3D Liver-Specific Synthetic Scaffold Systems for Hepatocyte Differentiation and Disease Modeling

End-stage liver failure is a devastating disorder and currently the only effective treatment is liver transplantation (1). As there is a shortage of suitable liver donors, many patients die while waiting for liver transplantation (2). Tissue engineering is a step toward alleviating the need for donor organs (3). While the development of fully functional bioartificial organs is a long-term goal, a shorter term application tissue engineering technologies is the ability to develop improved 3D cell culture and scaffolding technologies that both better recapitulate the natural environment of the liver and lead to improved cell functionality. Maintenance of hepatocytes in traditional primary culture remains extremely challenging due to their short life span in vitro and rapid loss of hepatic function under industry-standard, 2D in vitro sandwich cell culture conditions (4). Stem and progenitor cells, especially induced pluripotent stem (iPS) cells, are a new alternative to primary cells but often have decreased functionality. Our preliminary results show that a small 3D bioscaffold culture system leads to increased hepatocyte functionality in both primary and iPS-derived hepatocytes. Through the NU-NTU Nanomedicine Institute collaboration, we propose to develop a 3D nanofibrous scaffold that mimics the native liver extracellular matrix (ECM) both at the physical as well as chemical aspects for differentiation of iPS cells toward a mature hepatocyte-like phenotype. This collaboration combines technologies developed in the Wertheim Lab (NU) and Tan Lab (NTU) and utilizes a therapeutic liposomal delivery system from the Mirkin Lab (NU). Dr. LP Tan (NTU) was trained as a polymer physics engineer and has been working on biopolymeric materials for tissue engineering applications over the past decade. Dr. Jason Wertheim (NU) is a practicing transplant surgeon with a PhD in Bioengineering. His research is in organ/tissue engineering with an active, NIH funded laboratory studying