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  1. The bone is a mechanosensitive organ that is also a common metastatic site for prostate cancer. However, the mechanism by which the tumor interacts with the bone microenvironment to further promote disease progression remains to be fully understood. This is largely due to a lack of physiological yet user-friendly models that limit our ability to perform in-depth mechanistic studies. Here, we report a tunable bioreactor which facilitates the 3D culture of the osteocyte cell line, MLO-Y4, in a hydroxyapatite/tricalcium phosphate (HA/TCP) scaffold under constant fluidic shear stress and tunable hydrostatic pressure within physiological parameters. Increasing hydrostatic pressure was sufficient to induce a change in the expression of several bone remodeling genes such as Dmp1, Rankl, and Runx2. Furthermore, increased hydrostatic pressure induced the osteocytes to promote the differentiation of the murine macrophage cell line RAW264.7 toward osteoclast-like cells. These results demonstrate that the bioreactor recapitulates the mechanotransduction response of osteocytes to pressure including the measurement of their functional ability in a 3D environment. In conclusion, the bioreactor would be useful for exploring the mechanisms of osteocytes in bone health and disease. 
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  2. Abstract

    Synthetic biological systems are used for a myriad of applications, including tissue engineered constructs for in vivo use and microengineered devices for in vitro testing. Recent advances in engineering complex biological systems have been fueled by opportunities arising from the combination of bioinspired materials with biological and computational tools. Driven by the availability of large datasets in the “omics” era of biology, the design of the next generation of tissue equivalents will have to integrate information from single‐cell behavior to whole organ architecture. Herein, recent trends in combining multiscale processes to enable the design of the next generation of biomaterials are discussed. Any successful microprocessing pipeline must be able to integrate hierarchical sets of information to capture key aspects of functional tissue equivalents. Micro‐ and biofabrication techniques that facilitate hierarchical control as well as emerging polymer candidates used in these technologies are also reviewed.

     
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