title: Hybrid hydrogel-aligned carbon nanotube scaffolds to enhance cardiac differentiation of embryoid bodies.
abstract: Carbon nanotubes (CNTs) were aligned in gelatin methacryloyl (GelMA) hydrogels using dielectrophoresis approach. Mouse embryoid bodies (EBs) were cultured in the microwells fabricated on the aligned CNT-hydrogel scaffolds. The GelMA-dielectrophoretically aligned CNT hydrogels enhanced the cardiac differentiation of the EBs compared with the pure GelMA and GelMA-random CNT hydrogels. This result was confirmed by Troponin-T immunostaining, the expression of cardiac genes (i.e., Tnnt2, Nkx2-5, and Actc1), and beating analysis of the EBs. The effect on EB properties was significantly enhanced by applying an electrical pulse stimulation (frequency, 1Hz; voltage, 3V; duration, 10ms) to the EBs for two continuous days. Taken together, the fabricated hybrid hydrogel-aligned CNT scaffolds with tunable mechanical and electrical characteristics offer an efficient and controllable platform for electrically induced differentiation and stimulation of stem cells for potential tissue regeneration and cell therapy applications.
  
  
  CONCLUSIONS
  Dielectrophoresis approach was used to rapidly align carbon nanotubes (CNTs) in gelatin methacryloyl (GelMA) hydrogels resulting in hybrid GelMA-CNT hydrogels with tunable and anisotropic electrical and mechanical properties. The GelMA-aligned CNT hydrogels may be used to apply accurate and controllable electrical pulses to cell and tissue constructs and thereby regulating their behavior and function. In this work, it was demonstrated that the GelMA hydrogels containing the aligned CNTs had superior performance in cardiac differentiation of stem cells upon applying electrical stimulation in contrast with control gels. Due to broad use of electrical stimulation in tissue engineering and stem cell differentiation, it is envisioned that the GelMA-aligned CNT hydrogels would find wide applications in tissue regeneration and stem cell therapy.
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan.
authors.forename: Samad
authors.initials: S
authors.lastname: Ahadian
authors.affiliation: Graduate School of Environmental Studies, Tohoku University, Sendai 980-8579, Japan.
authors.forename: Shukuyo
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Nanobiotechnology for Diagnostics (Nb4D) Group, IQAC-CSIC, Jordi Girona 18-26, Barcelona 08034, Spain; CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Jordi Girona 18-26, Barcelona 08034, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ramón-Azcón
authors.affiliation: Advanced Ceramics Group, Materials Processing Unit, National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Estili
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Liang
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Graduate School of Environmental Studies, Tohoku University, Sendai 980-8579, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiku
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan; Department of Medicine, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; College of Animal Bioscience and Technology, Department of Bioindustrial Technologies, Konkuk University, Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea; Department of Physics, Faculty of Science, King Abdulaziz University, Jeddah 21569, Saudi Arabia. Electronic address: alik@rics.bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, Sendai 980-8577, Japan; Graduate School of Environmental Studies, Tohoku University, Sendai 980-8579, Japan. Electronic address: matsue@bioinfo.che.tohoku.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsue
mesh_terms: D000818:Animals; D016880:Anisotropy; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D004566:Electrodes; D058732:Embryoid Bodies / Q000166:cytology*; D005780:Gelatin / Q000737:chemistry; D006321:Heart / Q000254:growth & development*; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D018625:Microscopy, Atomic Force; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D020107:Troponin T / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D018076:DNA, Complementary; D020100:Hydrogels; D037742:Nanotubes, Carbon; D011108:Polymers; D020107:Troponin T; D005780:Gelatin
keywords: Carbon nanotubes; Cardiac differentiation; Electrical stimulation; Embryoid body; Hydrogel