Diabetes mellitus is widely acknowledged as one of the most prevalent metabolic diseases, affecting millions of people around the world. In addition to presenting the generally observed metabolic deficiencies, diabetes can also severely impact other body systems by impairing circulation, promoting neuropathy, and stalling the wound healing process. In particular, the cardiovascular system is often affected by diabetic co-pathologies;​ these can result from both impaired circulation and actual changes in the structure of cardiac tissue.

One such cardiac co-pathology is diabetic cardiomyopathy, or DCM. DCM presents primarily as impaired contraction of cardiac muscle in conjunction with progressive fibrosis, which is characterized by increased collagen deposition, increased cardiomyocyte apoptosis, and/or left ventricular hypertrophy. These observed effects are likely due to alterations within the diabetic microenvironment. Additionally, prior studies in the field of diabetic wound healing have shown that the hyperglycemic environment can alter the behavior of vascular cells, thus stalling the healing process in the chronic inflammatory phase. Since diabetic cardiomyopathy has been linked to increased occurrences of myocardial infarction and more severe post-infarct complications, there is a need for better therapeutic options than the currently employed treatment method, which relies solely on basic glycemic control.

This study explores the use of a bioengineered RAD16-II peptide nanofiber scaffold as a delivery vehicle for exogenous matrix metalloprotease 2 (MMP-2). This injectable scaffold/protein combination is suggested as a potential therapy for the severely fibrotic phenotype associated with diabetic cardiomyopathy since it has been shown that MMP-2 levels are reduced in diabetic cardiac tissue. Furthermore, MMP-2 primarily functions in maintaining the composition of the extracellular matrix by degrading fibrillar collagen;​ thus, decreased MMP-2 levels could be directly related to the observed fibrotic phenotype of DCM. Based on the data collected, nanofiberbased treatment provides a protective effect on cardiac functional parameters post-infarction under conditions of diabetic cardiomyopathy in a streptozotocin rodent model of type I diabetes. These observations are confirmed with immunohistochemistry results indicating that nanofiber treatment dramatically reduces formation of fibrous scarring after infarct while also increasing neovascularization within the infarcted scar area. Interestingly, the presence of differentiated macrophages at 8 weeks post-infarct also suggests the presence of continuous and active remodeling beyond the initial inflammatory response. Overall, the peptide nanofiber scaffold provides a suitable delivery vehicle for slow, controlled release of MMP-2 and appears to promote long-term tissue regeneration even after severe ischemic injury in the diabetic heart.