Vasculogenic Skin Reprogramming to Rescue Diabetic Wound Healing
Abstract
This proposal addresses the FY20 Peer Reviewed Medical Research Program Topic Area: Diabetes – research on interventions to prevent or treat diabetes wound healing impairment. Rationale and Critical Problem to Be Addressed: Arm and leg extremity injuries sustained during military combat often include multiple tissue types, e.g., bone, blood vessels, nerves, and muscles. In the cohort of patients with such injuries, the principal aim of wound care is to reduce the amount of time necessary for wound closure, decrease the rate of infection, and reduce scarring that may be functionally limiting. Restoring blood supply at the injury site is a key driver of the overall repair process. Regenerative medicine offers novel therapeutic strategies. A critical challenge in wound healing is to restore blood supply to the ischemic wound site. Innovative approaches to wound healing and tissue regeneration are needed for combat wounds that are typically extensive and difficult to treat with conventional surgical and therapeutic techniques. Similarly, diabetics have impaired wound healing that can be life-threatening. Lower-extremity ulcers occur in 4%–10% of people with diabetes, with a lifetime risk that may be as high as 25%. An estimated 100,000 lower-limb amputations are performed annually on individuals with diabetes in the U.S. Interventions using well known inducers of angiogenesis have produced limited to no benefits in multiple clinical trials. Based on this premise, this proposal seeks to achieve successful vascularization of wounds utilizing novel regenerative principles. Innovation: The proposed technology, tissue nanotransfection (TNT) process takes less than a second and causes minimal discomfort. TNT technology has two major components. First, it is a nanotechnology-based device designed to deliver “cargo” (e.g., antisense oligonucleotides, ASO) to adult cells in the live body. Second, the specific biological cargo is inserted electrically into the tissue to trigger conversion of cells within the live body. This cargo, when delivered using the TNT device, converts an adult cell from one function to another. TNT is simple and rapid and may be implemented at the point of care. It does not require any laboratory-based procedures. The cargo is delivered in less than a second using short pulses with very low current that may cause a muscle to twitch but is barely felt by the subject. In its final form, the device will look like a handheld stapler equipped with microfluidics and power supply. The injectable (ASOmiR-200b) will be packaged in disposable cartridges, which will eject from the “stapler” after single use. Ultimate Applicability and Impact of the Research: Our strategy will focus on improving outcomes from extremity injury and blood flow defects, which strongly impact quality of life of affected civilians and combat personnel. Direct in vivo reprogramming has the potential to revolutionize treatments for extremity injuries with loss of blood flow by enabling the use of the patient’s own tissue as a factory to produce different types of cells required to heal conditions locally or at other sites on the same body. TNT can help generate cells and tissues of therapeutic interest, within the patient’s own body, eliminating the need for immune suppression and lengthy laboratory-based expensive procedures. The penny-sized device (pad) is placed on the tissue and the device is zapped with a small electrical charge that is barely felt by the patient. This injects genes into the area and the existing tissue (e.g., skin, muscle, etc.) is changed in such a way as to acquire the temporary ability to rescue injured tissues or organs by increasing blood flow. This technology could potentially be used for many different types of applications from healing injuries to combating aging.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110033
Entities
People
- Chandan K Sen
Organizations
- Indiana University
- United States Army