Partial-Thickness Wound Healing via Topical ATP Delivery

DESCRIPTION (provided by applicant): Autologous skin grafts are the preferred method for covering large burn surfaces. The healing of autologous skin grafts, and the re-harvesting of skin donor sites for autologous skin grafts, is often slowed by the altered metabolic state of burn victims. Accelerating the healing of the skin graft donor site would increase the number of sites that could be used and decrease the re-harvest time between grafts. One of the single most important factors in healing a skin graft donor site is the neovascularization and reestablishment of oxygen tension and nutrient levels in the wound. Ultimately the oxygen, and some of the nutrients, are used to produce adenosine triphosphate (ATP). ATP is used for nearly every aspect of the wound healing process, including protein synthesis, growth factor production, and mitosis. We have developed a technique for the rapid and controlled delivery of ATP using fusogenic lipid vesicles (VitaSol). VitaSol, when applied topically, provides wounds with ATP during hypoxic periods and accelerates the healing process of acutely wounded skin. The long-term objective of this proposal is to develop a safe and effective technique to accelerate the healing of partial-thickness wounds in swine using VitaSol, and prepare the compound for a Phase I clinical trial for autologous skin grafts. The specific aims of phase I project are: 1) Determine the mechanism by which VitaSol accelerates partial-thickness wound healing in swine. We hypothesize that the beneficial effects of increasing wound ATP levels are related to increased angiogenesis, increased angiogenic growth factor synthesis, and accelerated mitosis of keratinocytes and fibroblasts; 2) Optimize the formulation of VitaSol for maximal acceleration of partialthickness wound healing in swine. Once the mechanism of how VitaSol accelerates wound healing is known, the formulation will be mixed with an excipient to create a hydrogel which can be easily applied to wounds, and helps maintain ATP levels during a 24 hour period; and 3) Stabilize the optimized VitaSol formulation and examine efficacy in swine. The optimized VitaSol formulation will be prepared as freezedried powder and examined for stability and efficacy in partial-thickness wound healing. The success of this project is likely to have a major impact on medicine. It will enhance our understanding of how ATP delivery to wounds affects the wound closure rate and time to complete wound closure. Our paradigm shift in wound healing will provide a totally new therapeutic approach that could significantly increase number and frequency with which skin grafts can be harvested and used clinically.