Arginine–glycine–aspartic acid–polyethylene glycol–polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture

Abstract

The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine–glycine–aspartic acid (RGD) peptide. Our studies demonstrate that RGD–polyethylene glycol (PEG)–PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT–MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.

Dendritic Polymers in Tissue Engineering: Contributions of PAMAM, PPI PEG and PEI to Injury Restoration and Bioactive Scaffold Evolution

“…The same amino acid sequence is a ligand of integrin typically expressed by hepatic cells. Bound to PAMAM via a polyethylene glycol spacer promotes the aggregation of liver cells and their ammonia metabolism function [ 147 ]. Collagen-mimetic dendrimer derivatives may act as cell aggregation moderators too.…”

“…The organization of hepatic cells is the most crucial factor for the assembly of a biological artificial liver system. The three attempts to aggregate hepatic cells without a solid matrix analyzed in the “Dendritic Glues for Cell Aggregation” subsection constitute the background research of the initial approaches in this field [ 145 , 147 , 148 ]. Scaffold technology is once more applied to liver tissue development.…”