Impact of Graphene-Based Surfaces on the Basic Biological Properties of Human Umbilical Cord Mesenchymal Stem Cells: Implications for Ex Vivo Cell Expansion Aimed at Tissue Repair.

Joanna Jagiełło,Monika Dźwigońska,Małgorzata Sekuła-Stryjewska,Edyta Adamczyk,Dariusz Boruczkowski,Magdalena Winkowska-Struzik,Ludwika Lipińska,Sylwia Noga,Magdalena Kurcz,Katarzyna Kurp,Elżbieta Karnas,Ewa K Zuba-Surma,Zbigniew Madeja

doi:10.3390/ijms20184561

Abstract

The potential therapeutic applications of mesenchymal stem/stromal cells (MSCs) and biomaterials have attracted a great amount of interest in the field of biomedical engineering. MSCs are multipotent adult stem cells characterized as cells with specific features, e.g., high differentiation potential, low immunogenicity, immunomodulatory properties, and efficient in vitro expansion ability. Human umbilical cord Wharton’s jelly-derived MSCs (hUC-MSCs) are a new, important cell type that may be used for therapeutic purposes, i.e., for autologous and allogeneic transplantations. To improve the therapeutic efficiency of hUC-MSCs, novel biomaterials have been considered for use as scaffolds dedicated to the propagation and differentiation of these cells. Nowadays, some of the most promising materials for tissue engineering include graphene and its derivatives such as graphene oxide (GO) and reduced graphene oxide (rGO). Due to their physicochemical properties, they can be easily modified with biomolecules, which enable their interaction with different types of cells, including MSCs. In this study, we demonstrate the impact of graphene-based substrates (GO, rGO) on the biological properties of hUC-MSCs. The size of the GO flakes and the reduction level of GO have been considered as important factors determining the most favorable surface for hUC-MSCs growth. The obtained results revealed that GO and rGO are suitable scaffolds for hUC-MSCs. hUC-MSCs cultured on: (i) a thin layer of GO and (ii) an rGO surface with a low reduction level demonstrated a viability and proliferation rate comparable to those estimated under standard culture conditions. Interestingly, cell culture on a highly reduced GO substrate resulted in a decreased hUC-MSCs proliferation rate and induced cell apoptosis. Moreover, our analysis demonstrated that hUC-MSCs cultured on all the tested GO and rGO scaffolds showed no alterations of their typical mesenchymal phenotype, regardless of the reduction level and size of the GO flakes. Thus, GO scaffolds and rGO scaffolds with a low reduction level exhibit potential applicability as novel, safe, and biocompatible materials for utilization in regenerative medicine.

Highlights

Since some of the unusual properties of graphene were examined and described by A
We designed and developed graphene oxide (GO) and reduced graphene oxide surfaces dedicated to the culture and propagation of hUC-mesenchymal stem/stromal cells (MSCs)
Our results indicated that the GO- and reduced graphene oxide (rGO)-based substrates represented suitable surfaces for hUC-MSC growth and led to the maintenance of their typical mesenchymal morphology and phenotype

Summary

Introduction

Since some of the unusual properties of graphene were examined and described by A. Novoselov in 2004, it has emerged as one of the most widely studied carbon nanomaterials [1,2] Due to its two-dimensional structure with carbon atoms arranged in a hexagonal crystal lattice with sp hybridization, graphene has been reported to possess a lot of extraordinary properties, e.g., a large theoretical specific surface area (2630 m2·g−1), high theoretical intrinsic mobility (200,000 cm2·v−1·s−1), high Young s modulus (∼1.0 TPa), high thermal conductivity (∼5000 Wm−1·K−1), high optical transmittance (∼97.7%) [3], low electrical resistivity (10−6 Ω·cm), and electron mobility values reported in excess of 15,000 cm2·v−1·s−1 at room temperature [4]. An increasing amount of attention is being paid to graphene derivatives, such as graphene oxide (GO) and reduced graphene oxide (rGO). Due to their altered structure, with functional oxide groups bound to their surface, they possess properties different from those of ideal graphene, thereby making them suitable for several medical applications [5]. There are different techniques for the reduction of GO: the high reduction of the GO can be achieved by using chemicals, e.g., hydrazine or metal hydrides [8], or the low reduction of the GO may be obtained by using biocompatible compounds, e.g., amino acids [9], carrot root [10], and glucose [11]

Methods

Findings

Discussion

Conclusion