Abstract Large numbers of chronic non-healing wounds resulting from diabetes and spinal cord injury and the associated amputations and diminished quality of life for veterans represent a major health problem for the Veteran?s Administration healthcare system. Our early studies indicate that a novel therapy utilizing low- intensity vibration (LIV) promotes tissue perfusion, granulation tissue formation and wound healing in diabetic mice. Our data further indicate that LIV increases levels of insulin-like growth factor (IGF)-1 in blood and wounds and thus IGF-1 may mediate LIV-induced healing. Our central hypothesis is that LIV improves wound healing in the setting of diabetes through increased IGF-1 activity, which in turn, stimulates activity of epithelial cells, endothelial cells, fibroblasts as well as mesenchymal stromal cells that promote healing. We will test this hypothesis using preclinical studies involving mouse models of pre-diabetes and diabetes. In Specific Aim 1, we will determine the relative efficacy of local versus whole body LIV for improving wound healing. In Specific Aim 2, we will determine whether LIV improves healing by increasing systemic and/or local production of IGF-1. In Specific Aim 3, we will determine whether LIV improves healing via IGF-1-mediated MSC activity. The impact of our studies lies in the exciting potential for LIV to serve as a simple and safe, low-cost and non- invasive treatment for enhancing tissue perfusion and wound healing. As part of our studies, we will develop a wearable piezoelectric LIV ?bandage? that has potential for rapid translation into an inexpensive, patient controlled therapy. LIV could have additional applications over and above the healing of diabetic ulcers, including the prevention and/or treatment of pressure ulcers in spinal cord injured and other patients exposed to prolonged bedrest or wheelchair use.