Wound infection is a major complication in diabetic patients[
1]. According to the American Diabetes Association, 25% of people with diabetes will suffer from a wound problem during their lifetime, and it has been estimated that lower limb amputations in diabetic patients account for >60% of all amputations performed[
2]. Patients with diabetes have impaired wound healing associated with multitude of factors, including neuropathy, vascular disease, and foot deformities[
3,
4]. At the cellular level, an increase in the number of acute inflammatory cells, absence of cellular growth, and migration of the epidermis have been observed[
5]. Patients with diabetes have impaired leukocyte function, and the metabolic abnormalities of diabetes lead to inadequate migration of neutrophils and macrophages to the wound, along with reduced chemotaxis[
6,
7]. Such cellular changes would predispose individuals to an increased risk of wound infection.
Staphylococcus aureus (
S. aureus) is the most common single isolate (76%) in diabetic wounds and foot ulcers and leads to alterations in wound healing[
8]. Wound infection can also result in bacteremia or sepsis and is associated with high morbidity and mortality[
9]. In the United States
S. aureus is the most common cause of skin and soft-tissue infections, as well as of invasive infections acquired within hospitals[
10,
11]. Treatment of severe
S. aureus infections is challenging, and the associated mortality rate remains high [
12,
13].
S. aureus is a gram-positive bacterium that colonizes the skin and is present in the anterior nares in about 25–30% of healthy people[
14]. Over the last 40 years methicillin-resistant
S. aureus (MRSA) infections have become endemic in hospitals in the U.S. and worldwide[
15]. In 2002, the first clinical isolate of vancomycin-resistant
S. aureus (VRSA) was identified in a patient with diabetic foot ulcer[
16]. The progressive reduction of therapeutic efficacies of the available antibiotics underlines the need for the development of new therapeutic strategies for the treatment of infected wounds. However, little is known about the biology of infections in diabetic wounds, and there are no suitable animal models. No large animal studies have been performed, since there is no infected diabetic large animal model available. Small mammals such as rats, rabbits, and mice are frequently used in wound healing studies because of cost and ease of handling[
17]. Nevertheless rodents are not optimal for
in vivo wound healing studies because of distinct differences with humans in terms of anatomy and wound-healing physiology. In contrast, pig skin resembles human skin anatomically and physiologically[
18], and porcine wound healing has been found to be significantly similar to that of humans[
19,
20]. Furthermore, the overall physiology of pigs is close to that of humans, including the anatomy and function of most key organ systems. Sullivan et al evaluated 25 different wound therapies and showed that, in studies that could be compared to human studies, the results in porcine models agreed with those of human studies 78% of the time, whereas results of small-mammal models showed only 53% agreement[
21]. Thus, the many similarities between humans and pigs have led to the conclusion that the pig could provide a suitable model in which to study infected diabetic wound healing. Moreover, the possibility of creating multiple experimental wounds in a single animal reduces the interindividual variability that weakens other wound infection models. Some porcine models for wound healing studies have been reported previously, specifically with non-diabetic burn wounds[
22,
23] and excisional wounds[
18,
24]. We previously developed an external polyurethane chamber that can be sealed around the edges of the wound [
25,
26]. The chamber protects the wound like a dressing but allows the wound environment to be standardized and monitored and provides access for controlled delivery of bacterial strains or potential therapeutic agents. It also allows collection and monitoring of wound fluid for further analysis such as bacterial quantification, growth factor and cytokine analysis, or gene expression as well as assessment of wound contraction and reepithelialization.