title: Laser printing of three-dimensional multicellular arrays for studies of cell-cell and cell-environment interactions.
abstract: Utilization of living cells for therapies in regenerative medicine requires a fundamental understanding of the interactions between different cells and their environment. Moreover, common models based on adherent two-dimensional cultures are not appropriate to simulate the complex interactions that occur in a three-dimensional (3D) cell-microenvironment in vivo. In this study, we present a computer-aided method for the printing of multiple cell types in a 3D array using laser-assisted bioprinting. By printing spots of human adipose-derived stem cells (ASCs) and endothelial colony-forming cells (ECFCs), we demonstrate that (i) these cell spots can be arranged layer-by-layer in a 3D array; (ii) any cell-cell ratio, cell quantity, cell-type combination, and spot spacing can be realized within this array; and (iii) the height of the 3D array is freely scalable. As a proof of concept, we printed separate spots of ASCs and ECFCs within a 3D array and observed cell-cell interactions in vascular endothelial growth factor-free medium. It has been demonstrated that direct cell-cell contacts trigger the development of stable vascular-like networks. This method can be applied to study complex and dynamic relationships between cells and their local environment.
authors.affiliation: Department of Nanotechnology, Laser Zentrum Hannover e. V., Hannover, Germany. m.gruene@lzh.de
authors.forename: Martin
authors.initials: M
authors.lastname: Gruene
authors.forename: Michael
authors.initials: M
authors.lastname: Pflaum
authors.forename: Christian
authors.initials: C
authors.lastname: Hess
authors.forename: Stefanos
authors.initials: S
authors.lastname: Diamantouros
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schlie
authors.forename: Andrea
authors.initials: A
authors.lastname: Deiwick
authors.forename: Lothar
authors.initials: L
authors.lastname: Koch
authors.forename: Mathias
authors.initials: M
authors.lastname: Wilhelmi
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhoevel
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Boris
authors.initials: B
authors.lastname: Chichkov
mesh_terms: D000818:Animals; D002417:Cattle; D002450:Cell Communication / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007834:Lasers; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic / Q000187:drug effects; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A