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Biotechnol Bioeng. 2018 Apr;115(4):1076-1085. doi: 10.1002/bit.26524. Epub 2018 Jan 19.

Perfusion applied to a 3D model of bone metastasis results in uniformly dispersed mechanical stimuli.

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Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, Massachusetts.
Department of Biology, University of Massachusetts, Amherst, Massachusetts.
Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts.


Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical cues in the skeleton are an important microenvironmental parameter that modulate tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. We focused on interstitial fluid flow based on its well-known role in bone remodeling and in primary breast cancer. We created a full-scale, microCT-based computational model of a 3D model of bone metastasis undergoing applied perfusion to predict the internal mechanical environment during in vitro experimentation. Applied perfusion resulted in uniformly dispersed, heterogeneous fluid velocities, and wall shear stresses throughout the scaffold's interior. The distributions of fluid velocity and wall shear stress did not change within model sub-domains of varying diameter and location. Additionally, the magnitude of these stimuli is within the range of anabolic mechanical signals in the skeleton, verifying that our 3D model reflects previous in vivo studies using anabolic mechanical loading in the context of bone metastasis. Our results indicate that local populations of cells throughout the scaffold would experience similar mechanical microenvironments.


CFD; bone; metastasis; perfusion; scaffold; tissue engineering


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