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1 Departments of Biomedical Engineering and Mechanical & Aerospace Engineering, Case Western Reserve University, Cleveland, OH, USA; Orthopedic Research Center, The Cleveland Clinic Foundation, Cleveland, OH, USA
2 Department of Applied Biology and Biomedical Engineering, Rose-Hulman Institute of Technology, Terre Haute, IN, USA
* To whom correspondence should be addressed. E-mail: knothetate{at}case.edu.
Bone physiology is a subject that can be examined on multiple scales. Results of cellular-level studies, typically in vitro, are often extrapolated to attempt to understand tissue and organ physiology. Results of organ- or organism-level studies are often analyzed to attempt to deduce the state(s) of the cells within the larger system(s). Although phenomena on all of these scales - cell, tissue, organ, system, organism - are interlinked and contribute to the overall health and function of bone tissue, it is difficult to relate research between these scales. For example, groups of cells in an exogenous, in vitro environment that is well-defined by the researcher would not be expected to function similarly to those in a dynamic, endogenous environment, dictated by systemic as well as organismal physiology. This review of the literature on bone cell culture describes potential causes and components of cell "culture shock" - behavioral variations associated with the transition from in vivo to in vitro environment - focusing on investigations of mechanotransduction and experimental attempts to mimic aspects of bone tissue on a macroscopic scale. The state of the art is reviewed and new approaches are suggested to begin bridging the gap between two-dimensional cell cultures in petri dishes and the three-dimensional environment of living bone tissue.
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