Many wounds, such as surgical and traumatic injuries, heal without difficulty. Chronic wounds, however, typically exhibit delayed healing in patients with underlying medical conditions that prevent normal tissue repair. For example, approximately 15% of all people with diabetes mellitus will develop a foot ulcer at some point in their lives. Diabetic foot ulcers have an increased risk of infection due to the slow healing times caused by poor blood circulation in the extremities and other associated co-morbidities. The treatment of diabetic foot ulcers is further complicated by the presence of multidrug resistant pathogens like MRSA methicillin resistant Staphylococcus aureus) and Pseudomonas aeruginosa. If left untreated, contaminated foot ulcers routinely become clinically infected and may ultimately lead to lower-limb amputations. This Phase II aims to develop a topical wound dressing that functions safely and effectively to prevent these and other chronic wound infections. Novan, Inc. was founded to commercialize an innovative platform technology that harnesses the anti-infective power of nitric oxide (NO). During Phase I, Novan successfully created polyurethane films containing nitric oxide-loaded precipitated silica (Nitricil(tm)) that exhibit broad spectrum efficacy against Gram-negative and Gram-positive bacteria, including P. aeruginosa. Following extensive discussions with clinicians and a thorough assessment of advanced wound care products utilized to manage infection, the goal of this three17 year project is to manufacture an absorbent nitric oxide-releasing wound dressing called Nitrisorb(tm). The specific aims for this project are to 1) optimize the dose of Nitricil(tm)-loaded in the wound contact layer, 2) produce commercially viable wound dressing prototypes, and 3) evaluate Nitrisorb(tm) product performance and safety in vivo. The Nitrisorb(tm) product could lead to a significant reduction in the costs of chronic wounds by improving the healing time, reducing the number of hospital days, and decreasing the number of procedures required to treat infections. The only FDA approved use of NO is as a drug in the gaseous form to treat pulmonary hypertension in neonates (INOmax, 1999). The unprecedented use of NO in a wound dressing dictates the submission of a Request for Designation (RFD) to the FDA's Office of Combination Products. A formal response will designate the regulatory jurisdiction and path required to obtain product approval (i.e., drug, device, or biologic). Ultimately, Novan aspires to commercialize the first NO-based wound dressing. The Company has assembled a strong team of scientists, clinicians, contractors, and business leaders who believe in the technology and are positioned to ensure the greatest likelihood for success. PUBLIC HEALTH RELEVANCE: Many wounds, such as surgical and traumatic injuries, heal without difficulty. Chronic wounds, however, typically exhibit delayed healing in patients with underlying medical conditions that prevent normal tissue repair. For example, approximately 15% of all people with diabetes mellitus will develop a foot ulcer at some point in their lives. If left untreated, contaminated foot ulcers routinely become clinically infected and may ultimately lead to lower-limb amputations. The goal of this Phase II project is to develop an absorbent nitric oxide-releasing wound dressing (Nitrisorb") that functions safely and effectively to prevent these and other chronic wound infections.