Dendrimer hydrazides as multivalent transient inter-cellular linkers.
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 microm 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.
Zhao
Deqiang
D
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore; Department of Chemical and Bio-molecular Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.
Ong
Siew-Min
SM
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, Singapore 117456, Singapore.
Yue
Zhilian
Z
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
Jiang
Zhiyong
Z
Department of Chemistry, Faculty of Science, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
Toh
Yi-Chin
YC
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
Khan
Majad
M
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore.
Shi
Jiahua
J
Department of Chemistry, Faculty of Science, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
Tan
Choon-Hong
CH
Department of Chemistry, Faculty of Science, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
Chen
J Paul
JP
Department of Chemical and Bio-molecular Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore; Division of Environmental Science Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.
Yu
Hanry
H
Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #04-01, 31 Biopolis Way, Singapore 138669, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, Singapore 117456, Singapore; Graduate Program in Bioengineering, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, Singapore 117456, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, #03-03, 2 Medical Drive, Singapore 117597, Singapore; Singapore-MIT Alliance, E4-04-10, 4 Engineering Drive 3, Singapore 117576, Singapore; NUS Tissue-Engineering Programme, DSO Laboratories, National University of Singapore, Singapore 117597, Singapore; Department of Haematology-Oncology, National University Hospital, Singapore 119074, Singapore.
D000418:Albumins / Q000378:metabolism; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared
D000418:Albumins; D050091:Dendrimers; D006834:Hydrazines; D003577:Cytochrome P-450 Enzyme System