title: Tissue engineering by self-assembly of cells printed into topologically defined structures.
abstract: Understanding the principles of biological self-assembly is indispensable for developing efficient strategies to build living tissues and organs. We exploit the self-organizing capacity of cells and tissues to construct functional living structures of prescribed shape. In our technology, multicellular spheroids (bio-ink particles) are placed into biocompatible environment (bio-paper) by the use of a three-dimensional delivery device (bio-printer). Our approach mimics early morphogenesis and is based on the realization that the genetic control of developmental patterning through self-assembly involves physical mechanisms. Three-dimensional tissue structures are formed through the postprinting fusion of the bio-ink particles, in analogy with early structure-forming processes in the embryo that utilize the apparent liquid-like behavior of tissues composed of motile and adhesive cells. We modeled the process of self-assembly by fusion of bio-ink particles, and employed this novel technology to print extended cellular structures of various shapes. Functionality was tested on cardiac constructs built from embryonic cardiac and endothelial cells. The postprinting self-assembly of bio-ink particles resulted in synchronously beating solid tissue blocks, showing signs of early vascularization, with the endothelial cells organized into vessel-like conduits.
authors.affiliation: Department of Physics, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Karoly
authors.initials: K
authors.lastname: Jakab
authors.forename: Cyrille
authors.initials: C
authors.lastname: Norotte
authors.forename: Brook
authors.initials: B
authors.lastname: Damon
authors.forename: Francoise
authors.initials: F
authors.lastname: Marga
authors.forename: Adrian
authors.initials: A
authors.lastname: Neagu
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Besch-Williford
authors.forename: Anatoly
authors.initials: A
authors.lastname: Kachurin
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Church
authors.forename: Hyoungshin
authors.initials: H
authors.lastname: Park
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mironov
authors.forename: Roger
authors.initials: R
authors.lastname: Markwald
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
authors.forename: Gabor
authors.initials: G
authors.lastname: Forgacs
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D002645:Chickens; D004622:Embryo, Mammalian / Q000166:cytology; D006801:Humans; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology*; D018919:Neovascularization, Physiologic; D009940:Organoids; D051381:Rats; D018874:Spheroids, Cellular; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds