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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB008996-05
Application #
8309357
Study Section
Special Emphasis Panel (ZEB1-OSR-B (O1))
Program Officer
Lopez, Hector
Project Start
2008-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$489,931
Indirect Cost
$171,794
Name
University of Rochester
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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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