Diabetic Wound Closure via Reengagement of a Pathway Required for Fetal Wound Healing
Abstract
This proposal is responsive to the FY20 PRMRP Topic Area of Diabetes, under the area of encouragement, “research on interventions to prevent or treat diabetes complications, including diabetic retinopathy, nephropathy, neuropathy, cardiomyopathy, and impaired wound healing.” Central Problem: One of the common complications associated with diabetes is non-healing chronic wounds. Despite many evolving innovative technologies and advances in endovascular surgical interventions, the morbidity and mortality of patients with diabetic foot ulcers (DFU) remains high and is escalating with the increased prevalence of diabetes. Innovation to overcome diabetic impairments to wound healing is needed. The prevalence of diagnosed diabetes in the military population enrolled in the MHS ranged from 7.3% to 11.2% in 2006 and from 8.3% to 13.6% in 2010. In 2010, the prevalence of diabetes among non-active military personnel were 13.3%-15.0% for those aged 45-64 years, 26.9%-32.9% for those aged 65-74 years, and 25.7%-31.5% for those aged 75 years and older. The Veterans Health Administration (VHA) estimates that around 25% of military veterans have diabetes compared with 9% of the civilian adult population. Veterans 65 years and older comprise 70% of those with diabetes and other diabetes associated complications. A 2016 study of diabetic foot ulcers (DFU) examined more than 66,000 veterans with type 2 diabetes and found the initial severity of the foot ulcer was a significant predictor of death, more so than coronary artery disease or stroke. The subjects were tracked for an average of 27.7 months, and the 1-, 2-, and 5-year survival rates were found to be 80.80%, 60.01%, and 28.64% respectively. These number suggests that despite many evolving innovative technologies and advances in endovascular surgical interventions, the morbidity and mortality of patients with DFU remains high and is escalating with the increased prevalence of diabetes. The economic burden of lower limb amputations in diabetic veterans was $206 million. Innovation to overcome the diabetic impairments to wound healing is needed. Innovation: In previous work, we have identified a molecular switch which, when activated, turns on a highly efficient pathway of tissue regeneration characteristic of fetal tissue and typically not seen in adult tissue. The innovation of this proposal is the successful engagement of fetal development pathway by application of topical nanotransfection technology in the context of adult diabetic wound healing. This pathway works across multiple organ system suggesting there is also potential for further development as therapeutic intervention in other disease conditions. Ultimate Applicability and Impact of Research: The observation that the proposed molecular switch works across multi-organ system broadens the applicability of the proposed research. Success of the proposed project will provide a new strategy to accelerate functional wound healing in adults suffering from diabetes using a fast onetime nanotransfection approach. The same principle can be applied to achieve better quality of healing that will prevent wound recidivism and infections in service members and war veterans with diabetes. Successful completion of this project has the potential to contribute significantly to both basic and translational research involving tissue regeneration. From a basic research standpoint, this project will establish the pathway by which wound healing can be achieved in diabetic adult conditions. This will also highlight potential roadblocks that need to be overcome to achieve successful tissue repair. At the translational research level, the project will also identify key molecules for pharmacological intervention for diabetic wound healing.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110097
Entities
People
- Chandan K Sen
Organizations
- Indiana University
- United States Army