Animal models in burn research

Abstract

Burn injury is a severe form of trauma affecting more than 2 million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury, to elucidate the pathophysiology, and to explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research.

Fig. 1

Experimental steps in the burn rodent model and histological images of C57/BL mice skin subjected to full-thickness burn (30 %TBSA). a The rodent is anesthetised with an intraperitoneal injection of Xylazine and Ketamine. b The area (dorsum) to be burned is shaved with a clipper to ensure an even burn. c The rodent is then placed in a flame-resistant mold with an opening exposing a pre-determined total body surface area to burn; the exposed area is then immersed in a 100 °C water bath for 8 s. d Lactated Ringer’s solution is then administered intraperitoneally for resuscitation; buprenorphine or other analgesia may be administered subcutaneously for pain control. Excised burned skin tissue specimens from burned mice (thickness = 5 μm) were harvested and then Masson’s trichrome staining performed. e Intact skin showing histological component of mouse non-burned skin. f Burned skin harvested from mouse 48 h post-burn. Note that the animal is presenting with complete destruction of skin, most obviously in the epidermal/dermal segments. g Animal at 2 weeks post-burn showing signs of wound healing: re-epithelialization (at wound edge), neovascularization, and formation of new granulation tissue. Arrows indicate wound edges or new granulation tissue formation. Collagen fibers in the dermis are stained in blue, epidermis and muscle stained in red

Fig. 2

Trends and costs associated with animals in burn research, showing the total number of articles appearing in the PubMed database for each species by year of publication. a The popularity of the rat as the species of choice in burn studies during the last century declined in the mid-2000s when the mouse research overtook the amount of burn research in rat. b The cost of purchase, delivery, and housing for 30 days of a pig, rat, and mouse used in burn research (in Canadian dollars). Costs were calculated based on the quotes and housing fees of the animal facility here at Sunnybrook Health Sciences Centre, Canada. Precise costs will differ from one facility to another; however, the trend remains the same with regards to inter-species cost differences