title: A 3D bioprinting system to produce human-scale tissue constructs with structural integrity.
abstract: A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 μm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Kang
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
authors.forename: Sang Jin
authors.identifier: http://orcid.org/0000-0002-3899-1909
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
authors.forename: In Kap
authors.initials: IK
authors.lastname: Ko
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Kengla
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D062028:Bioprinting / Q000379:methods*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008334:Mandible / Q000502:physiology; D011108:Polymers / Q000737:chemistry; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011108:Polymers