Lets start with the advantages. When we grow cells the way most people do, by placing them in a dish and allowing them to attach we are growing cells in 2D. As you are aware few cells in the body grow in 2D, they actually grow in 3D. The idea behind 3D culture is to mimic the natural environment of the cell most closely making cell cultures more authentic in both structure and function. Cells growing in 2D have unlimited access to nutrients from the media above and the ability to remove waste products directly into the media. We also now know that cell-cell attachment and cell-matrix attachment are signal transducers and affect gene expression. As an example, Dr. Sangeeta Bhatia at M.I.T. has developed a system where rat hepatocyte cells are placed to mimic the natural organization of liver cells and has built a complete miniaturized ex vivo liver for drug metabolism studies (The Scientist May 1, 2013). Her approach is slightly different than 3D culture but it does point to the cell organization-funtion relationship. Others have shown how intestinal cells grown in 2D do not uptake blood pressure drugs because the bottom of the cells is where uptake occurs. In 2D cultures the bottom portion of the cell is not structurally relevant for uptake. In 3D culture uptake occurs.
On the downside, people have found some disadvantages to 3D culture but these disadvantages are being overcome by innovation. Some matrices are made from animal origin components which may make implementation for clinical work difficult. Some matrices made from tissue such as basement membrane extracts, can contain unknown or unwanted components like growth factors or viruses. Other matrices allow for attachment but not efficient removal of the cells making assay development difficult. To overcome these problems Gibco's AlgiMatrix 3D culture System are completely animal origin free. As the name implies, AlgiMatrix 3D is made from algae and once the cells are grown, the 3D matrix can be dissolved using a dissolving buffer, liberating the cells for assays or whatever is needed. Other approaches to minimize these potential problems have resulted in matrix-free 3D culture. N3DBIO's Bio-Assembler System actually levitates cells causing them to cluster together as groups making them have 3D contact without using a physical matrix. N3DBIO accomplishes this by providing a solution containing nanomagnetic particles that are incubated with the cells in culture. During a several hour incubation the magnetic particles are taken up by the cells. Once a supplied magnet is suspended above the wells the cells levitate together and grow as a cluster of cells in 3D.