Replication of the 3D architecture of tissues

Biological tissues are ensembles of various types of cells and extracellular molecules. Functionality in tissues arises from their components (cells and extracellular molecules) as well as from the location of those components relative to each other. The organization of the constituents of a tissue is known as histoarchitecture. As cell culture reaches beyond flat, rigid surfaces, several approaches have been published that attempt to re-create in vitro the three-dimensional (3D) histoarchitecture found in vivo. In these approaches, researchers use scaffolding molecules (extracellular matrix, ECM) of natural or synthetic origin to support cell growth1. Scaffolds harvested from tissues replicate precisely the in vivo ECM but they may be limited by its biologic variability2. Conversely, synthetic scaffolds3,4 provide tailored, defined, repeatable ECM but lack the chemical signaling completeness provided by biological scaffolds. Here we will review methods for replicating in vitro the 3D histoarchitecture of live tissues, focusing on those approaches that use (or are compatible with) tissue-harvested scaffolds.