Impaired wound healing represents a major morbidity for diabetic patients, representing for more than 60% of non-traumatic lower-limb amputations.  Insufficient neovascularization is a major factor contributing to impaired wound healing in diabetic ulcers.  Two major mechanisms that may be responsible for the deficiency in neovacularization are 1) adverse angiogenic environment caused by increase protease activity and matrix degradation, which, in turn, may lead to cell apoptosis and insufficient recruitment of endothelial cells (ECs) and endothelial precursor cells (EPCs), and 2) altered cell phenotype in ECs which affect their activities in response to the cytokines and other growth factors. 
Although there have been several studies characterizing diabetic-associated changes in fibroblast phenotype and inadequate matrix deposition, not much is known about the effects of diabetes on the phenotype of ECs and their angiogenic potentials.  This information is important to develop new therapies that enhance angiogenesis and healing of chronic diabetic ulcers. 
Our previous studies demonstrated that a self-assembling peptide nanoscaffold provides an angiogenic environment that enhances survival of endothelial cells and angiogenesis both in vitro and in vivo in a mouse model of type II diabetes.  However, in order to fully utilize the potential of the nanoscaffold for development of treatment for diabetic ulcers in human patients, it is necessary to understand the mechanisms of its action, especially with ECs.  Thus the objectives of this study are:

1. To compare the difference in angiogenic potential between the diabetic and non-diabetic microvascular endothelial cells, 
   
2. To elucidate how the peptide nanoscaffold interacts with the microvascular endothelial cells to enhance the angiogenesis.