Binary Colloidal Crystals Drive Spheroid Formation and Accelerate Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

• DOI: 10.1021/acsami.8b17090
• Publication Date: 2019-01-08T20:00:35Z
• Authors: Chang Cui; Jiaxian Wang; Duoduo Qian; Jiayi Huang; Jiao Lin; Peter Kingshott; Peng-Yuan Wang; Minglong Chen
• Keywords: Spheroid

The development of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provides significant advances to cell therapy, disease modeling, and drug screening applications. However, the current differentiation protocol is inefficient in mimicking biophysical biochemical characteristics cardiac niche. Hence, immature are often generated. In this study, hiPSC-CMs were generated on a new family substrates called monolayer binary colloidal crystals (BCCs). Four BCCs fabricated with different sizes (2 or 5 0.4 0.2 μm) materials [Si polystyrene (PS) poly(methyl methacrylate)] abbreviated as 2PS, 5PS, 2PM, 5PM. have complex surface micro-/nanotopographies heterogeneous chemistries which important modulators microenvironments vitro. results showed that hiPSCs formed adhered spheroids strong markers (Oct4, Nanog, Sox2) PM surfaces compared PS flat surfaces. After 30-day differentiation, markedly improved myofibril ultrastructures, Ca2+ handling, electrophysiological properties, indicating more mature 5PM similar adult heart tissue other terms genes (ACTC1, TNNT2, RYR2, SERCA2a, SCN5a, KCNJ2, CACNA1c, ITGB1, GJA1, MYH6, MYH7) protein (ssTnI cTnI) expressions. We further demonstrated facilitated cadherin switching (from E- N-) during N-cadherin expression, positively correlated cardiogensis (GATA4, MEF2c, NKX2.5). This study illuminated tailored nanotopography was beneficial hiPSC culture situ differentiation. one-step approach can be next-generation tool for expansion CM