Multiphysics simulation of a compression–perfusion combined bioreactor to predict the mechanical microenvironment during bone metastatic breast cancer loading experiments

• Published in: Biotechnology and bioengineering 2021-05, Vol.118 (5), p.1779-1792
• Main Authors: Liu, Boyuan, Han, Suyue, Modarres‐Sadeghi, Yahya, Lynch, Maureen E.
• Format: Article
• Language: English
• Subjects: Biomechanical Phenomena - physiology; Biomedical materials; Bioreactors; bone; Bone cancer; Bone loss; Bone Neoplasms - physiopathology; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - physiopathology; Compression; Computational fluid dynamics; Experiments; Female; Fluid flow; Fragility; Humans; Mechanical loading; Mechanical stimuli; Metastases; Metastasis; Microenvironments; multiphysics; Osteolysis; Pain; Perfusion; Scaffolds; Simulation; Skeleton; Stimuli; Stress concentration; Stress, Mechanical; tissue engineering; Tissue Engineering - methods; Tumor cells; Tumor Microenvironment - physiology; Wall shear stresses
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.27692

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 underinvestigated, 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 multimodal 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. Skeletal mechanical signals include interdependent tissue deformations and interstitial fluid flow. To delineate their respective roles on bone metastatic cells, the authors used multiphysics simulations to estimate strains/stresses within a bone‐mimetic scaffold during compression‐perfusion loading. They show that internal mechanical stimuli were homogenously distributed and within the skeleton's anabolic range, and that combined high magnitude compression‐perfusion produced the largest shear stresses. These simulations, when combined with experiments, will shed light on how increased loading may confer anti‐tumorigenic on bone metastasis.