Background: Diabetes is one of the fastest increasing diseases in aging societies across the world including the U.S. Approximately 30.3 million Americans have diabetes, including an estimated 7.2 million who have the disease but have not received a diagnosis. Diabetes is associated with multiple chronic conditions, among which impaired wound healing, and associated complications pose significant clinical challenges both in terms of successful treatment as well as compromised well-being of diabetes patients. The estimated annual cost of diabetes on the U.S. healthcare system overall is $245 billion. While diabetes inflicts tremendous clinical and economic burdens across diverse population groups, Veterans as a population group face particularly devastating suffering from diabetes. The U.S. Department of Veterans Affairs (VA) reports that nearly one in four Veterans (24%) have diabetes, significantly surpassing the 9% diabetes patients in the U.S. civilian population.

Among various complications of diabetes, diabetic foot problems represent one of the major complications that significantly impair the quality of life of diabetic patients and lead to more than 750,000 new diabetic foot ulcers (DFU) and 70,000 lower extremity amputations per year in the U.S. alone. The unique pathological nature of DFU with significantly impaired wound healing capability renders it greatly challenging condition to treat. Despite various therapeutic approaches, including growth factors and regeneration grafts, having been clinical tried both on animals and human patients, the existing solutions have failed to show meaningful efficacy on improved healing of diabetic ulcer such as DFU. These daunting yet ongoing challenges clearly underscore the significant needs to develop novel breakthrough therapies as indicated in the FY20 PRMRP Topic Area: “Research on interventions to prevent or treat diabetes complications, including diabetic retinopathy, nephropathy, neuropathy, cardiomyopathy, and impaired wound healing.”

Proposed Solution: In this proposed project, our team proposes a novel therapeutic platform for accelerated healing of diabetic ulcers based on a strain-programmable bioadhesive patch. The proposed strain-programmable bioadhesive patch possesses a set of unique and readily translatable capabilities including:

• Rapid, robust, and on-demand detachable adhesion on wet diabetic wounds.

• Facile and preparation-free easy application.

• Precisely tunable contraction and mechanical modulation of diabetic wounds.

• Accelerated closure and healing of diabetic wounds by highly optimized mechanical modulation.

Team and Impact: The proposed project will leverage the synergistic combination of expertise of Initiating PI (Dr. Zhao) and Partnering PI (Dr. Veves) with extensive experience and leadership in materials science and engineering, treatment of diabetes patients including DFU, and established preclinical animal models for diabetic wound healing. In particular, the project will significantly benefit from Partnering Principal Investigator Dr. Veves’s expertise and rich resources in the clinical treatment of diabetic patients at Joslin-Beth Israel Deaconess Foot Center. In addition, strong in vitro, ex vivo, and in vivo preliminary data and the carefully engineered composition and fabrication process of the bioadhesive patch will help in the translation of this technology for clinical applications to benefit both civilians and Veterans.