Delivery of Proangiogenesis Anti-miRs from Electrostatically Assembled Bandages for Diabetic Ulcers
Abstract
Diabetes is a disease that affects many Americans, and the number of patients with diabetes has increased as our population ages and lifestyles change. It is also a growing problem with military personnel and Veterans, with larger numbers suffering from diabetes than in the general population. A critical complication of diabetes is the development of diabetic ulcers, which are non-healing open wounds that appear on the extremities of diabetic patients. The resulting wounds become highly inflamed. High blood sugar levels lead to a cascade of biological conditions that reduce the effective blood vessels in the wound and the supply of oxygen and nutrients. Without oxygen and nutrients, the wounds are unable to regenerate and become resistant to deposition of new tissue. Various types of RNA molecules play a role in orchestrating the normal healing response through creation of new blood vessels, but in diabetes the levels of these RNAs may be different, contributing to impaired wound healing. When these wounds progress, they can become infected and may ultimately require amputation. In fact, diabetic ulcers are responsible for more than two-thirds of non-traumatic amputations in the U.S. Those with ulcers have higher rates of death than those who do not, highlighting the dangers of diabetic ulcers. Standard treatments for diabetic ulcers include surgical removal of affected tissue, cleaning of the wound, removing pressure from the wound, and eliminating infection. However, these treatments do not generally lead to complete wound closure, and alone are not sufficient to address advanced diabetic ulcers. More recently, commercial products have been developed, such as an ointment that contains a biochemical cue, known as a growth factor, to be released and stimulate the growth of healthy tissue. Although this approach can yield some improvement, it is less effective because the growth factor is largely cleared away early in the wound healing process. Furthermore, safety issues arise because large amounts of growth factor are used in comparison to what is actually needed, thus leading to side effects, including cancer. Other approaches require the use of living cells, which is costly and provides less flexibility in terms of storage and application of the treatment. Both treatments still only increase healing of ulcers from about 35% to 50%, leaving many without a viable treatment and highlighting the importance of developing new strategies to address diabetic ulcer healing. In the proposed work, we will study delivery of an inhibitor nucleic acid that can block the RNA molecules that may be implicated in impaired vessel formation in the wound. Different inhibitor nucleic acids can be combined to address different RNAs that may be blocking the formation of vessels. The combinations may promote more blood vessel generation than single inhibitor nucleic acids alone, potentially speeding the wound healing process. Ultimately, we aim to incorporate the inhibitor nucleic acids into a bandage. This bandage will be designed to gradually release the inhibitor nucleic acids and induce their release at the optimal time in the wound healing process. We will study the best combinations of inhibitors and the best timing for our bandage to release the nucleic acid therapies. To build this bandage, we will leverage a simple, water-based assembly method that can incorporate the inhibitor nucleic acids at high levels to form a film coating on a dressing. As the coating degrades, it will gradually release the inhibitor nucleic acids directly to the wound. While other therapies may be given as a pill that one takes by mouth or injection, our approach is local; one applies the bandage directly to the affected wound. In doing so, we can get more of our inhibitor nucleic acids to the area of the body that needs it and reduce the chances of side effects. The benefit of this work is the exploration of combinations of inhibitor nucleic acids that, wh
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110235
Entities
People
- Paula T. Hammond
Organizations
- Massachusetts Institute of Technology
- United States Army