(WHS-P94) A new treatment for long-term diabetic wounds
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
Background In medicine, the treatment of diabetic wounds is one of the most difficult to get good results. Despite thousands of wound dressings developed in the past century, none has shown any good effect to enhance the healing process, including the only FDA-approved prescription growth factor, Regranex. Multiple factors contribute to nonhealing diabetic wounds, and many of the pathways involved are not entirely clear. Surgeons have long recognized that ischemic tissues heal poorly and are easily infected. One direct effect of ischemia is a reduction of tissue high energy phosphate reserve. Methods We have developed an intracellular ATP delivery (ATP-vesicles) to enhance wound healing by providing direct high energy phosphate. When used in animal experiments, it has shown extremely rapid tissue regeneration—granulation tissue starts to appear very quickly after surgery. We hypothesized that tissue ischemia was one major contributing factor in diabetic wound healing, and if exogenic energy is provided, healing should be enhanced. Twenty-five diabetic rabbits were used in this study. Diabetes was induced by alloxan (100 mg/kg) IV injection. After stable diabetes was established, the rabbits were kept for 3-12 months before wound study. In each rabbit, the left ear was made ischemic using vascular disruption or adding a silicone ring buried in the ear base to limit vessel and nerve regeneration. The right ear vessel and nerve supply was not disturbed as normal control. Four wounds (5 mm in diameter) were created on the ventral side of each ear, resulting in 100 ischemic wounds and 100 non-ischemic wounds. On each ear, the two wounds on one side were treated with ATP-vesicles while the other two wounds were treated with Regranex (50 for ATP-vesicles and 50 for Regranex). Results Many of the wounds treated by ATP-vesicles started to have new growth only 1 to 2 days after surgery while the wounds treated by Regranex did not have new growth before day 5. The wounds treated by ATP-vesicles were healed much faster than the wounds treated by Regranex. Histologic study shows that the use of ATP-vesicles increased tissue collagen production quickly and this was accompanied by very early and massive platelet trafficking followed by massive macrophage accumulation and rapid direct collagen production, resulting in much faster wound healing. Conclusion Our results show that using intracellular ATP delivery can enhance wound healing in long-term diabetes, and this is accompanied by rapid macrophage accumulation, in situ proliferation, and direct collagen production.