BME PhD Defense Announcement for Zachary Davis (D. Chan, advisor)

Everyone is invited to attend the public presentation beginning at 11:00 AM.

Title: Understanding Extracellular Matrix Characteristics in Bone and Tissue-Engineered Repair Scaffolds Using Pre-Clinical Imaging Techniques

Date: October 3^rd, 2025

Time: 11:00 AM

Location: ABE 1164

Committee: (Chair) Deva Chan, Julie Liu, Craig Goergen, Chad Carroll

Abstract

This thesis highlights the importance of hyaluronan in bone remodeling and evaluates tissue-engineered constructs using pre-clinical imaging techniques. The first part of the thesis investigates the effects of the hyaluronan synthase genes using genetic knockout mice (Has1^-/- and Has3^-/-) to determine their effects on trabecular bone morphometry as well as whole bone mechanics. Previous studies did not account for the weight differences that are present within the mice due to the genetic knockout; thus, Chapter 2 fills in that gap. We show that even when accounting for body weight, trabecular bone morphometry and femoral whole bone mechanics still differ. One key aspect of this work is that the genetic knockout mice also exhibit sex-based differences, with certain genetic knockouts affecting females more significantly than males. The next part of the thesis involves examining hyaluronan from a different perspective, within tissue-engineered hydrogels. The goal of that study was to determine if quantitative magnetic resonance imaging (qMRI) can detect scaffold content changes driven by altering hyaluronic acid concentration and molecular weight within collagen hydrogels. This study showed that unmodified hyaluronic acid at low concentrations does not significantly impact qMRI outputs, nor could qMRI be used as a significant predictive model for hyaluronic acid concentration general linear model (GLM) analysis. Building on this work, collagen hydrogels without hyaluronic acid were then studied. Using similar qMRI techniques and GLM analysis, we found that T₂ and T₂* were the most significant predictors of collagen in these gels. We also created two significant collagen models containing qMRI metrics. Together, the studies in this thesis demonstrate the importance of ECM components in both bone integrity and architecture, as well as the utility of non-invasive imaging techniques in evaluating repair constructs in clinical settings.