![]() The skin is formed by three main layers (the epidermis, the dermis, and the hypodermis) with its appendages (hair, sweat and sebaceous glands, sensory neurons, blood and lymph vessels, etc.). ![]() It is constantly involved in numerous processes: water balance and temperature regulation, signal perception, hormone, neuropeptide and cytokine production and activation, etc. The skin plays an important role which cannot be overestimated its functioning ensures homeostasis and protects us from aggressive and causative agents in the environment. In this study, we focus on discussing the essentials, achievements, and challenges of cell-based therapy for skin tissue regeneration in the treatment of burn injury. Skin substitutes have shown high efficacy and cost-effectiveness compared to autologous skin replacement. The cumulative effect of cell-sheets, scaffolds, cell-scaffolds, and hydrogels with healing promoting factors triggers, accelerates, and enhances wound healing and re-epithelialization that leads to a reduction in scar formation and prevention of burn injury complication. Skin substitutes, especially cell-based ones, play critical role in overcoming this scarcity. Despite wide use, autologous skin grafts are deficient in the treatment of severe burns for patients with limited donor site area. The survival rates of patients with burns have significantly improved due to the application of various skin grafts over the last decades. Therefore, it is critical to promptly cover a burn injury using an appropriate approach to prevent them and save patients’ lives, besides providing intravenously fluids and nutrients to offset dehydration and replace lost proteins. Each of these complications can be fatal or make a patient suffer. The burned skin is extremely susceptible to bacteria and other pathogens, due to the loss of protection by intact layers of the skin. Another serious threat to lives of burn patients is an infection. The skin damage causes the death of skin cells, leading to an enormous loss of body fluids that is followed by dehydration, electrolyte imbalance, and renal and circulatory failure. Serious complications of deep or widespread burns can happen, e.g., sepsis due to bacterial infection, shock caused by hypovolemia, or scaring tissue contraction after improper wound healing. A burn ensues after the skin is damaged by heat, radiation, electricity, or chemicals. Burns remain as one of the most common injuries worldwide, with more than one million patients annually in the USA alone.
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