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. 2021 Apr 28;9:645496. doi: 10.3389/fcell.2021.645496

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Copyright © 2021 Bessy, Itkin and Passaro.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Evolution of system complexity over time. Evolution in the organization complexity of engineered BM models with: (A) 2D co-cultures (feeder cells), (B) 3D co-culture within a hydrogel, (C) introduction of a source for medium renewal with either perfusion or the creation of a hollow tube, thus generating compartments within the tissue, (D) introduction of vasculature (self-assembled or engineered) bringing contact-dependent interaction in addition to compartmentalization, (E) introduction of a bone environment generating a segmented endosteal and vascular regions, with different ECM and cellular contents as well as different physical properties.