Perfusion applied to a 3D model of bone metastasis results in uniformly dispersed mechanical stimuli. Issue 4 (19th January 2018)

• Record Type: Journal Article
• Authors: Liu, Boyuan; Han, Suyue; Hedrick, Brandon P.; Modarres‐Sadeghi, Yahya; Lynch, Maureen E.
• Is Part Of: Biotechnology and bioengineering. Volume 115:Issue 4(2018)
• Page Start: 1076
• Page End: 1085
• Publication Date: 2018-01-19
• Subjects: bone -- CFD -- metastasis -- perfusion -- scaffold -- tissue engineering; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.26524
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: 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. Abstract : Breast cancer cells preferentially metastasize to the skeleton and experience mechanical signals such as fluid flow. We created a full‐scale computational model of applied perfusion in a 3D model of bone metastasis to predict the mechanical environment during experimentation. Applied fluid flow resulted in heterogeneous fluid velocities and wall shear stresses that were evenly distributed through the scaffold, and their distributions persisted with varying sub‐domain diameter and location. These results indicate that local populations of cells throughout the scaffold experience similar mechanical microenvironments.