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 (Corresponding Author), Ali Khademhosseini (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

8 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 languageEnglish
Pages (from-to)13293-13303
Number of pages11
JournalACS applied materials & interfaces
Volume10
Issue number16
DOIs
Publication statusPublished - 25 Apr 2018

Fingerprint

Bioreactors
Screening
Hydrogels
Stem cells
Hydrogel
Gelatin
Compaction
Biocompatible Materials
Stiffness matrix
Biomaterials
Tissue
Chemical analysis

Keywords

  • UT-Hybrid-D
  • Dynamic compression bioreactor
  • High-throughput screening
  • Human mesenchymal stem cells
  • Mechanical stimulation
  • 3D mechanobiology

Cite this

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 & interfaces. 2018 ; Vol. 10, No. 16. pp. 13293-13303.
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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.",
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Seo, J, Shin, JY, Leijten, J, Jeon, O, Bal Öztürk, A, Rouwkema, J, Li, Y, Shin, SR, Hajiali, H, Alsberg, E & Khademhosseini, A 2018, 'Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions' ACS applied materials & interfaces, vol. 10, no. 16, pp. 13293-13303. https://doi.org/10.1021/acsami.7b17991

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 (Corresponding Author); Khademhosseini, Ali (Corresponding Author).

In: ACS applied materials & interfaces, Vol. 10, No. 16, 25.04.2018, p. 13293-13303.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Seo, Jungmok

AU - Shin, Jung Youn

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AU - Bal Öztürk, Ayça

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AU - Li, Yuancheng

AU - Shin, Su Ryon

AU - Hajiali, Hadi

AU - Alsberg, Eben

AU - Khademhosseini, Ali

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