Low-intensity vibration to improve healing of chronic wounds

低强度振动可促进慢性伤口的愈合

• 批准号: 10264788
• 负责人: Rhonda D Kineman
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-11-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10264788
• 关键词: Amputation; Area; Bandage; Bed rest; Blocking Antibodies; Blood; Blood Circulation; Cells; Chronic; Clinical; Data; Development; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetic mouse; Endothelial Cells; Epithelial Cells; Exposure to; Fibroblasts; Granulation Tissue; Growth Factor; Health; Healthcare Systems; High Fat Diet; Hospital Administration; Hospitalization; Human; Inflammatory; Insulin-Like Growth Factor I; Leg Ulcer; Liver; Mediating; Patients; Perfusion; Prediabetes syndrome; Prevention; Production; Quality of life; Signal Transduction; Skin; Somatomedins; Source; Spinal cord injury; Spinal cord injury patients; Testing; Tissues; Translations; United States Department of Veterans Affairs; Veterans; Wheelchairs; angiogenesis; chronic wound; cost; decubitus ulcer; diabetic; diabetic ulcer; healing; improved; keratinocyte; knock-down; mesenchymal stromal cell; migration; mouse model; non-diabetic; non-healing wounds; novel strategies; novel therapeutics; preclinical study; skin wound; vibration; wound; wound environment; wound healing

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.

抽象的 由糖尿病和脊髓损伤引起的大量慢性非治疗伤口以及 相关的截肢和退伍军人的生活质量降低代表了一个主要的健康问题 资深管理医疗系统。我们的早期研究表明，一种使用低 - 强度振动（LIV）促进组织灌注，肉芽组织形成和糖尿病的伤口愈合 老鼠。我们的数据进一步表明，LIV增加了血液中胰岛素样生长因子（IGF）-1的水平 伤口，因此IGF-1可能介导LIV诱导的愈合。我们的中心假设是LIV改善了伤口 通过增加的IGF-1活性在糖尿病的情况下进行愈合，这反过来刺激上皮的活性 细胞，内皮细胞，成纤维细胞以及促进愈合的杂质基质细胞。我们将测试这个 使用涉及糖尿病前和糖尿病小鼠模型的临床前研究的假设。在特定的目标1中， 我们将确定局部与全身LIV的相对效率改善伤口愈合。具体 AIM 2，我们将确定LIV是否通过增加系统性和/或局部生产IGF-1来改善愈合。 在特定的目标3中，我们将确定LIV是否通过IGF-1介导的MSC活性改善愈合。这 我们研究的影响在于LIV充当简单，安全，低成本和非成本的令人兴奋的潜力 侵入性治疗可增强组织灌注和伤口愈合。作为我们研究的一部分，我们将开发 可穿戴的压电LIV“绷带”，有可能快速翻译成廉价的患者 对照疗法。 LIV在糖尿病性溃疡的愈合之外可能还具有其他应用， 包括预防和/或治疗脊髓受伤和其他暴露的患者的压疮 长时间使用床头或轮椅。