Multifunctional Printed Scaffolds for Enhancing Hepatocyte Viability and Function

The proposed research aims to use multifunctional 3D bioprinted scaffolds incorporating bioactive agents such peptide nanostructures and support cells to enhance the viability and function of hepatocytes for liver tissue engineering. The lack of liver donors for patients with end stage liver disease (ESLD) is a major healthcare obstacle. Developing organ replacements or functional liver units using tissue engineering strategies as an alternative treatment is a promising possibility to alleviate this significant need. The interplay between microenvironmental cues and cell behavior in liver tissue engineering, however, is still not well understood. This research hopes to establish and understand trends in 3D scaffold design and bioactive agent delivery to start to identify key components in the microenvironment that can enhance liver cell function and normal liver tissue formation both in vitro and in vivo. The hypothesis is that the viability and function of hepatocytes can be significantly enhanced by: 1) optimizing scaffold architecture, which can alter hepatocyte aggregation and cellcell contact; 2) including functional moieties for growth factor delivery via selfassembling peptide amphiphile (PA) nanofibers; and 3) coculturing stromal cells and hepatocytes with 3D spatial control. Small “liver units” will be created using 3D bioplotted scaffolds of varying pore size and geometry, peptidebased nanostructures and growth factors for bioactive signaling, and liver cells (primary hepatocytes, induced pluripotent stem cellderived hepatocytes, and stromal cells) that are spatially patterned in 3D to change microenvironmental cues and determine what conditions promote optimal hepatocyte viability and function. Materials characterization, in vitro evaluation of viability, proliferation, and function, as well as in vivo assessment of angiogenesis, scaffold degradation, and tissue synthesis will be performed to evaluate the potential of these multifunctional scaffolds for liver tissue engineering. The results from this research will provide the necessary preliminary data for securing R01 funding that will help establish Dr. Shah as an independent investigator in the liver tissue engineering field.