Incurable breast cancer bone metastasis causes widespread bone loss,
resulting in fragility, pain, increased fracture risk, and ultimately
increased patient mortality. Increased mechanical signals in the
skeleton are anabolic and protect against bone loss, and they may also
do so during osteolytic bone metastasis. Skeletal mechanical signals
include interdependent tissue deformations and interstitial fluid flow,
but how metastatic tumor cells respond to each of these individual
signals remains under-investigated, a barrier to translation to the
clinic. To delineate their respective roles, we report computed
estimates of the internal mechanical field of a bone-mimetic scaffold
undergoing combinations of high and low compression and perfusion using
multiphysics simulations. Simulations were conducted in advance of
multi-modal loading bioreactor experiments with bone metastatic breast
cancer cells to ensure that mechanical stimuli occurring internally were
physiological and anabolic. Our results show that mechanical stimuli
throughout the scaffold were within the anabolic range of bone cells in
all loading configurations, were homogenously distributed throughout,
and that combined high magnitude compression and perfusion synergized to
produce the largest wall shear stresses within the scaffold. These
simulations, when combined with experiments, will shed light on how
increased mechanical loading in the skeleton may confer anti-tumorigenic
effects during metastasis.