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Multiphysics simulation of a compression - perfusion combined bioreactor to predict the mechanical microenvironment during bone metastatic breast cancer loading experiments
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  • Boyuan Liu,
  • Suyue Han,
  • Yahya Modarres-Sadeghi,
  • Maureen Lynch
Boyuan Liu
University of Massachusetts Amherst
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Suyue Han
University of Massachusetts Amherst
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Yahya Modarres-Sadeghi
University of Massachusetts Amherst
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Maureen Lynch
University of Colorado Boulder
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Abstract

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.

Peer review status:UNDER REVIEW

07 Aug 2020Submitted to Biotechnology and Bioengineering
08 Aug 2020Assigned to Editor
08 Aug 2020Submission Checks Completed
18 Aug 2020Reviewer(s) Assigned
27 Sep 2020Editorial Decision: Revise Major
27 Sep 2020Review(s) Completed, Editorial Evaluation Pending