Dendrimer hydrazides as multivalent transient inter-cellular linkers

Deqiang Zhao; Siew Min Ong; Zhilian Yue; Zhiyong Jiang; Yi Chin Toh; Majad Khan; Jiahua Shi; Choon Hong Tan; J. Paul Chen; Hanry Yu

doi:10.1016/j.biomaterials.2008.05.019

Dendrimer hydrazides as multivalent transient inter-cellular linkers

Deqiang Zhao, Siew Min Ong, Zhilian Yue, Zhiyong Jiang, Yi Chin Toh, Majad Khan, Jiahua Shi, Choon Hong Tan, J. Paul Chen^*, Hanry Yu

^*Corresponding author for this work

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

24 Scopus citations

Abstract

Three-dimensional (3D) multi-cellular aggregates (MCAs), as a model scaffold-free tissue construct, are useful for engineering cell-dense and matrix-poor tissues for repair and regeneration applications. To facilitate rapid MCA formation with high degrees of linker consistency and performance, we synthesized a class of dendrimer hydrazides with 8, 16 and 32 arms that can react with the aldehyde on the modified cell surfaces to form MCAs. DAB-AM-16 hydrazide with 32 arms demonstrated the best cell aggregation ability as compared to the dendrimer hydrazides with fewer arms, facilitating MCA formation at lower linker concentrations, minimizing cytotoxicity. Characterization of the MCAs formed with 2 μm of DAB-AM-16 hydrazide indicated that the cells proliferated well, maintained 3D cell-cell interaction and 3D cell morphology even as the inter-cellular linker gradually disappeared from the cell surfaces. Cells cultured as MCAs also demonstrated improved cell functions than the cells cultured in 2D monolayer. The dendrimer hydrazides would be a class of consistent, economical, and high performance multivalent transient inter-cellular linkers useful in forming scaffold-free 3D tissue constructs for soft-tissue engineering and regenerative medicine.

Original language	English
Pages (from-to)	3693-3702
Number of pages	10
Journal	Biomaterials
Volume	29
Issue number	27
DOIs	https://doi.org/10.1016/j.biomaterials.2008.05.019
State	Published - Sep 2008
Externally published	Yes

Bibliographical note

Funding Information:
We thank Lijuan He, Wanxin Sun, Yong Xiao, Nikken Wiradharma, Weiping Ye, Junye Xu, Juan Shen and Xiao Fu for stimulating scientific discussions and technical support. This work is supported in part by the Institute of Bioengineering and Nanotechnology, Biomedical Research Council (BMRC), Agency for Science, Technology and Research (A*STAR) of Singapore. Grants from BMRC (R-185-001-045-305), Ministry of Education (R-185-000-135-112), National Medical Research Council (R-185-000-099-213) and Singapore-MIT Alliance Computational and Systems Biology Flagship Project funding to HYU. DZ is a National University of Singapore graduate research scholar.

Keywords

Cell glue
Dendrimer
Multivalent linker
Organ printing
Tissue construct

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2008.05.019

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title = "Dendrimer hydrazides as multivalent transient inter-cellular linkers",

abstract = "Three-dimensional (3D) multi-cellular aggregates (MCAs), as a model scaffold-free tissue construct, are useful for engineering cell-dense and matrix-poor tissues for repair and regeneration applications. To facilitate rapid MCA formation with high degrees of linker consistency and performance, we synthesized a class of dendrimer hydrazides with 8, 16 and 32 arms that can react with the aldehyde on the modified cell surfaces to form MCAs. DAB-AM-16 hydrazide with 32 arms demonstrated the best cell aggregation ability as compared to the dendrimer hydrazides with fewer arms, facilitating MCA formation at lower linker concentrations, minimizing cytotoxicity. Characterization of the MCAs formed with 2 μm of DAB-AM-16 hydrazide indicated that the cells proliferated well, maintained 3D cell-cell interaction and 3D cell morphology even as the inter-cellular linker gradually disappeared from the cell surfaces. Cells cultured as MCAs also demonstrated improved cell functions than the cells cultured in 2D monolayer. The dendrimer hydrazides would be a class of consistent, economical, and high performance multivalent transient inter-cellular linkers useful in forming scaffold-free 3D tissue constructs for soft-tissue engineering and regenerative medicine.",

keywords = "Cell glue, Dendrimer, Multivalent linker, Organ printing, Tissue construct",

author = "Deqiang Zhao and Ong, {Siew Min} and Zhilian Yue and Zhiyong Jiang and Toh, {Yi Chin} and Majad Khan and Jiahua Shi and Tan, {Choon Hong} and Chen, {J. Paul} and Hanry Yu",

note = "Funding Information: We thank Lijuan He, Wanxin Sun, Yong Xiao, Nikken Wiradharma, Weiping Ye, Junye Xu, Juan Shen and Xiao Fu for stimulating scientific discussions and technical support. This work is supported in part by the Institute of Bioengineering and Nanotechnology, Biomedical Research Council (BMRC), Agency for Science, Technology and Research (A*STAR) of Singapore. Grants from BMRC (R-185-001-045-305), Ministry of Education (R-185-000-135-112), National Medical Research Council (R-185-000-099-213) and Singapore-MIT Alliance Computational and Systems Biology Flagship Project funding to HYU. DZ is a National University of Singapore graduate research scholar.",

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AU - Ong, Siew Min

AU - Yue, Zhilian

AU - Jiang, Zhiyong

AU - Toh, Yi Chin

AU - Khan, Majad

AU - Shi, Jiahua

AU - Tan, Choon Hong

AU - Chen, J. Paul

AU - Yu, Hanry

N1 - Funding Information: We thank Lijuan He, Wanxin Sun, Yong Xiao, Nikken Wiradharma, Weiping Ye, Junye Xu, Juan Shen and Xiao Fu for stimulating scientific discussions and technical support. This work is supported in part by the Institute of Bioengineering and Nanotechnology, Biomedical Research Council (BMRC), Agency for Science, Technology and Research (A*STAR) of Singapore. Grants from BMRC (R-185-001-045-305), Ministry of Education (R-185-000-135-112), National Medical Research Council (R-185-000-099-213) and Singapore-MIT Alliance Computational and Systems Biology Flagship Project funding to HYU. DZ is a National University of Singapore graduate research scholar.

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AB - Three-dimensional (3D) multi-cellular aggregates (MCAs), as a model scaffold-free tissue construct, are useful for engineering cell-dense and matrix-poor tissues for repair and regeneration applications. To facilitate rapid MCA formation with high degrees of linker consistency and performance, we synthesized a class of dendrimer hydrazides with 8, 16 and 32 arms that can react with the aldehyde on the modified cell surfaces to form MCAs. DAB-AM-16 hydrazide with 32 arms demonstrated the best cell aggregation ability as compared to the dendrimer hydrazides with fewer arms, facilitating MCA formation at lower linker concentrations, minimizing cytotoxicity. Characterization of the MCAs formed with 2 μm of DAB-AM-16 hydrazide indicated that the cells proliferated well, maintained 3D cell-cell interaction and 3D cell morphology even as the inter-cellular linker gradually disappeared from the cell surfaces. Cells cultured as MCAs also demonstrated improved cell functions than the cells cultured in 2D monolayer. The dendrimer hydrazides would be a class of consistent, economical, and high performance multivalent transient inter-cellular linkers useful in forming scaffold-free 3D tissue constructs for soft-tissue engineering and regenerative medicine.

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JO - Biomaterials

JF - Biomaterials

IS - 27

ER -

Dendrimer hydrazides as multivalent transient inter-cellular linkers

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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