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ACS Appl Mater Interfaces. 2018 Apr 25;10(16):13293-13303. doi: 10.1021/acsami.7b17991. Epub 2018 Apr 13.

Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions.

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Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital , Harvard Medical School , Cambridge , Massachusetts 02139 , United States.
Harvard-MIT Division of Health Sciences and Technology , Massachusetts Institute of Technology , 77 Massachusetts Avenue , Cambridge , Massachusetts 02139 , United States.
Center for Biomaterials, Biomedical Research Institute , Korea Institute of Science and Technology , 14 Hwarang-ro , Seongbuk-gu, Seoul 02792 , Republic of Korea.
Department of Bioengineering, Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences , University of California-Los Angeles , Los Angeles , California 90095 , United States.
Department of Bioindustrial Technologies, College of Animal Bioscience and Technology , Konkuk University , Hwayang-dong , Gwangjin-gu, Seoul 143-701 , Republic of Korea.
Center of Nanotechnology, Department of Physics , King Abdulaziz University , Jeddah 21569 , Saudi Arabia.


Biophysical cues can potently direct a cell's or tissue's behavior. Cells interpret their biophysical surroundings, such as matrix stiffness or dynamic mechanical stimulation, through mechanotransduction. However, our understanding of the various aspects of mechanotransduction has been limited by the lack of proper analysis platforms capable of screening three-dimensional (3D) cellular behaviors in response to biophysical cues. Here, we developed a dynamic compression bioreactor to study the combinational effects of biomaterial composition and dynamic mechanical compression on cellular behavior in 3D hydrogels. The bioreactor contained multiple actuating posts that could apply cyclic compressive strains ranging from 0 to 42% to arrays of cell-encapsulated hydrogels. The bioreactor could be interconnected with other compressive bioreactors, which enabled the combinatorial screenings of 3D cellular behaviors simultaneously. As an application of the screening platform, cell spreading, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) were characterized in 3D gelatin methacryloyl (GelMA) hydrogels. Increasing hydrogel concentration from 5 to 10% restricted the cell spreading, however, dynamic compressive strain increased cell spreading. Osteogenic differentiation of hMSCs was also affected by dynamic compressive strains. hMSCs in 5% GelMA hydrogel were more sensitive to strains, and the 42% strain group showed a significant increase in osteogenic differentiation compared to other groups. The interconnectable dynamic compression bioreactor provides an efficient way to study the interactions of cells and their physical microenvironments in three dimensions.


3D mechanobiology; dynamic compression bioreactor; high-throughput screening; human mesenchymal stem cells; mechanical stimulation

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