Building 3D human tissues in vitro for tissue- and organ on chip applications

Tissue and organ on chip (TOC) have been developed to permit the study of human physiology in a tissue-specific context, to enable development of novel in vitrodisease models, and to potentially serve as replacements of animals in drug development and toxics testing. For the TOC technology to meet the expectation to replace in part the animal model, it is mandatory to proceed towards the use of tissue and organs that correctly reproduce in composition and organization the extracellular space. Indeed, whilesophisticated microdevices have been designed, the engineered tissues still remain surrogates of the native counterparts. On this basis, we established a bottom-up tissue engineering strategy to build-up functional tissue in vitro. The basic idea driving our strategy is based on the concept that ECM is not a merely “passive” matrix holding cells and tissues in place, but it has a functional importance as dynamic repository for morphogens, cytokines and growth factors, which in vivoregulate diverse cellular processes [1]. Starting from this awareness we produced 3D tissue equivalent in which cells are embedded in their own ECM. We succeeded in obtaining a library of tissues and organs histologically and functionally competent and cultured them into opportunely designed microdevices under continuous flow and mechanical forces, thereby recreating key factors known to influence cell and tissues functions in vivo. Due to their somewhat unique properties such TOCs well mimic the organ-specific context, representing a biological environment that is much more effective at predicting human response than today’s cell cultures or animal testing.