Hepatocellular engineering via acellular cadherin-derived microinterfaces

The development of cell-based therapies for liver failure relies on the availability of scaffolds that support high levels of cellular function. In this work, we functionalize biomaterial surfaces using a novel cell-based ligand as an alternative to traditional extracellular matrix-derived ligands. Initial studies in a model coculture system indicate that E-cadherin, a key cell-cell adhesion molecule present on hepatocytes, enhances liver-specific function when presented by chaperone cells. We then investigate the behavior of hepatocytes on acellular cadherin-presenting immobilized microparticle-based biomaterials. Biological activity of acellular cadherins is ensured by appending to the extracellular domain of E-cadherin an immunoglobulin Fc region, which induces dimerization and specifically adheres to a Protein A coating on the microbeads. Hepatocellular function was elevated on these surfaces as compared to the control, Fc presenting surfaces. Both surfaces exhibited similar cell adhesion and morphogenesis, suggesting that induction of hepatocyte function by cadherins was due to signaling activities rather than adhesive activities. Overall, we have demonstrated that functionalization of biomaterials with acellular cadherins is a powerful way to induce hepatocyte function.