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.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZEB1-OSR-B (O1))
Program Officer
Lopez, Hector
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Rochester
Biomedical Engineering
Schools of Engineering
United States
Zip Code
Sevilla, Carlos A; Dalecki, Diane; Hocking, Denise C (2013) Regional fibronectin and collagen fibril co-assembly directs cell proliferation and microtissue morphology. PLoS One 8:e77316
Garvin, Kelley A; VanderBurgh, Jacob; Hocking, Denise C et al. (2013) Controlling collagen fiber microstructure in three-dimensional hydrogels using ultrasound. J Acoust Soc Am 134:1491-502
Roy, Daniel C; Mooney, Nancie A; Raeman, Carol H et al. (2013) Fibronectin matrix mimetics promote full-thickness wound repair in diabetic mice. Tissue Eng Part A 19:2517-26
Roy, Daniel C; Wilke-Mounts, Susan J; Hocking, Denise C (2011) Chimeric fibronectin matrix mimetic as a functional growth- and migration-promoting adhesive substrate. Biomaterials 32:2077-87
Garvin, Kelley A; Dalecki, Diane; Hocking, Denise C (2011) Vascularization of three-dimensional collagen hydrogels using ultrasound standing wave fields. Ultrasound Med Biol 37:1853-64
Garvin, Kelley A; Hocking, Denise C; Dalecki, Diane (2010) Controlling the spatial organization of cells and extracellular matrix proteins in engineered tissues using ultrasound standing wave fields. Ultrasound Med Biol 36:1919-32