( Non-healing wounds caused by diabetes mellitus account for one of the most common complications of this disease leading to increased healthcare cost, decreased quality of life, infections, amputations, and death. The wide prevalence of this disease and its projected increase in the near future has further necessitated therapeutics aimed at enhancing the healing of diabetic wounds. Vascularization and oxygenation are critical parameters in wound healing process. In healing tissue, sufficient oxygenation is critical because of the increased energy demand for reparative processes such as cell proliferation, bacterial defense and collagen synthesis. In normal acute wounds, neoangiogenesis and vascularization result in tissue oxygenation. However, in chronic diabetic wounds, angiogenesis is impaired; thus, severe hypoxia results in insufficient energy for healing, excessive inflammation, and bacterial infection. Although exogenous vascular endothelial growth factor (VEGF) has shown to improve neoangiogenesis, the lack of oxygen significantly reduces the healing rate. Our hypothesis is that the proper oxygenation of wound combined with the delivery of angiogenic factors such as VEGF will enhance the healing process and enable the immune cells to eradicate colonized pathogens. Our approach is to make a smart wound dressing by continuously monitoring epidermal oxygen concentration in the wound area as a measure of angiogenesis and locally releasing VEGF and oxygen which are essential for the healing process on demand. In addition to improve the effectiveness of the therapy and accuracy of measurements, we proposed to bypass the debridement by using microneedles which have already proven to be more effective. We propose to develop this advanced and clinically relevant technology using the following steps: 1) fabricating VEGF eluting microneedles on a flexible substrate; 2) engineering microneedle-based oxygen sensors as well as flexible oxygen generation and delivery modules and their integration; and 3) evaluate the in vivo functionality of the engineered platform in diabetic wound models. The proposed design not only could sense the wound environment, but also can control release VEGF and modulate the tissue oxygenation.

Public Health Relevance

Chronic wounds do not heal in a timely and orderly fashion. Approximately 7 million patients are affected by chronic wounds including diabetic ulcers in the United States alone, and an estimated $25 billion dollars is spent annually on the treatment of these wounds. One of the key challenges in healing of diabetic ulcers is lack of angiogenesis and vasculogenesis which limits the access of nutrients, migratory cells, and oxygen to the damaged tissue. In this proposal, we aim to develop a smart wound dressing that can delivery oxygen and angiogenic factors and monitor the healing process. This smart platform can monitor transdermal oxygen levels in a continuous manner and is also capable of transdermal delivery of oxygen and controlled-release of VEGF.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Instrumentation and Systems Development Study Section (ISD)
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Wolfson, Michael
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Brigham and Women's Hospital
United States
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