Date of Thesis

Spring 2026

Description

Introduction

Low-frequency, low-intensity ultrasound (LFLI US) has been shown to be a promising treatment for noninvasive accelerated chronic wound healing. However, the biological mechanisms of this ultrasound-assisted healing are not yet understood, limiting clinical adoption. The objective of this study is to characterize the effects of LFLI US on gene expression in a simulated chronic wound environment to gain a better understanding of the biological mechanisms underlying this therapeutic.

Methods

A simulated chronic wound environment consisting of endothelial cells and inflammatory M1 macrophages co-cultured in 3D was subject to LFLI US at 50, 100, or 150 mW/cm2 Spatial-Peak, Temporal-Peak (SPTP) intensity with a sham group subject to no US. The gene expression changes were quantified at time points of 4, 18, 24, and 48 hours post-exposure using RNA sequencing and compared for differentially expressed genes (DEGs), which were further analyzed through hierarchical clustering and a gene-level analysis.

Results and Discussion

Twelve genes were represented through seventy-nine DEGs (or genes that were differentially expressed across samples in comparing an US treatment group to another US treatment group of lower intensity or to sham). Of these twelve genes, many are involved in the JAK/STAT and MAPK pathways, which have been shown to be upregulated and overly active in chronic wounds. Through a gene-level analysis, these pathways were seen to be downregulated following US exposure, with the most prominent changes seen in genes encoding for chemokines at the 24-hour time point. The results suggest both a reduction and an increase in inflammation, supporting the initial hypothesis that inflammation may have to reach a certain threshold before macrophages can transition from the pro-inflammatory M1 to the pro-healing M2 phenotype. Similarly, results suggest both improved and reduced angiogenesis, prompting further investigation. Ultimately, this study suggests several pathways and chemokines that may play key roles in the mechanism by which LFLI US accelerates chronic wound healing.

Keywords

macrophages, endothelial cells, angiogenesis, RNA sequencing, gene expression, bioinformatics

Access Type

Honors Thesis

Degree Type

Bachelor of Science in Biomedical Engineering

Major

Biomedical Engineering

Minor, Emphasis, or Concentration

Mathematics

First Advisor

Olivia Boerman

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