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可愈合伤口和 相关截肢和退伍军人生活质量下降是退伍军人面临的一个主要健康问题 退伍军人管理局医疗保健系统。我们早期的研究表明，一种新的治疗方法利用低- 强度振动(LIV)促进糖尿病患者组织灌注、肉芽组织形成和创面愈合 老鼠。我们的数据进一步表明，LIV增加了血液和血液中胰岛素样生长因子(IGF)-1的水平 创伤和IGF-1可能介导LIV诱导的愈合。我们的中心假设是Liv可以改善伤口 糖尿病的愈合通过增加IGF-1活性，进而刺激上皮细胞的活动 促进愈合的细胞、内皮细胞、成纤维细胞以及间充质基质细胞。我们将对此进行测试 假设使用临床前研究，涉及糖尿病前期和糖尿病的小鼠模型。在具体目标1中， 我们将确定局部和全身LIV在促进伤口愈合方面的相对疗效。具体而言 目的2，我们将确定LIV是否通过增加全身和/或局部IGF-1的产生来促进愈合。 在具体目标3中，我们将确定LIV是否通过IGF-1介导的MSC活性促进愈合。这个 我们研究的影响在于LIV作为一种简单安全、低成本和非 侵入性治疗，以增强组织灌流和伤口愈合。作为我们研究的一部分，我们将开发一种 可穿戴的压电式Liv“绷带”，有可能迅速转变为廉价的患者 控制性治疗。除了治疗糖尿病溃疡之外，LIV还可以有更多的应用， 包括预防和/或治疗脊髓损伤和其他暴露的患者的压疮 长时间卧床或轮椅使用。

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.