The liver is one of the largest organs in our bodies and performs a multitude of functions such as, metabolism, detoxification, and plays a major role in the body's complex defense mechanisms. The deterioration in any one of the liver's functions can cause serious, life-threatening health problems. The design of tissue-engineered livers and liver-support devices can be accelerated if model hepatic units are available to systematically test their response to a range of stimuli. There is currently no generally applicable methodology to design hepatic culture systems where primary hepatocytes and liver sinusoidal endothelial cells (two of the major cell types found in the liver) are arranged in a stratified structure. We have assembled three-dimensional (3-D) cellular architectures comprised of primary hepatocytes and liver sinusoidal endothelial cells (LSECs) that mimic in several aspects the hepatic structure in vivo. The liver-mimetic architectures are comprised of primary hepatocytes, an intermediate nano-scale biocompatible and biodegradable polyelectrolyte (PE) scaffold and LSECs. Hepatocyte phenotypic function and detoxification profiles are being investigated using these 3D models.