Author ORCID Identifier

https://orcid.org/0009-0005-6605-4938

Date of Award

2026

Document Type

Thesis (Master's)

Department or Program

Engineering Sciences

First Advisor

John X. Zhang, Ph. D.

Second Advisor

Katherine R. Hixon, Ph. D.

Third Advisor

Jifeng Liu, Ph. D.

Abstract

Adult cardiomyocytes (CMs) are among the most challenging cells to culture in vitro, given their poor adherence to plastic culture wells and poor maturation outside the native extracellular matrix (Narkar et al., 2022). Human induced pluripotent stem cell-derived CMs (hiPSC-CMs) offer a viable alternative to study heart development and disease progression. While not comparable to adult CMs in their maturity (Narkar et al., 2022), they mimic the clinical phenotypes of heart failure and are more feasible to culture. Nevertheless, hiPSC-CMs require specialized culture conditions that cannot be achieved with 2D static culturing, which fail to replicate native tissue environments (X. Huang et al., 2022). Instead, microfluidic culturing may enhance the maturation profiles of hiPSC-CMs, given the ability to tune media flow rates to match cell shear stress values. Additionally, microfluidic culture may be 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 analyzed how dynamic media flow influences cells inside micropatterns, 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.

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