Engineering multicellular aggregates with novel dendrimer hydrazides for tissue engineering and drug testing applications

Abstract

<P>INTERCELLULAR LINKER APPROACH IS NOVEL TECHNOLOGY, USEFUL FOR ENGINEERING CELL-DENSE TISSUES LIKE LIVER. IN THIS STUDY, ONE SERIES OF DENDRIMER HYDRAZIDES (4, 8, 16, AND 32 -ARM) WERE SYNTHESIZED AND USED AS INTERCELLULAR LINKERS TO FABRICATE MULTICELLULAR AGGREGATES (MCAS). SYSTEMATIC STUDY DEMONSTRATED THAT HIGH MULTIVALENT DENDRIMER HYDRAZIDE NOT ONLY FACILITATED MCA FORMATION BUT ALSO MET GOOD BIOCOMPATIBILITY REQUIREMENT. THE ENGINEERED MCAS DEMONSTRATED GOOD CELL VIABILITY, PROLIFERATION, TISSUE-LIKE PHENOTYPES, AND IMPROVED CELL FUNCTIONS COMPARED WITH 2-DIMENSIONAL MONOLAYER CELLS, INDICATING ITS USEFULNESS FOR TISSUE ENGINEERING APPLICATIONS. FURTHER ADOPTION OF ENGINEERED MCAS TO TEST TYPICAL METABOLIC DRUGS INDICATED THAT THE ENGINEERED MCAS WERE A MORE SENSITIVE IN VITRO MODEL FOR HEPATOTOXICITY STUDY THAN 2-DIMENSIONAL MONOLAYER CELLS, INDICATING ITS USEFULNESS FOR DRUG TESTING APPLICATIONS. </P>