The potential of physiologically relevant in vitro cell culture models for studying physiological and pathophysiological phenomena has been widely recognized as replacements for animal and conventional in vitro models. To create models that accurately replicate the structure and function of tissues and organs, it is essential to comprehend the biophysical and mechanical features of the extracellular matrix (ECM) and incorporate them into the in vitro cell culture models. Therefore, we first aimed to investigate how nanotopography can modulate cell behaviors by studying cell behaviors on nanostructures of various aspect ratios on a cobalt-chromium-molybdenum (CoCrMo) alloy surface. We also explored the impact of nanofibrous membranes on the formation of alveolar epithelium, which is critical for lung alveolar interstitium chips. In addition, we investigated the effect of mechanical stretch on cell behaviors and focused on how the dimensionality of the stretch affects cell behaviors. To create physiologically relevant in vitro models based on our findings, we engineered a stem cell niche using a combination of nanofibrous membranes, mechanical stretch, and a soft substrate, and evaluated its impact on stem cell behaviors. Finally, we created a biomimetic human lung interstitium chip for application in physiological and pathophysiological in vitro studies.

The heart is a dynamic environment that is constantly experiencing some degree of remodeling from the point of development, all the way through adulthood. While many genetic components may contribute to the overall presentation of hypertrophic cardiomyopathy (HCM), mutations occurring in sarcomere components such as myosin binding protein C3 (MYBPC3) are of the greatest popularity for study. Aiming to understand the mechanisms underlying heart diseases and to develop effective treatments that circumvent the need for direct patient study, we investigated the use of a platform to mimic the unique physiological conditions of HCM within an in-vitro setting. Following the induction of mechanical stretch on three human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) cell lines containing mutations for MYBPC3 (WT, HET, HOM), all displayed HCM like reactions in calcium waveform. In conclusion, this system demonstrated the potential to apply a constant, static strain to healthy and mutated hiPSC-CMs for the MYBPC3 protein to model HCM in-vitro.