Selective Regulation of Neurons, Glial Cells, and Neural Stem/Precursor Cells by Poly(allylguanidine)-Coated Surfaces

Abstract

Poly(allylguanidine) (PAG) was synthesized and characterized as a polycationic coating material for culturing neurons, glial cells, and neural stem/precursor cells (NSPCs) to apply PAG for neural tissue engineering. For comparison, poly-D-lysine (PDL), the golden benchmark of the neuron cell culture system, was also used in this study. When PAG was subjected to a mixed culture of neurons and glial cells, cell adhesion and neurite extension of neuronal cells were clearly observed but only few glial cells could be found alongside the neurons. Compared to PDL, the significantly lower density of the glial fibrillary acidic protein-positive cells implied that PAG suppressed the glial cell development. Likewise, PAG was demonstrated to dominate the differentiation of NSPCs principally into neurons. To investigate whether the different effects of PAG and PDL on neuron and glial cell behaviors resulted from the difference of guanidinium cations and ammonium cations, poly-L-arginine (PLA) was included and compared in this study. Similar to PDL, PLA supported high neuron and glial cell viability simultaneously. Consequently, glial cell growth and viability restrained on PAG was not only affected by the side-chain guanidino groups but also by the backbone structure property. The absence of the peptide structure in the backbone of PAG and the conformation of coated PAG on tissue culture polystyrene possibly determined the polycationic biomaterial to limit the growth of glial cells.

Dendritic Polyglycerol Amine: An Enhanced Substrate to Support Long-Term Neural Cell Culture

“…Examination of the culture via phase-contrast imaging before fixation showed a similar sparse distribution of surviving neurons, indicating that the few cells present after immunolabeling are not due to cellular detachment during the fixation, washing and labeling steps, but rather reflect the inability of cells to adhere and survive on a minimally coated glass surface. Certain polycationic surface coatings may impact the proliferation or differentiation of either neurons or glia ( Ji et al, 2019 ). However, few S100β positive glial cell bodies were present in these 7 DIV cultures, and the few cells detected did not appear to be significantly affected by the type of substrate used (data not shown).…”

“…While the coatings initially used for neuronal cultures were either proteins or polypeptides, other synthetic/non-peptide cationic linear polymers have been investigated for their capacity to support neuronal adhesion and growth ( Ji et al, 2019 ; Lakard et al, 2005 ; Landry et al, 2018 ; Schmidt et al, 1997 ; Vancha et al, 2004 ). dPGA belongs to a class of purely synthetic highly branched polymers.…”

“…Poly-lysine and poly-ornithine are homopolymeric chains of a basic amino acid that were selected based on early observations that proteins with a high content of positively charged amino acids, such as histones and protamine, when adsorbed onto a cell culture substrate would support cell adhesion and proliferation ( McKeehan & Ham, 1976 ). More recent studies have reported that non-peptide polymers such as polyethyleneimine ( Vancha et al, 2004 ), polypropyleneimine ( Lakard et al, 2005 ), polypyrrole ( Schmidt et al, 1997 ), poly(allylguanidine) ( Ji et al, 2019 ) and poly-electrolyte multilayers (PEMs) ( Landry et al, 2018 ) can function as substrates to support neural cell culture. The unifying characteristic of these polymers is that they all contain basic amine functional groups, suggesting that a relatively high density of positive charge at physiological pH is the key parameter to promote cell adherence to the surface.…”

Highly Ordered 3D Tissue Engineering Scaffolds as a Versatile Culture Platform for Nerve Cells Growth

“…Various scaffolds used for growing nerve cells have been functionalized with bioactive molecules. [67,68] However, the effects of different scaffold surface modifications on nerve cell growth are not known. Nerve cell behavior can be regulated by the physicochemical properties of the modified scaffold surface, which would result in altered regeneration efficiency of the damaged peripheral nerve.…”

Poly(allylguanidine)-Coated Surfaces Regulate TGF-β in Glioblastoma Cells to Induce Apoptosis via NF-κB Pathway Activation

“…In addition, the guanidine group demonstrates fine affinity with the phosphate group where PAG could strongly contact the cell membrane to affect the cell fate. Furthermore, our previous study indicated that PAG promotes neural viability and induces neural stem/precursor cells (NSPCs) to differentiate into neurons . Nonetheless, the exact mechanism behind the anti-cancer effects of PAG is not well understood.…”