Investigation of nanoscale topography and biomechanical tuning of PDMS substrates to enhance cardiomyocyte differentiation from human induced pluripotent stem cells

Abstract

PDMS (polydimethylsiloxane) is still the most widely used biomaterial for bioengineering studies, which can mimic the tissue stiffness and micro/nanostructure to improve the generation and investigation of human cardiomyocyte (iCM) differentiation from human induced pluripotent stem cells (hiPSCs). Hence, PDMS-based substrates modified to reflect biomechanical—stiffness-related—and biophysical—topography-related—properties, in combination with biochemical cues, can enhance the efficiency of in vitro iCM generation. In this study, human fetal cardiomyocytes (HFCMs) were isolated and their natural geometrical micro/nanotopography was imprinted on PDMS surfaces with different stiffnesses combined with tailored biochemical factors, and the impact of the three factors on the differentiation of hiPSC-derived CM (iCM) was evaluated. The results show that the combination of biophysical, biomechanical, and biochemical factors could improve the expression of iCM differentiation and maturation markers compared to biochemical factors alone. Based on these findings, which can be applied in organ-on-chip studies, by imitating the in vivo environment, cultured cells behave authentically, providing realistic platforms for studying biological systems and ensuring accurate, translatable results.