Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells

Area of Science:

• Biomaterials Science
• Neuroscience
• Tissue Engineering

Background:

• Direct-write bioprinting enables the creation of complex 3D tissue structures.
• Engineering functional neural tissue is crucial for in vitro modeling and regenerative medicine.

Purpose of the Study:

• To report the first instance of constructing neural tissue by printing human neural stem cells (hNSCs).
• To differentiate hNSCs in situ into functional neurons and supporting neuroglia within a 3D scaffold.

Main Methods:

• Utilized a novel, clinically relevant polysaccharide-based bioink (alginate, carboxymethyl-chitosan, agarose).
• Employed direct-write printing to encapsulate hNSCs within the bioink, forming a porous 3D scaffold.
• Facilitated in situ expansion and differentiation of encapsulated hNSCs.

Main Results:

• The bioink rapidly gelled via stable cross-linking, creating a supportive 3D scaffold.
• Differentiated neurons formed synaptic contacts and established functional networks.
• Neurons exhibited spontaneous activity and increased calcium response to bicuculline, expressing gamma-aminobutyric acid.

Conclusions:

• This bioprinting approach successfully engineers functional human neural tissue in vitro.
• The developed 3D neural tissues can advance research into human neural development, function, and disease.
• The method shows potential adaptability for engineering other 3D tissues using various stem cell types.