Mechanisms for Wound Healing with Ultrasound

描述（由申请人提供）：迫切需要新的破坏性技术来加速或改善慢性软组织伤口的愈合。慢性伤口，包括糖尿病溃疡、腿部溃疡和压疮，在全球范围内造成了巨大的医疗保健负担。目前，慢性伤口治疗主要是支持性的。有效刺激特定伤口愈合途径的新型治疗方法将大大降低医疗保健和经济成本，减少截肢的机会，并改善慢性伤口患者的生活质量。细胞外基质（ECM）提供了一系列复杂的细胞粘附位点、细胞迁移途径和细胞增殖信号，并赋予愈合伤口机械稳定性。机械力影响ECM纤连蛋白原纤维的沉积、组织和结构，这进而影响细胞功能、ECM组织和稳定性、组织拉伸强度和血管灌注。超声（US）目前在临床上用于促进骨愈合，并已被证明可以增强软组织修复。已知超声的某些生物效应通过非热机械机制发生。因此，我们假设与超声传播相关的机械力能够重塑慢性伤口中的纤连蛋白，以暴露生物活性部位，进而增强肌成纤维细胞的生长和收缩性，刺激上皮细胞迁移，促进胶原组织化和机械强度，并增加组织的血流。在这项提案中，我们组建了一个由科学家、工程师和临床医生组成的多学科团队，他们拥有细胞和ECM生物学、生物医学超声和声学、血管生物学和伤口愈合方面的专业知识。我们将使用非侵入性超声场来确定超声增强软组织伤口愈合的关键生物和物理机制，以开发超声在慢性伤口治疗中的应用。基本机制的知识提供了设计优化的暴露参数，识别协同疗法和设计暴露系统的力量，这些暴露系统最大限度地提高了US的治疗效果，同时最大限度地减少了不良副作用。 公共卫生相关性声明（由申请人提供）：慢性伤口，包括糖尿病性溃疡、腿部溃疡和压疮，在全球范围内造成了重大的医疗保健负担。需要新的治疗方法来快速闭合烧伤和慢性伤口，防止感染和液体流失，并促进自然愈合过程。在这个建议中，我们开发了非侵入性超声场的使用，以加速组织修复。

DESCRIPTION (provided by applicant): There is a critical need for new disruptive technologies to accelerate or improve the healing of chronic soft tissue wounds. Chronic wounds, including diabetic, leg, and pressure ulcers, impose a significant health care burden worldwide. Currently, chronic wound therapy is primarily supportive. Novel treatments that effectively stimulate specific wound healing pathways would greatly reduce healthcare and economic costs, lessen the chance of amputation, and improve the quality of life of patients with chronic wounds. The extracellular matrix (ECM) provides a complex array of cell adhesion sites, cell migration pathways, and proliferation signals to cells, and imparts mechanical stability to the healing wound. Mechanical forces influence the deposition, organization, and structure of ECM fibronectin fibrils, which in turn, affects cell function, ECM organization and stability, tissue tensile strength, and vascular perfusion. Ultrasound (US) is currently used clinically to promote bone healing and has been shown to enhance soft tissue repair. Certain biological effects of US are known to occur through non-thermal, mechanical mechanisms. Thus, we hypothesize that mechanical forces associated with US propagation are capable of remodeling fibronectin in chronic wounds to expose biologically active sites that, in turn, enhance myofibroblast growth and contractility, stimulate epithelial cell migration, promote collagen organization and mechanical strength, and increase blood flow to tissues. In this proposal, we have assembled a multidisciplinary team of scientists, engineers, and clinicians with expertise in cell and ECM biology, biomedical ultrasound and acoustics, vascular biology, and wound healing. We will use noninvasive US fields to identify key biological and physical mechanisms for US-enhanced soft tissue wound healing in order to develop the use of US for chronic wound therapy. Knowledge of basic mechanisms provides the power to design optimized exposure parameters, identify synergistic therapies, and engineer exposure systems that maximize the therapeutic effects of US while minimizing adverse side effects. Public Health Relevance Statement (provided by applicant): Chronic wounds, including diabetic, leg, and pressure ulcers, impose a significant health care burden worldwide. New treatment methods are needed to rapidly close burns and chronic wounds, prevent infection and fluid loss, and promote the natural healing process. In this proposal, we develop the use of noninvasive ultrasound fields to accelerate tissue repair.