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.
Bibliographical noteFunding Information:
The authors gratefully acknowledge funding by the Defense Threat Reduction Agency under Space and Naval Warfare Systems Center Pacific contract no. N66001-13-C-2027. The authors also acknowledge funding from the National Institutes of Health (EB012597, AR057837, AR066193, DE021468, HL099073, and R56AI105024). Dr. Seo was partially supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2016R1A6A3A03006491) and KIST project (2E27930). Dr. Bal Ozturk was fully supported by post-doctoral research grant of The Scientific and Technological Research Council of Turkey (TUBITAK). J. L. acknowledges financial support from the Netherlands Organization for Scientific Research (NWO, Veni, #14328), the European Research Council (ERC, Starting Grant, #759425), and the Dutch Arthritis Foundation (#17-1-405).
Dr. Seo was partially supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2016R1A6A3A03006491) and KIST project (2E27930).
All Science Journal Classification (ASJC) codes
- Materials Science(all)