Nia Myrie
BME PhD Defense Presentation

Date: 2026-02-26
Time: 2 - 4 pm ET
Location / Meeting Link: IBB Suddath Seminar Room 1128 / https://gatech.zoom.us/j/2503560220

Committee Members:
Andrés J. García, PhD (Advisor); Young C. Jang, PhD; Edward Botchwey, PhD; Stanislav Emelianov, PhD; Foteini Mourkioti, PhD


Title: Engineering a Synthetic Hydrogel for Muscle Stem Cell Delivery to the Dystrophic Diaphragm

Abstract:
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by the absence of dystrophin protein, which serves as structural support between the muscle fiber membrane and extracellular matrix (ECM). Without it, muscles undergo cycles of degeneration and regeneration. Overtime, DMD patients suffer from ambulatory disability and cardiorespiratory failure, the latter of which is a major contributor to premature death. Currently, treatment is primarily palliative and there is no cure. A treatment strategy is to transplant muscle satellite cells (MuSCs) to a target muscle to repopulate the stem cell niche and restore dystrophin to the muscle fibers. Challenges with this strategy include poor cell retention and survival upon transplantation. Delivering MuSCs to the diaphragm muscle, the primary respiratory muscle, poses additional challenges due to its thin morphology and deep-seated location. This project seeks to address these challenges by leveraging synthetic hydrogels as a vehicle for localized MuSC delivery to the diaphragm muscle. First, MuSCs were analyzed via flow cytometry to assess integrin expression and hydrogels were synthesized with adhesive ligands to support their proliferation, differentiation, and migration based on their integrin expression profile. Second, hydrogel-encapsulated MuSCs were delivered to the diaphragm of dystrophic mice, and the presence of engrafted cells and restored dystrophin was confirmed. Additionally, force testing and ultrasound imaging were used to characterize the elasticity and function of the diaphragm. Ultrasound imaging is particularly useful as we demonstrate the ability to evaluate the functionality and predict morphological features of the diaphragm muscle over time rather than at a single time point. Finally, dystrophic microtissues were generated in a four-pillar configuration for in vitro dystrophic diaphragm modelling and initial parameters for obtaining and maintaining microtissue yield were established. These results provide support for the therapeutic potential of stem cell delivery for DMD via synthetic hydrogels as well as an in vitro platform to supplement in vivo engraftment studies.