Characteristics of in vitro osteoblastic cell loading models.

Normal loading strains of 200-2000 (mu)epsilon to bone result in bending forces, generating mechanical stretch and pressure gradients in canaliculi that drive extracellular fluid flow, resulting in stress on the membranes of osteocytes, lining cells, and osteoblasts. Under excess loading, as well as during unloading (e.g., microgravity, bed rest), the fluid shift and resultant change in interstitial fluid flow may play a larger role in bone remodeling than mechanical stretch. The in vitro model systems used to investigate mechanical loading of bone generate either fluid shear, hydrostatic compression, biaxial stretch, uniaxial stretch, or a combination of two or more of these forces. The results of in vitro experiments suggest that fluid shear is a major factor affecting bone cell metabolism. Both the flow-loop apparatus (which produces pulsatile flow and uses fluid shear as its principal stimulus) and the uniaxial silicone plate stretching apparatus (which generates cyclic stretch) create a reproducible and consistent stimulus. Endpoints measured in flow experiments, however, are short term and usually short lived, and it is unknown whether these changes impact the function of differentiated osteoblasts. Endpoints measured in uniaxial stretch experiments are generally long-term-sustained effects of mechanical perturbation and more easily relatable to changes in osteoblastic activity. Biaxial stretch devices create both bending and compressive forces, resulting in different types of force on the cells, with the relative amount of each depending on the position of the cell in the device. Therefore, systems that incorporate pulsatile fluid flow or uniaxial stretch as the principal stimulus should be further developed and implemented in the study of the relationship between mechanical loading and bone response.