(D-160) Conductive Electrospun Polymer Platforms Improve Stem Cell-Derived Cardiomyocyte Maturation

Introduction:: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) serve as potential platforms for disease modeling and high throughput drug screening. Though recent efforts have utilized electromechanical and paracrine stimulation to mature cardiomyocytes, appropriate electrical coupling in-vitro has yet to be achieved. Conductive polymers are attractive candidates to facilitate electrical maturation between gaps in hPSC-CM clusters or between diseased hPSC-CMs with conduction defects. Therefore, we hypothesize that a conductive polymer platform will better propagate electrical signals between hPSC-CMs and improve electrical maturation.


Materials and Methods:: Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) was blended with 8% w/v poly(vinyl alcohol) (PVA) to construct PEDOT:PSS/PVA conductive polymer scaffolds via electrospinning. hPSC-CMs were seeded on either conductive or non-conductive scaffolds and bulk RNA sequencing was performed to determine cardiac gene expression in the presence of PEDOT:PSS. hPSC-CMs were seeded in monolayer onto conductive substrates to determine the extent of desmoplakin localization, while sub-monolayer and monolayer densities were used to examine sarcomere organization and calcium handling abilities.

Results, Conclusions, and Discussions:: After performing bulk RNA sequencing on hPSC-CMs exposed to either 8% PVA or 9.75% PEDOT:PSS/PVA electrospun scaffolds, we found 287 differentially expressed genes (Fig. 1, a). Gene ontology (GO) terms (Fig. 1, b) associated with PVA-only scaffolds illustrate an increased stress response of hPSC-CMs on non-conductive scaffolds. In contrast, the presence of PEDOT:PSS leads to terms related to heart contraction and processes, thus suggesting increased cardiac gene expression on conductive scaffolds. Desmoplakin localization improved in the presence of PEDOT:PSS compared to an insulating scaffold, suggesting that a conductive environment is important in the mechanical coupling of hPSC-CMs. Sarcomere organization scaled with increasing PEDOT:PSS concentration at both sub-monolayer and monolayer densities, suggesting that scaffold conductivity can improve cytoskeletal organization even in the absence of a monolayer. Moreover, the presence of PEDOT:PSS induced higher calcium flux with shorter time to peak in a dose-dependent manner, which also suggests that calcium handling improves with increasing scaffold conduction.

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