Development of simple 3D-printed scaffolds for liver tissue engineering

Abstract

One solution to the increasing need for liver transplants is to grow implantable liver tissue in the lab. A tissue-engineered liver for transplantation will require complex structures to support cell differentiation and integration with surrounding vasculature. Recent developments in 3D-printing (3DP™) technology allow the construction of such geometrically complex scaffolds out of biodegradable polymers. These artificial tissues should maintain healthy, functional hepatocytes in proper contact with supporting cell types in the context of proper flow cues. This project comprises three major efforts. First, the design and development of a 3D-printed scaffold, constructed of a porous biodegradable polymer matrix, for flow bioreactor culture. Second, the development of protocols for the production, preparation, and flow support of these scaffolds. And third, the employment of standard cell culture methodologies to test the ability of these scaffolds to support liver tissue cultures. Initial cell culture experiments showed similar rates of albumin production in the polymer disk scaffolds compared to cells in silicon-chip scaffolds under appropriately scaled flow conditions, indicating that the polymer scaffolds maintain functioning liver tissue. Further, histology sections of liver tissue grown on these polymer scaffolds show organization of cells into structures reminiscent of in vivo liver. The results of this study show that 3D-printed porous polymer scaffolds have great potential for use as biodegradable tissue culture support devices. It is believed that, combined with printing technologies now under development, the technologies developed in this thesis will help facilitate the construction of an implantable tissue engineered liver.