Defense Date

2009

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Anatomy & Neurobiology

First Advisor

Sheryl Finucane

Abstract

Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth factors. These paracrine factors affect other inflammatory cells, resident cells of the healing tissue, including fibroblasts and endothelial cells that are necessary for restoration of damaged tissue. The hypothesis of this investigation is that TUS enhances early healing, in part, through stimulation of macrophage release of paracrine factors involved in coordination of the cellular aspects of tissue healing and that specific levels of TUS are most stimulatory for macrophages. This study examined macrophage release of interleukin-1beta (IL-1Beta), vascular endothelial growth factor (VEGF), transforming growth factor-Beta 1 (TGF-B1) and fibroblast mitogens, in response to varied levels of TUS. Fibroblasts incubated up to 48-hours in media conditioned by TUS-stimulated macrophages were not induced to proliferate regardless of the parameters sets of TUS applied. TUS (1 MHz, 400mW/cm2 SATA, 20% duty cycle, 10-minute exposure) induced macrophage release of VEGF and IL-1Beta within 10-minutes post-TUS, without any additional release being stimulated at 1-hour post-insonation. No other combination of TUS parameters studied induced release of IL-1Beta and VEGF. TUS did not induce release of TGF-Beta 1 at either time point post-TUS. VEGF and IL-1Beta release occurred in conjunction with lactate dehydrogenase (LDH) release from treated macrophages, indicating non-specific cell membrane permeabilization was involved in the cellular response. For IL-1Beta, TUS-stimulated release was inhibited at lower exposure temperatures. Inhibition of TUS-induced release at lower temperatures indicates that a cellular metabolic process, most likely exocytosis, was also stimulated by TUS. Based on these results, it appears that TUS exposure at 1 MHz, 400mW/cm2 SATA, 20% duty cycle induces non-specific and cell-mediated release of secretory proteins. Thus, enhanced release of cytokines and growth factors from macrophages is a possible mechanism by which TUS enhances tissue healing.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2009

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