The Promotion of Human Neural Stem Cells Adhesion Using Bioinspired Poly(norepinephrine) Nanoscale Coating

Abstract

The establishment of versatile biomaterial interfaces that can facilitate cellular adhesion is crucial for elucidating the cellular processes that occur on biomaterial surfaces. Furthermore, biomaterial interfaces can provide physical or chemical cues that are capable of stimulating cellular behaviors by regulating intracellular signaling cascades. Herein, a method of creating a biomimetic functional biointerface was introduced to enhance human neural stem cell (hNSC) adhesion. The hNSC-compatible biointerface was prepared by the oxidative polymerization of the neurotransmitter norepinephrine, which generates a nanoscale organic thin layer, termed poly(norepinephrine) (pNE). Due to its adhesive property, pNE resulted in an adherent layer on various substrates, and pNE-coated biointerfaces provided a highly favorable microenvironment for hNSCs, with no observed cytotoxicity. Only a 2-hour incubation of hNSCs was required to firmly attach the stem cells, regardless of the type of substrate. Importantly, the adhesive properties of pNE interfaces led to micropatterns of cellular attachment, thereby demonstrating the ability of the interface to organize the stem cells. This highly facile surface-modification method using a biomimetic pNE thin layer can be applied to a number of suitable materials that were previously not compatible with hNSC technology.

Microenvironments Designed to Support Growth and Function of Neuronal Cells

“…These positively charged layers interact with the negatively charged cellular membrane and allow cell attachment. Reactive polycatechol coatings like poly(dopamine) or poly(norepinephrine) (pNE) have also been used to immobilize neurons (Park et al, 2014;Kim et al, 2015). Such coatings can form on almost any kind of material.…”

“…Such coatings can form on almost any kind of material. The polycatechol layer can covalently react with proteins from serum forming a protein layer onto the biomaterial that supports fast adhesion of human neural stem cells (hNSCs) ( Figure 1A), or bind secreted adhesive proteins from the cells, or directly bind to the surface of the cells (Park et al, 2014).…”

“…In a different study, adult hippocampal NSCs FIGURE 1 | Strategies to support adhesion of neuronal cells to biomaterials (A) hNSCs on pNE coated and uncoated substrates. pNE coating after 2 h of cell seeding significantly enhance cell adhesion (Park et al, 2014) Copyright 2014, Minah Park et al; (B) PLLA nanofibers coated or covalently functionalized with LN. LN coated substrates support adhesion and neurite extension of PC12 cells (Koh et al, 2008) Copyright 2008, Elsevier; (C) PAs (Palmitoyl-VVAAEE-NH 2 ) functionalized with adhesive epitope to support adhesion of hippocampal neurons.…”

A chemically defined substrate for the expansion and neuronal differentiation of human pluripotent stem cell-derived neural progenitor cells

“…Several groups have reported the culture and differentiation of fetal or adult neural stem cells (NSCs) on polymerbased substrates (Park et al, 2014;Little et al, 2008;Bhang et al, 2007;Lundin et al, 2011;Saha et al, 2007). It is important to point out that the NSCs used in these studies, which can be isolated from numerous species and various regions in the fetal and adult nervous system, are biologically and developmentally distinct from the hNPCs used in this study (Kornblum, 2007;Temple, 2001).…”

Melanin and Melanin-Like Hybrid Materials in Regenerative Medicine

“…Notably, PDA structural properties can be tailored on specific application requirements by varying the synthetic conditions (i.e., DA concentration or buffer composition) [ 33 ]. Recently, norepinephrine (also known as noradrenaline), a neurotransmitter and vasopressor moiety, widely employed in medicine, has been proposed as a novel melanogenic precursor [ 34 , 35 ]. It undergoes oxidative polymerization forming both monodisperse nanoparticles [ 34 ] and thin coatings, with tough adhesive properties on different substrates.…”