High-fidelity computational fluid dynamics modeling to simulate perfusion through a bone-mimicking scaffold.

Breast cancer cells sense shear stresses in response to interstitial fluid flow in bone and induce specific biological responses. Computational fluid dynamics models have been instrumental in estimating these shear stresses to relate the cell mechanoresponse to exact mechanical signals, better informing experiment design. Most computational models greatly simplify the experimental and cell mechanical environments for ease of computation, but these simplifications may overlook complex cell-substrate mechanical interactions that significantly change shear stresses experienced by cells. In this paper, we construct a high-fidelity model, i.e., a digital twin, of a bone-mimicking scaffold experiencing fluid stresses from a custom perfusion bioreactor by creating a stabilized multi-domain finite element formulation that accounts for physical components of the bioreactor and true flow boundaries. Our goals include determination of a range of applied flow rates that result in physiological wall shear stresses, evaluation of wall shear stress sensitivity to scaffold fabrication, and validation of our bioreactor set-up for applying physiologically-relevant fluid stresses. This work will provide us with a more structured framework to study breast cancer mechanobiology in bone metastasis. Accurate shear stress estimations will allow us to understand how in vitro models of anabolic loading in bone affect the breast cancer cell mechanoresponse.