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 journalArticlepeer-review

20 Scopus citations


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 languageEnglish
Pages (from-to)3693-3702
Number of pages10
Issue number27
StatePublished - Sep 2008
Externally publishedYes


  • Cell glue
  • Dendrimer
  • Multivalent linker
  • Organ printing
  • Tissue construct

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