Journal
ADVANCED HEALTHCARE MATERIALS
Volume 5, Issue 12, Pages 1429-1438Publisher
WILEY
DOI: 10.1002/adhm.201600095
Keywords
3D bioprinting; 3D human neural tissue; cell encapsulation; human stem cells; polysaccharide bioink
Funding
- Australian Research Council (ARC) Centre of Excellence Scheme [CE140100012]
- Australian National Fabrication Facility (ANFF)-Materials Node
- ARC through an ARC Laureate Fellowship [FL110100196]
- Consejo Nacional de Ciencia y Tecnologia (CONACYT, Mexico)
- National Basic Research Program of China [2012CBA01300]
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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.
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