Date of Award

Fall 12-16-2022

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Master of Science in Biomedical Engineering

Department

Biological Engineering

Advisor

Rosemary Smith

Second Committee Member

Scott Collins

Third Committee Member

Karissa Tilbury

Abstract

Neuromuscular development happens in a complex interconnected network of biochemical pathways. This complicated embryonic development follows a strong, functional, and precise neuromuscular network that has interested both scientists and engineers who seek to better understand neuromuscular diseases. These disorders can be inherited or acquired, and their severity and mortality can vary. Researchers first studied the neuromuscular network from an organismal perspective, and more recently from an embryological, cellular, molecular, biochemical, and genetic perspective. From these studies, the fundamental principles of motor neuron pathfinding to muscles are widely understood, but the molecular drivers of specific nerve-muscle pairing remain unknown. Although in vivo experiments provide a precise depiction of the living tissue environment, manipulating in vivo variables to recreate the neuromuscular development in the laboratory is difficult, and the results are frequently intricated by many uncertainties and unquantifiable variables which make it problematic to draw significant and relevant conclusions. In vitro experiments, on the other hand, provide a more controlled, precise, and repeatable motif, but they often lack biological realism. In this thesis, a novel in vitro, three-dimensional co-culture microfluidic system is presented that seeks to mimic parameters that influence the complex physiochemical and developmental environments found in vivo. This system enables the culture of embryonic stem cells in two adjacent chambers, where they are supplied with their individual, requisite media and morphogens to develop into two distinct types of tissues, either motor neurons or muscle fibers while enabling chemical communication through interconnecting microchannels. Experiments are underway to investigate the effects of skeletal muscles on differentiating motor neurons into specific motor neuron columnar identity and neuromuscular junction formation. Results are expected to increase our fundamental understanding of developmental processes, neural development, and neuromuscular junction formation in order to research and model degenerative diseases.

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