Chronic wounds are projected to reach epidemic proportions worldwide because of the aging population and the increasing incidence of diabetes. It is estimated that 25% of diabetics develop foot ulcers, and these ulcers are estimated to have a cost of $9 to $13 billion in the U.S. alone. Many of these wounds are infected by bacteria including antimicrobial-resistant organisms like methicillin-resistant Staphylococcus aureus (MRSA). Thus, there is a critical need to develop improved dressings to treat chronic wounds, including those infected with MRSA, lest the clinical and financial burdens of chronic leg wounds continue to grow exponentially. Our long-term goal is to engineer superior dressings to improve healing of chronic wounds complicated with infection. We9 and others10 have demonstrated that the compound gallium maltolate (GaM) has antimicrobial activity against MRSA, even when a biofilm is formed. The full impact of GaM on cellular actions has not been elucidated but at appropriate doses gallium promotes collagen synthesis and cell migration, favorably modulates integrin expression.14-15 Notably, our preliminary results indicate that the net effect of a GaM ointment is to enhance these aspects of healing in a large animal model of chronic, infected limb wounds. Although this study provided proof-of-concept for the utility of GaM, there are a number of limitations in using an ointment to treat chronic wounds including poor dose control and need for frequent re-application due to poor residency. The objective of this project is to provide evidence that a GaM-releasing hydrogel foam can improve outcomes over current antimicrobial dressings. Our central hypothesis is that a hydrogel foam dressing which provides appropriate delivery of GaM and improved moisture control will promote healing of infected chronic wounds. Our rationale for these studies is that demonstrating efficacy of this hydrogel foam dressing will lead to improved treatment options (innovation) and elucidation of GaM-initiated cellular mechanisms in chronic wound healing (new knowledge). Completion of these studies will establish the benefit of gallium maltolate (GaM) as a new and effective antimicrobial agent and elucidate its effect on key cellular processes. This study will also assess initial efficacy of an improved dressing to reduce treatment costs and reduce morbidity/mortality associated with chronic wounds including limb amputations.
The proposed research is relevant to public health because therapeutic options for chronic wounds remain limited, and these wounds are associated with a variety of chronic diseases and conditions (diabetes, ageing, obesity, scleroderma, etc.), many of which are increasing in prevalence. The proposed research is further relevant to public health in addressing a novel therapeutic for chronic staphylococcal skin infections. Thus, the proposed research is relevant to the part of NIH's mission that pertains to controlling morbidity and health care costs associated with diabetes, other metabolic disorders including obesity, peripheral vascular diseases, and the spread and transmission of antimicrobial resistant organisms like MRSA.
