Abstract
Human pluripotent stem cell-derived
cardiomyocytes (hPSC-CMs) are a promising cell source for cardiac regenerative
medicine and in vitro modeling. However, hPSC-CMs exhibit
immature structural and functional properties compared with adult
cardiomyocytes. Various electrical, mechanical, and biochemical cues have been
applied to enhance hPSC-CM maturation but with limited success. In this work,
we investigated the potential application of the semiconducting polymer
poly{[N,N′-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′-bithiophene)}
(P(NDI2OD-T2)) as a light-sensitive material to stimulate hPSC-CMs optically.
Our results indicated that P(NDI2OD-T2)-mediated photostimulation caused cell
damage at irradiances applied long-term above 36 μW/mm2 and did not regulate cardiac monolayer
beating (after maturation) at higher intensities applied in a transient
fashion. However, we discovered that the cells grown on P(NDI2OD-T2)-coated
substrates showed significantly enhanced expression of cardiomyocyte maturation
markers in the absence of a light exposure stimulus. A combination of
techniques, such as atomic force microscopy, scanning electron microscopy, and
quartz crystal microbalance with dissipation monitoring, which we applied to
investigate the interface of the cell with the n-type coating, revealed that
P(NDI2OD-T2) impacted the nanostructure, adsorption, and viscoelasticity of the
Matrigel coating used as a cell adhesion promoter matrix. This modified
cellular microenvironment promoted the expression of cardiomyocyte maturation
markers related to contraction, calcium handling, metabolism, and conduction.
Overall, our findings demonstrate that conjugated polymers such as P(NDI2OD-T2)
can be used as passive coatings to direct stem cell fate through interfacial
engineering of cell growth substrates.
Keywords
N-type organic semiconductor
light-sensitive materials
Biointerfacing applications
