Factors implicating the validity and interpretation of mechanobiology studies in simulated microgravity environments

Simulated microgravity (s‐μg) devices provide unique conditions for elucidating the effects of gravitational unloading on biological processes and are increasingly being applied for mechanobiology studies. However, without proper characterization of the mechanical environment generated by these systems, the interpretation of results is confounded and limited. Furthermore, the cell culture approaches central to s‐μg experimentation introduces new factors that can fundamentally affect results, but these are currently not addressed. It is essential to understand the complete culture environment and how constituent conditions can individually and synergistically affect cellular responses in order to correctly interpret results, otherwise outcomes may be misattributed to the effects of microgravity alone. For the benefit of the growing space biology community, this article critically reviews a typical s‐μg cell culture environment in terms of three key conditions: fluid‐mediated mechanical stimuli, oxygen tension and biochemical. These and the implications of other experimental variables for biological analysis are categorically discussed. A new set of controls is proposed to properly evaluate the respective effects of these conditions in s‐μg culture, along with a reporting matrix and potential strategies for addressing the current limitations of simulated microgravity devices as a platform for mechanobiology research.