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.
Public Health Relevance Statement: NARRATIVE Diabetic foot ulcers (DFUs) are the leading cause of nontraumatic lower extremity amputations but effective treatment is still lacking. In this proposal, we will use our newly developed intracellular ATP delivery for wound care in a newly developed long- term diabetes plus ischemia and neuropathy, and to test its toxicity in preparation for FDA approval. The success of the project will have a major contribution to medicine.
Project Terms: Red Cell; blood corpuscles; Fibrin; Fibroblasts; Granulation Tissue; Growth; Generalized Growth; Tissue Growth; ontogeny; Cyclic GMP; Guanosine Cyclic Monophosphate; cGMP; Recording of previous events; History; Hospitalization; Hospital Admission; Human; Modern Man; Human Volunteers; Ischemia; Lower Extremity; Lower Limb; Membrum inferius; Lipids; macrophage; MÏ; Medicine; Play; Production; Recurrent; Recurrence; Testing; Time; Tissues; Body Tissues; Genetic Transcription; Gene Transcription; RNA Expression; Transcription; United States; wound healing; Wound Repair; wound resolution; Hypertrophic Cicatrix; Hypertrophic Scars; Clinical; Phase; diabetic; Vesicle; Diabetes Complications; Diabetes-Related Complications; Diabetic Complications; Complications of Diabetes Mellitus; Recombinant Platelet Derived Growth Factor Beta Chain; Regranex; rhPDGF-BB; Becaplermin; Hour; neuropathic; Neuropathy; In Situ; Normal saline; Techniques; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; success; Animal Models and Related Studies; model of animal; model organism; Animal Model; Toxicities; Toxic effect; Reporting; Effectiveness; diabetic foot wound; Diabetic Foot Ulcer; Preparation; Process; tissue regeneration; regenerate new tissue; regenerate tissue; regenerating damaged tissue; regenerating tissue; tissue regrowth; tissue renewal; tissue specific regeneration; healing; Outcome; wound; tissue wound; wounding; wounds; innovation; innovate; innovative; commercialization; FDA approved; effective therapy; effective treatment; preclinical toxicity; pre-clinical toxicity; phenome; Growth Factor; Growth Agents; Growth Substances; Proteins Growth Factors; wound care; wound assessment; wound monitoring; effectiveness testing; Wound models; wound healing models; Amputation; Animals; Blood Platelets; Marrow platelet; Platelets; Thrombocytes; Clinical Trials; Collagen; Communities; Diabetes Mellitus; diabetes; Sterile coverings; Dressing; Erythrocytes; Blood erythrocyte; Erythrocytic; Marrow erythrocyte; Red Blood Cells
