A novel poly-l-lactic acid scaffold that possesses a macroporous structure and a branching/joining three-dimensional flow channel network: its fabrication and application to perfusion culture of human hepatoma Hep G2 cells

In the development of large internal organ equivalents for use in humans, the organs themselves must be reorganized based on three-dimensional (3D) fabrication of biodegradable polymer scaffolds. To this end, appropriate design of the 3D structure—particularly with respect to the arrangement of a 3D flow channel network and macroporous structures for cell immobilization—is critical. In the present work, we therefore presented a new scaffold design based on a regular tetrahedron whose edge is 3.0 mm as a unit composing the entire shape and the 3D flow channel network of the scaffold. Such an advanced scaffold successfully fabricated through repeated layering/micromachining of macroporous PLLA/NH4HCO3 salt particle composite sheets followed by salt leaching and gas forming. This reliable production of a flow channel network over scaffolds is more promising than existing 3D microfabrication processes in which such networks are produced indirectly in the spaces remaining after fabrication. A preliminary short-term perfusion culture of Hep G2 cells demonstrated that, even in a small scaffold with a small volume of around 1.3 cm3, such a 3D flow channel arrangement is necessary to allow the cells to grow and function. Although the current dimensions of the design unit were not ideal, the basic design concept presented in this study shows great promise for use in the engineering of a large human organ equivalent.