CELL FIBER TECHNOLOGY FOR ENGINEERING FUNCTIONAL 3D MODELS
Amy Hsiao1, Hiroaki Onoe1,2, Teru Okitsu1,3, Midori Negishi1,3, Shoji Takeuchi1,3,
1The University of Tokyo, Japan;
2Japan Science and Technology Agency, Japan;
3ERATO Takeuchi Biohybrid Innovation Project, Japan Science and Technology Agency
The proper functioning of many organs and tissues greatly depends on the structural organization of the constituent cells. In particular, tissues such as linear muscles, long nerve networks, and tubular blood vessels are better modeled by long, fibrous-shaped cellular constructs as they are often made up of cells that precisely align or extend in the longitudinal direction. Here, we use the cell fiber technology to fabricate and culture functional 3D fiber-shaped cellular constructs from various types of cells. Using a double co-axial microfluidic device, different types of cells suspended in natural extracellular matrix (ECM) proteins possessing an optimized stiffness can be encapsulated in meter-long core-shell hydrogel microfibers. By allowing the cells to migrate and connect with each other within the 3D micro-tubular space, we show that these fiber-shaped cellular constructs reconstitute intrinsic morphologies and functions of living tissues. We further applied this technology to encapsulate multipotent stem cells and differentiate the cells into functional tissues. To expand the versatility of 3D fiber-shaped cellular constructs as useful tissue engineering building blocks, we further demonstrate various assembling techniques such as reeling and weaving the constructs into macroscopic cellular structures. Finally, primary pancreatic islet cells encapsulated in the hydrogel microfibers and subsequently transplanted into diabetic mice normalized blood glucose concentrations for 2 weeks. These microfibers can be used as functional 3D models of fiber-shaped tissues such as muscle fibers, nerve networks, and blood vessels for drug testing, regenerative medicine, and tissue engineering of larger organs.