**1. Introduction**

The skin is the largest organ of the body, and its destruction, especially caused by burn injuries, is sufficient to be life threatening. Burns are responsible for many pathophysiological changes, resulting in a severe form of trauma that initiates several complications such as an escalation in infection and mortality rates as well as prolonged hospitalization and time of inactivity [1, 2]. For affected large surface area, burns may turn into a systemic problem affecting a various range of organs [3]. Consequently, there will be an intense inflammatory process and prolonged hypermetabolism, coordinated by hormones, cytokines, and acute phase proteins, which are associated with delayed wound healing process, enormous catabolism, multi-organ failure, and death [4]. Further, burn patients also will associate with anxiety, sleep disturbances, social avoidance, depression, and a disruption in activities of daily living after physical rehabilitation [5].

In decades, many important advances have been made for the improvements of the burn care; however, more still needs to be undertaken. The comprehensive study of burn pathophysiology is vital for further improvements of the current treatment strategies. Numerous experimental models have been established and can be applied to address the systemic, cellular, or molecular responses that occur in burn injuries, particularly the development of animal models. The use of these burn animal models is crucial for burn research especially for investigating the properties of new medicines, as it is known that novel treatment strategies should be initially tested at the experimental level before the clinical use [6]. For accurately investigating any therapeutic approaches and relevantly translating to the clinical,

the utilization of animal models has to be reproducible and as close as possible to burn lesions occurring in humans. Nevertheless, each animal model has advantages and limitations that determine its translational significance for burn treatments. In addition, the selection of the model should consider the anatomical and physiological characteristics of interspecies that reflect the differences in how different types of wounds heal and analytical techniques be applied. This chapter will further discuss the common animal models of burn injury as well as provide researchers with a better understanding of their benefits and limitations for the burn treatment design that is proposed to be clinically applicable to humans.

## **2. Burn wound management**

Burn injuries differ in their cause types and severity; hence, its treatment can be challenging to be managed. The first and second degrees of burn injuries usually are treated with the moisturizer, the topical agents, and/or an antimicrobial creams advised by the doctor [7]. This condition will typically heal within 2 weeks. On the other hand, because third degree of burn injuries destroys all of the skin layers, the majority of wound will tend to severely long-term consequences and cannot be managed by the primary healing process, so the additional surgical procedures, including skin grafting, skin substitutes, and the application of advanced wound dressing, are required [8, 9]. They act as filler to increase the dermal component of wound, improve the re-epithelization, and reduce the inhibitory factors and the inflammatory responses of wound healing, and therefore subsequent scarring [9, 10]. Numerous options for skin substitutes, dermal analogs, and advanced dressings existed, which can be broadly divided and utilized depending on the severity of burn injuries [11]. However, removing the eschar and covering the wound as early as possible are crucial since the main challenge in treating third degree of burn injuries is avoiding infection from any contaminations. In addition, appropriate deep burn care providing protection from physical damage and supporting the circulation of gas and moisture as well as a comfort to enhance the functional recovery should also be the priorities in severe burn wound care.

Advanced burn care has been associated with a deeper insight of the pathophysiology of burn wound healing as it demands the collaboration of many different tissues and cells that contribute to each phase of wound healing [12]. In severe burn, the phases of wound healing including inflammation, proliferation, matrix synthesis, and contraction, are dynamic and complex and tend to overlap [13]. Therefore, a better understanding of these phases is a key concept to continuously develop an advanced severe burn wound management.

Experimental model is essential when studying on the burns and its underlying mechanisms. Many animal models of burn injuries using mice, rats, rabbits, dogs, and pigs are reported. They have been widely used to examine the burn wound pathology, the effect of systemic drug application, local therapy, and the effect of burn trauma on the entire organism [14–16]. The use of animal models is considered suitable as valuable tools to examine the burn pathophysiology instead of *in vitro* experiment due to the heterogeneous nature of the burns and its similarity to the characteristics of the human skin. The accurate animal model that closely mimics the overlapping phases of severe burn wound would enable the researchers to investigate the potential of novel treatments and study each phase more precisely. However, each animal model of burn has its own advantages and limitations, so the evaluation of several models of burn wound in animals is important and will be further described below.

**45**

animals are necessary.

**3.1 Mouse**

system [30, 31].

*Animal Models of Burn Wound Management DOI: http://dx.doi.org/10.5772/intechopen.89188*

**3. Animal models in burn wound studies**

The use of animals as experimental models in various biological researches for transposition into human physiology was initially provoked by Bernard in 1865 [17]. Over time, the notable similarities of anatomy and physiology between humans and animals have further encouraged many researchers to investigate a large range of mechanisms and therapies in the animal models before translating their findings to humans. In burn studies, there are some common techniques for producing wound burns in the animal model including hot water, hot metal tools, electricity, and heated paraffin [18–20]. In these methods, the back of the animal is shaved, and a heated material is executed to the skin to induce the desired burn surface area. The specific parameters such as raised temperatures and duration of exposure are required in each different burn models [21–23]. Furthermore, the integral planning for the burn animal model experiment is also crucial to be estimated. The most significant difference in the skin histology between human and animal is the density of hair. The rapidity of reepithelialization and the morphology of hair follicle are extremely influenced by the hair cycle; it would affect the planimetry area of wound and the microscope data of observable skin biopsy [24–26]. For instance, the hair cycle of rodents is short (approximately around 23–28 days). In order to avoid their hair cycle effects for the evaluation of the wound, rodents with a similar birth date should be used. Because different animals possess different hair cycles, the specific time consideration of each animal model is necessary to be highlighted. In addition, the hair might reduce the heat transfer, and some serious infections source could be hiding in the hair; thus the animal hair needs to be thoroughly depilated. Shaving by hair clipper and then applying with hair removal cream can remove the hair entirely. However, the hair removal cream might induce contact dermatitis so its administration time should be carefully controlled. Last but not least, appropriate post-operation care is needed to be considered too in order to elevate the survival rate of animal. The rational use of antibiotics can prevent wound infections, and the proper administration of analgesics can improve the appetite and self-harm of the animal [27, 28]. Moreover, large areas of burns can also cause severe loss of body fluids; therefore, intensive monitoring and handling for the dehydration of

The right choice of method of burn induction and its maintenance in animal models are important as this impacts the burn outcome and determines how the wounds are treated. There is diversity among the species in the structure and anatomy of the skin along with their pros and cons as an experimental burn injury model. In this section, several animal models of burn in literature will be evaluated.

As a research model, mouse contains the major layers of the human skin (e.g.,

In burn, mouse animal models are usually used to understand the burn wound healing process and have a reproducible model. Recently, Lateef et al. demonstrated a highly reproducible partial-thickness injury in mouse that mimics the key aspects

epidermis, dermis) and provides the main insights of the signaling pathways associated in the healing process due to the variety of mouse-specific reagents and transgenic feasibility in mouse. Mouse also shares several physiological and pathological features with human, including cardiovascular, musculoskeletal, and other internal organ systems [29]. Additionally, the morbidity of mouse in research is relatively low owing to an extensively reduced healing time and superior immune *Animal Models in Medicine and Biology*

**2. Burn wound management**

the utilization of animal models has to be reproducible and as close as possible to burn lesions occurring in humans. Nevertheless, each animal model has advantages and limitations that determine its translational significance for burn treatments. In addition, the selection of the model should consider the anatomical and physiological characteristics of interspecies that reflect the differences in how different types of wounds heal and analytical techniques be applied. This chapter will further discuss the common animal models of burn injury as well as provide researchers with a better understanding of their benefits and limitations for the burn treatment

Burn injuries differ in their cause types and severity; hence, its treatment can be challenging to be managed. The first and second degrees of burn injuries usually are treated with the moisturizer, the topical agents, and/or an antimicrobial creams advised by the doctor [7]. This condition will typically heal within 2 weeks. On the other hand, because third degree of burn injuries destroys all of the skin layers, the majority of wound will tend to severely long-term consequences and cannot be managed by the primary healing process, so the additional surgical procedures, including skin grafting, skin substitutes, and the application of advanced wound dressing, are required [8, 9]. They act as filler to increase the dermal component of wound, improve the re-epithelization, and reduce the inhibitory factors and the inflammatory responses of wound healing, and therefore subsequent scarring [9, 10]. Numerous options for skin substitutes, dermal analogs, and advanced dressings existed, which can be broadly divided and utilized depending on the severity of burn injuries [11]. However, removing the eschar and covering the wound as early as possible are crucial since the main challenge in treating third degree of burn injuries is avoiding infection from any contaminations. In addition, appropriate deep burn care providing protection from physical damage and supporting the circulation of gas and moisture as well as a comfort to enhance the functional recovery

Advanced burn care has been associated with a deeper insight of the pathophysi-

Experimental model is essential when studying on the burns and its underlying mechanisms. Many animal models of burn injuries using mice, rats, rabbits, dogs, and pigs are reported. They have been widely used to examine the burn wound pathology, the effect of systemic drug application, local therapy, and the effect of burn trauma on the entire organism [14–16]. The use of animal models is considered suitable as valuable tools to examine the burn pathophysiology instead of *in vitro* experiment due to the heterogeneous nature of the burns and its similarity to the characteristics of the human skin. The accurate animal model that closely mimics the overlapping phases of severe burn wound would enable the researchers to investigate the potential of novel treatments and study each phase more precisely. However, each animal model of burn has its own advantages and limitations, so the evaluation of several models of burn wound in animals is important and will be

ology of burn wound healing as it demands the collaboration of many different tissues and cells that contribute to each phase of wound healing [12]. In severe burn, the phases of wound healing including inflammation, proliferation, matrix synthesis, and contraction, are dynamic and complex and tend to overlap [13]. Therefore, a better understanding of these phases is a key concept to continuously develop an

design that is proposed to be clinically applicable to humans.

should also be the priorities in severe burn wound care.

advanced severe burn wound management.

**44**

further described below.
