title: Layer-by-layer assembly of 3D tissue constructs with functionalized graphene.
abstract: Carbon-based nanomaterials have been considered as promising candidates to mimic certain structure and function of native extracellular matrix materials for tissue engineering. Significant progress has been made in fabricating carbon nanoparticle-incorporated cell culture substrates, but limited studies have been reported on the development of three-dimensional (3D) tissue constructs using these nanomaterials. Here, we present a novel approach to engineer 3D multi-layered constructs using layer-by-layer (LbL) assembly of cells separated with self-assembled graphene oxide (GO)-based thin films. The GO-based structures are shown to serve as cell adhesive sheets that effectively facilitate the formation of multi-layer cell constructs with interlayer connectivity. By controlling the amount of GO deposited in forming the thin films, the thickness of the multi-layer tissue constructs could be tuned with high cell viability. Specifically, this approach could be useful for creating dense and tightly connected cardiac tissues through the co-culture of cardiomyocytes and other cell types. In this work, we demonstrated the fabrication of stand-alone multi-layer cardiac tissues with strong spontaneous beating behavior and programmable pumping properties. Therefore, this LbL-based cell construct fabrication approach, utilizing GO thin films formed directly on cell surfaces, has great potential in engineering 3D tissue structures with improved organization, electrophysiological function, and mechanical integrity.
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Su Ryon
authors.initials: SR
authors.lastname: Shin
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Aghaei-Ghareh-Bolagh
authors.affiliation: Department of Chemistry & Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Ave. West, Waterloo, Ontario, N2L 3G1, Canada.
authors.forename: Xiguang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nikkhah
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sung Mi
authors.initials: SM
authors.lastname: Jung
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Dolatshahi-Pirouz
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Sang Bok
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Department of Mechanical Engineering, Inha University, Incheon, 402-751, Republic of Korea.
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Mehmet R
authors.initials: MR
authors.lastname: Dokmeci
authors.affiliation: Department of Chemistry & Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Ave. West, Waterloo, Ontario, N2L 3G1, Canada.
authors.forename: Xiaowu Shirley
authors.initials: XS
authors.lastname: Tang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
keywords: Cardiac tissue engineering; Graphene oxide; Poly L-lysine; Three-dimensional tissue construct; layer-by-layer