Wednesday, January 15, 2025
1/15/2025
Summary Diabetic foot ulcers (DFUs) are a major complication of diabetes. These sores, if left untreated, can become infected and become a serious threat to the patient’s well being. Although the field of wound care management is well established, the effective treatment of chronic DFUs remains a challenge. The primary goal in the treatment of DFUs is for the wound to close as soon as possible and to do so in a durable way. However, prolonged inflammation, oxidative tissue damage, and impaired blood circulation in diabetic wounds delay the wound healing process, resulting in open, non-healing wounds that often lead to limb amputations. This proposal will address these problems by developing a versatile wound dressing that restores normal wound healing rates by reducing free radicals in the wound, providing a native-like scaffold for the cells to divide and migrate, and enhancing vascularization in the wound. Another problem is the inability to monitor the wound in real time after the patient leaves the hospital, leading to digit or limb amputations. We will address this problem by developing a wireless system that can monitor the temperature and pH of the wound in real time, parameters that have been shown to be indicators of infection. Therefore, the overall goal of this proposal is to develop a shape- conforming antioxidant dressing that upon exposure to body temperature transforms into a gel that promotes new tissue formation in diabetic wounds and a feedback system that involves tissue conforming sensors to monitor bacterial infection and/or lack of healing. Toward this goal, we have developed a novel macromolecule - poly (polyethylene glycol citrate-co-N isopropyl acrylamide) - that incorporates a laminin-derived peptide. This material, referred to as PPCN-A5G81, supports tissue regeneration and can conform to the unique shape and depth of a wound. As for wireless monitoring of the wound, we pioneered the development of flexible, stretchable electronic sensors that can be integrated with human skin or implanted into the body for continuous, non-invasive health monitoring and treatment of disease. We hypothesize that: 1) incorporating immobilized Cu2+ into PPCN-A5G81 will confer vasculoinductive properties that significantly increase PPCN-A5G81’s ability to restore normal healing rates of full thickness dermal wounds in diabetic mouse and swine models; and 2) conforming temperature and pH sensors are safe and can remotely provide real time information regarding blood perfusion and infection in dermal wounds in diabetic animals. The specific aims of this proposal are to: 1) fabricate a PPCN-based regenerative dressing with vasculoinductive, dermoconductive, and dermoinductive properties and investigate its safety and efficacy for healing full thickness wounds in diabetic mice and diabetic pigs with metabolic syndrome; and 2) fabricate and characterize telemetric wound feedback tissue-conforming sensors capable of measuring temperature and pH in infected and non-infected diabetic dermal wounds. Results from this research will contribute to the development of innovative clinical products that reduce amputation rates and improve patient outcome.
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