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Abstract: Adult cardiomyocytes (CMs) are among the most challenging cells to culture in vitro, due to  poor adherence to plastic culture wells and poor maturation outside the native extracellular matrix. Human induced pluripotent stem cell-derived CMs (hiPSC-CMs) offer a viable cellular alternative to study early heart development and disease progression. While hiPSC-CMs are not comparable to adult CMs in their maturity, they mimic the clinical phenotypes of heart failure and are more feasible to culture in a lab environment. Nevertheless, hiPSC-CMs require specialized culture conditions that cannot be achieved with 2D static culturing, which fail to replicate the native tissue environments. Instead, microfluidic culturing may be used to enhance the maturation profiles of hiPSC-CMs, given the ability to tune media flow rates to match cell shear stress values. Additionally, microfluidic culture models may be significantly enhanced through substrate micropatterning, which directs specific cell attachment toward the desired mature cell profiles. While previous research has outlined the impact of microfluidic media flow and micropatterning on hiPSC-CM maturation, little work has been done to analyze how dynamic media flow influences cells inside micropatterns impacts cells, or how biomimetic-driven micropatterns can support maturation in combination with dynamic media flow. 

This work hypothesizes that dynamic flow combined with biomimetic-inspired micropatterns will improve hiPSC-CM maturation. Functional validation will include an analysis of cell morphology and gene expression compared to static culture. Through the intersection of advanced microfabrication and biological testing, this work will provide key insight into the impact of biomimetic culture on hiPSC-CM development, potentially establishing a new paradigm for cell culture.

Thesis Committee: John Zhang (chair), Professor Katie Hixon, Professor Jifeng Liu