Aspects of vascularization in Multi-Organ-Chips

Background Enormous efforts have been made to develop circulation systems for physiological nutrient supply and waste removal of in vitro cultured tissues. These developments are aiming for in vitro generation of organ equivalents such as liver, lymph nodes and lung or even multi-organ systems for substance testing, research on organ regeneration or transplant manufacturing. Initially technical perfusion systems based on membranes, hollow fibers or networks of micro-channels were used for these purposes. However, none of the currently available systems ensures long-term homeostasis of the respective tissue over months. This is caused by a lack of in vivo-like vasculature which leads to continuous accumulation of protein sediments and cell debris in the systems. Here, we demonstrate a closed and self-contained circulation system emulating the natural blood perfusion environment of vertebrates at tissue level.