Bone remodeling platforms: Understanding the need for multicellular lab-on-a-chip systems and predictive agent-based models.

The purpose of this paper is to emphasize the need for more complex bone remodeling platforms that allow for investigations of intricate multicellular interactions that regulate this process. We discuss the efforts we have taken to develop lab-on-a-chip systems for bone remodeling and the motivation for pursuing more advanced multicellular models. Further, we discuss mathematical modeling opportunities that will allow experimental results to extend beyond the set laboratory conditions. We advocate for the development of an agent-based model comprised of multiple cellular automata of each bone cell type. In total, this work requires a combination of techniques from bone biology, microfluidics, cell mechanobiology, mechanics, and mathematical modeling. Thus, significant advancements within the field will require a collective contribution from a variety of research laboratories.