Low-intensity vibration to improve healing of chronic wounds

摘要 糖尿病和脊髓损伤导致的大量慢性不愈合伤口以及 相关的截肢和退伍军人生活质量的下降是一个主要的健康问题， 退伍军人管理局的医疗保健系统。我们早期的研究表明，一种利用低- 强度振动（LIV）促进糖尿病患者组织灌注、肉芽组织形成和伤口愈合 小鼠我们的数据进一步表明，LIV增加血液中胰岛素样生长因子（IGF）-1的水平， 因此IGF-1可以介导LIV诱导的愈合。我们的中心假设是LIV改善伤口 通过增加IGF-1活性，从而刺激上皮细胞的活性， 细胞、内皮细胞、成纤维细胞以及促进愈合的间充质基质细胞。我们将测试这个 使用涉及糖尿病前期和糖尿病小鼠模型的临床前研究的假设。具体目标1、 我们将确定局部与全身LIV改善伤口愈合的相对功效。在特定 目的2，我们将确定LIV是否通过增加全身和/或局部IGF-1的产生来改善愈合。 在具体目标3中，我们将确定LIV是否通过IGF-1介导的MSC活性改善愈合。的 我们的研究的影响在于令人兴奋的潜力，LIV作为一个简单，安全，低成本和非 用于增强组织灌注和伤口愈合的侵入性治疗。作为我们研究的一部分，我们将制定一个 可穿戴的压电LIV“绷带”，具有快速转化为便宜的患者的潜力， 控制治疗LIV可以在糖尿病溃疡愈合之外有其他应用， 包括预防和/或治疗脊髓损伤和其他暴露患者的压疮 长时间卧床或使用轮椅。

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.