSEs over the past 50 years has demonstrated the leap in technology and quality and the shift from classical full-thickness LSEs to principled new models, including modification of classical models and skin organoids with skin derived from human-induced pluripotent stem cells (iPSCs) (hiPSCs). Modern methods and approaches make it possible to create LSEs that successfully mimic native skin, including derivatives such as hair follicles (HFs), sebaceous and sweat glands, blood vessels, melanocytes, and nerve cells. New technologies such as 3D and 4D bioprinting, microfluidic systems, and genetic modification enable achievement of new goals, cost reductions, and the scaled-up production of LSEs.