PROJECT SUMMARY Chronic diabetic wounds (CDW) are one of the most challenging and common medical complications of type-2 diabetes. CDWs are associated with significantly increased costs for healthcare systems and society, decreased quality of life for patients, higher rates of co-morbidities such as recurrent infections and amputations, and an overall dramatically higher mortality rate. The wide prevalence of type-2 diabetes and its constantly increasing impact urgently demand the need for effective treatments aimed at restoring physiological healing of CDWs and preventing associated co-morbidities and mortality. Insufficient skin vascularization and infection inhibit effective healing of CDWs. In non-diabetic injuries, physiologic healing relies on neoangiogenesis and vascularization to restore tissue oxygenation, provide metabolic support to regenerating cells/tissues, and to allow migration of immune cells to counteract pathogens. Instead, in CDWs angiogenesis is impaired resulting in tissue hypoxia, lack of the metabolic support required for tissue repair, and an insufficient immune-response to bacterial infections. These conditions first “lock” CDWs in a chronic inflammatory state unable to progress to tissue repair and second place the patients at risk of sepsis. In severe cases, surgical debridement or limb amputation is the only option for saving patients’ lives. Our hypothesis is that the delivery of VEGF (an angiogenic factor), oxygen combined with on demand release of antibiotics in response to upregulation of neutrophil secretomes can prevent biofilm formation and in turn can reduce the CDW morbidity rate. The goal of this proposal is to engineer bandages containing microneedle arrays that can control release VEGF, oxygen, and can self respond to upregulation of bacteria mediated neutrophil secretomes for inducing healing and avoiding infection.