3.15 Cell culture systems for studying biomaterial interactions with biological barriers

The human body has numerous physical barriers that prevent most harmful or foreign compounds from entering the body. These barriers are formed by unique cell types, which through their location-specific biological cell characteristics prevent compounds from passing between or through them or selectively allow only specific compounds to move across the barrier that they form. Multiple cell types are involved that together form the functioning barrier in a particular organ or tissue. In many cases, in vitro human multicellular culture systems have been developed. These in vitro cell culture models have been extremely valuable in determining the toxic effects of novel compounds on cellular functions and in studying the mechanisms of barrier formation, the uptake and localization of the compounds within the cell, as well as the effects on cell-cell interactions. Moreover, they represent a major hurdle for micro- and nanoparticle biomaterials designed for drug and gene delivery to the body. The purpose of this chapter is to present an overview of the important barriers in the body and to describe in detail specific in vitro coculture models of the upper and lower respiratory units of the lung, models of the human skin and models to study the blood-brain barrier. How these models mimic the natural tissue, what criteria are used to validate the models, and how these model systems can be applied to the study of novel biomaterials, especially in micro- and nanoparticulate form, are described.