Developing a new DFU dressing

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ABSTRACT Diabetic foot ulcers (DFUs) are the leading cause of nontraumatic lower extremity amputations in the United States and are responsible for more hospitalizations than any other complication of diabetes. Despite thousands of dressings developed in the past century, none have shown any specific effectiveness as DFU treatments. Currently, even the best available treatments achieve only a 50% healing rate for these wounds—and this healing is often temporary, with a 66% chance of recurrence. For the first time in history, we have found an approach that may change the current dogma. We have developed a technique for intracellular ATP delivery (ATP-vesicles or VitaSol™). When we use VitaSol™ for wound healing, granulation tissue starts to appear within 24 hours. This new tissue keeps growing and fills the wound cavity within a few days, a phenomenon never seen or reported before by any other techniques. Control dressings, including normal saline, free Mg-ATP, empty lipid vesicles, and the only FDA-approved prescription growth factor, Regranex, have no such effects. The final healing time is much shorter than the controls in long-time diabetic plus ischemic wounds. A preliminary mechanistic study has shown that the extremely rapid tissue regeneration is the result of very early (5 hours after surgery), rapid, and massive macrophage accumulation, in situ proliferation, M2 polarization, and direct collagen production, long before traditional fibroblasts come into play. This type of healing is totally different from the conventional process known to the wound care community, where fibrin, platelets, and red blood cells are the main components of the early provisional matrix, which is gradually replaced by granulation tissue during the proliferation phase after 3–6 days of lag time. Although the growth seen with VitaSol™ is extremely rapid, it does not display any unusual growth or hypertrophic scar formation after 2 years in animals and after more than 9 years in limited human volunteers. If this can be duplicated in humans, it will be a major breakthrough in medicine. Our central hypothesis is that intracellular ATP delivery provides critical energy at very early time, activates various transcription mechanisms, resulting in extremely early and rapid tissue regeneration that fills the wound cavity quickly. In this proposal, we will perform a preclinical toxicity study aimed at IND application, and test the effectiveness of VitaSolTM in a new animal model with long-term diabetes, ischemia, and neuropathy. Our product for intracellular energy delivery has consistently been viewed as innovative. The outcome of this project will be the clinical introduction of a highly effective, inexpensive, and easy-to-use new dressing for DFU treatment. The potential impact is very high.