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

Jungmok Seo; Jung Youn Shin; Jeroen Leijten; Oju Jeon; Ayça Bal Öztürk; Jeroen Rouwkema; Yuancheng Li; Su Ryon Shin; Hadi Hajiali; Eben Alsberg; Ali Khademhosseini

doi:10.1021/acsami.7b17991

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

Jungmok Seo, Jung Youn Shin, Jeroen Leijten, Oju Jeon, Ayça Bal Öztürk, Jeroen Rouwkema, Yuancheng Li, Su Ryon Shin, Hadi Hajiali, Eben Alsberg, Ali Khademhosseini

Department of Electrical and Electronic Engineering

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	13293-13303
Number of pages	11
Journal	ACS Applied Materials and Interfaces
Volume	10
Issue number	16
DOIs	https://doi.org/10.1021/acsami.7b17991
Publication status	Published - 2018 Apr 25

Bibliographical note

Funding 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).

Funding Information:
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).

Publisher Copyright:
© 2018 American Chemical Society.

All Science Journal Classification (ASJC) codes

Materials Science(all)

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Seo, J., Shin, J. Y., Leijten, J., Jeon, O., Bal Öztürk, A., Rouwkema, J., Li, Y., Shin, S. R., Hajiali, H., Alsberg, E., & Khademhosseini, A. (2018). Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions. ACS Applied Materials and Interfaces, 10(16), 13293-13303. https://doi.org/10.1021/acsami.7b17991

Seo, Jungmok ; Shin, Jung Youn ; Leijten, Jeroen ; Jeon, Oju ; Bal Öztürk, Ayça ; Rouwkema, Jeroen ; Li, Yuancheng ; Shin, Su Ryon ; Hajiali, Hadi ; Alsberg, Eben ; Khademhosseini, Ali. / Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions. In: ACS Applied Materials and Interfaces. 2018 ; Vol. 10, No. 16. pp. 13293-13303.

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title = "Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions",

abstract = "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.",

author = "Jungmok Seo and Shin, {Jung Youn} and Jeroen Leijten and Oju Jeon and {Bal {\"O}zt{\"u}rk}, Ay{\c c}a and Jeroen Rouwkema and Yuancheng Li and Shin, {Su Ryon} and Hadi Hajiali and Eben Alsberg and Ali Khademhosseini",

note = "Funding 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). Funding Information: 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). Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

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day = "25",

doi = "10.1021/acsami.7b17991",

language = "English",

volume = "10",

pages = "13293--13303",

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Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions. / Seo, Jungmok; Shin, Jung Youn; Leijten, Jeroen; Jeon, Oju; Bal Öztürk, Ayça; Rouwkema, Jeroen; Li, Yuancheng; Shin, Su Ryon; Hajiali, Hadi; Alsberg, Eben; Khademhosseini, Ali.

In: ACS Applied Materials and Interfaces, Vol. 10, No. 16, 25.04.2018, p. 13293-13303.

Research output: Contribution to journal › Article › peer-review

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T1 - Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions

AU - Seo, Jungmok

AU - Shin, Jung Youn

AU - Leijten, Jeroen

AU - Jeon, Oju

AU - Bal Öztürk, Ayça

AU - Rouwkema, Jeroen

AU - Li, Yuancheng

AU - Shin, Su Ryon

AU - Hajiali, Hadi

AU - Alsberg, Eben

AU - Khademhosseini, Ali

N1 - Funding 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). Funding Information: 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). Publisher Copyright: © 2018 American Chemical Society.

PY - 2018/4/25

Y1 - 2018/4/25

N2 - 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.

AB - 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.

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

Abstract

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