title: Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells.
abstract: Direct-write printing of stem cells within biomaterials presents an opportunity to engineer tissue for in vitro modeling and regenerative medicine. Here, a first example of constructing neural tissue by printing human neural stem cells that are differentiated in situ to functional neurons and supporting neuroglia is reported. The supporting biomaterial incorporates a novel clinically relevant polysaccharide-based bioink comprising alginate, carboxymethyl-chitosan, and agarose. The printed bioink rapidly gels by stable cross-linking to form a porous 3D scaffold encapsulating stem cells for in situ expansion and differentiation. Differentiated neurons form synaptic contacts, establish networks, are spontaneously active, show a bicuculline-induced increased calcium response, and are predominantly gamma-aminobutyric acid expressing. The 3D tissues will facilitate investigation of human neural development, function, and disease, and may be adaptable for engineering other 3D tissues from different stem cell types.
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.|State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Gu
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.|Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, 2522, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Tomaskovic-Crook
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Lozano
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.|Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, 3065, Australia.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kapsa
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Wallace
authors.affiliation: ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Squires Way, Fairy Meadow, New South Wales, 2519, Australia.|Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, 2522, Australia.|Department of Surgery, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, 3065, Australia.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Crook
mesh_terms: D001640:Bicuculline / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D066330:Printing, Three-Dimensional; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001640:Bicuculline
keywords: 3D bioprinting; 3D human neural tissue; cell encapsulation; human stem cells; polysaccharide bioink