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

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.

Synthesis and Characterization of Graphene Oxide and Reduced Graphene Oxide Composites with Inorganic Nanoparticles for Biomedical Applications

“…Moreover, three different routes of silver nanoparticle synthesis were compared in the creation of the desired homogenous composites with flake graphene. The forms of graphene used (graphene oxide and slightly reduced graphene oxide) are known to be nontoxic towards human cells, for example, mesenchymal stem cells, a finding that was confirmed in our previous work [ 7 ]. This manuscript provides a broad morphological and chemical description of each of the inorganic particles and composites produced in this study.…”

“…The biocompatibility of these two graphene derivatives has been confirmed by many publications in the literature [ 6 ]. This aspect of GO and RGO materials presented in this study was also previously investigated by us with human umbilical cord mesenchymal stem cells (hUC-MSCs) [ 7 ]. The overriding conclusion from this study was that none of the tested materials (GO and RGO) were characterized with a negative impact in the cellular viability, proliferation, morphology, or gene expression.…”

Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells

“…Numerous studies have shown that hUC-MSCs have significant immune modulation and tissue repair functions due to their low immunogenicity [14][15][16]. As an ideal candidate for allogenic adoptive transfer therapy, hUC-MSCs have been shown to play a protective role in A/H5N1-associated acute lung injury [17].…”

Gradient Chitosan Hydrogels Modified with Graphene Derivatives and Hydroxyapatite: Physiochemical Properties and Initial Cytocompatibility Evaluation

“…Undoubtedly, it is due to the fact that graphene family materials (GFM) [ 22 ] are unique in so many ways. From graphene, a one-atom-thick sheet of sp 2 -bonded carbon atoms arranged in a honeycomb lattice, to its various derivatives produced by chemical or physical modifications, GFM are known for their exceptional mechanical properties, high thermal and electrical conductivity, high chemical stability, high optical transmittance, large surface area, and many other, often tunable, properties that are exploited in vast number of applications [ 23 , 24 , 25 ]. However, in biomedical fields, two of them, i.e., graphene oxide (GO) and reduced graphene oxide (rGO), are of particular interest.…”