Abstract
We describe a microfiber-shaped hepatic tissue for in vitro macroscopic tissue assembly, fabricated using a double coaxial microfluidic device and composed of cocultured Hep-G2 cells and human umbilical vein endothelial cells (HUVECs). The appropriate coculture conditions for Hep-G2 cells and HUVECs in the microfiber-shaped tissue were optimized by changing the thickness of the core and the cell ratio. The HUVEC networks were formed in the microfiber-shaped tissue following culture for 3 days. Using this microfiber-shaped tissue as a building block, two types of macroscopic assembled tissues were constructed—parallel and reeled tissues. In both tissue types, the connection of the HUVEC network across the adjacent microfiber-shaped tissues was established after 2 days, because the calcium alginate shell of the microfiber-shaped tissue was enzymatically removed. Our approach could facilitate the generation of complex and heterogeneous macroscopic tissues mimicking the major organs including the liver, kidney, and heart for the treatment of critically ill patients.
Highlights
Concomitant with technological development in regenerative medicine, research focus on technologies to reconstruct in vitro threedimensional (3D) tissues has been increasing considerably in recent years
As for the cell composition of the building blocks, microfibershaped tissues in the core-shell hydrogel microfibers have been formed by using a single cell type
Microfibers containing multiple types of cells have been reported; for example, glial cells and neurons differentiated from neural stem cells17,20 and musclelike cells differentiated from dedifferentiated fat cells
Summary
Concomitant with technological development in regenerative medicine, research focus on technologies to reconstruct in vitro threedimensional (3D) tissues has been increasing considerably in recent years. One of the goals of regenerative medicine is to produce functional macroscopic tissues by combining these scaffolds with a wide variety of cells derived from stem cells, including induced pluripotent stem cells (iPSCs).. One of the goals of regenerative medicine is to produce functional macroscopic tissues by combining these scaffolds with a wide variety of cells derived from stem cells, including induced pluripotent stem cells (iPSCs).3 To construct such functional macroscopic tissues in vitro, tissue engineering technologies that can assemble complicated and ordered structures composed of multiple types of cells are necessary. With regard to the generation of complex tissues containing multiple cell types, it is difficult to design and fabricate the detailed structures of such tissues using this top-down tissue engineering approach To overcome this difficulty, the focus has recently shifted toward a bottom-up approach to reconstruct complex functional tissues in vitro..
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