At least 265,000 deaths are attributed to burns and fires worldwide per year according to the World Health Organization [1]. Recently, drifting smoke from extreme wildfires in Canada darkened the skies of the US and Europe, and the Maui fires (Lahaina, Hawaii) killed 115 people and left hundreds missing. The number of deaths caused by fires this year may have dramatically increased. Africa, with a high proportion of low-income countries, has been reported to have the highest rates of burn infections and mortality, as well as a disproportionally high number of burn incidences among children, compared with Canada and the United States [1]. It is important to increase the understanding of the pathophysiology of burn wounds and develop more clinical approaches.

Both the etiology and the pathophysiology of burn injuries are complicated, and mitochondrial dysfunction is considered to play a key role in burn trauma [2,3]. After a burn, inflammatory factors, ischemia-reperfusion injury, and sublethal fever can cause mitochondrial dysfunction at the site of injury [4,5]. During the early stages of burn injury, the body consumes a large amount of energy and maintains a high catabolic state. However, in the injured state, the body's energy metabolism is often difficult to maintain, which hinders the repair of damaged tissues [6]. Traditional anti-inflammatory treatments and growth factor supplementation for burns cannot effectively treat mitochondrial dysfunction. Thus, supplementation of injured tissue with additional mitochondria may be beneficial.

Mitochondrial transplantation (MT) is a new treatment method for mitochondrial dysfunction based on mitochondrial transfer, and it aims to restore normal cell function by replacing or supporting damaged mitochondria. Mitochondrial transfer, whereby cells can export some mitochondria and pass them on to recipient cells, was discovered in the past two decades and has been shown to play an important role in regulating cell metabolism, cancer, the immune system, tissue homeostasis maintenance, mitochondrial quality control, wound healing, and adipose tissue function [7]. MT is a class of mitochondrial transfer whereby isolated mitochondria are injected either into damaged tissues or into the circulation in the animal model, or co-cultured with cells in the cell model [[8], [9], [10], [11]]. As a novel transplantation technique, MT differs from the transplantation of organs, tissues, and cells in the sense that it is based on subcellular transplantation of organelles (mitochondria). It has been reported that MT exhibits therapeutic effects in many animal models of specific tissue or organ injuries, including the heart, brain, liver, kidney, lung, skeletal muscle, and skin, and even in a variety of diseases such as inflammation and tumors [8,11,12]. Most astonishingly, two clinical investigations have been completed at Boston Children's Hospital in 2017 and 2021 [13,14] whereby mitochondria isolated from the autologous rectus abdominis muscle were injected into heart regions with aberrant cardiac activity. This greatly improved the heart function of pediatric patients, and extracorporeal membrane oxygenation was no longer required to keep them alive. Based on these findings, we hypothesize that MT may exhibit therapeutic effects against skin burns.

In our previous study, we found that MT successfully reversed the negative effects of UV radiation on HeLa cells, reduced mitochondrial malfunction, and restored regular cell activity [15]. We found that it is in fact not the mitochondrial components but the structurally intact mitochondria themselves that are responsible for the protective effect of MT on UV radiation-damaged cells. This study hence provided an experimental foundation for the use of MT in the treatment of skin burns. In the present study, a deep partial-thickness skin-burn mouse model was established using Kunming mice to evaluate the wound-healing function of MT, and a heat-injured cell model based on human immortalized epidermal cells (HaCaT) was used for verification and further intensive study.