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Review
. 2019 Apr 1:14:2281-2299.
doi: 10.2147/IJN.S190928. eCollection 2019.

The effects of graphene and mesenchymal stem cells in cutaneous wound healing and their putative action mechanism

Iwona Lasocka  1 , Elżbieta Jastrzębska  2 , Lidia Szulc-Dąbrowska  3 , Michał Skibniewski  4 , Iwona Pasternak  5 , Marie Hubalek Kalbacova  6   7 , Ewa M Skibniewska  1
Affiliations
Review

The effects of graphene and mesenchymal stem cells in cutaneous wound healing and their putative action mechanism

Iwona Lasocka et al. Int J Nanomedicine. .

Abstract

This study provides a review of the therapeutic potential of graphene dressing scaffolds and mesenchymal stem cells (MSCs) and their synergistic effects with respect to cutaneous wound healing. This study also considers their putative action mechanism based on the antibacterial, immunomodulating, angiogenic, matrix remodeling effects of materials belonging to the graphene family and MSCs during the wound healing process. In addition, this study discusses the cytocompatibility of graphene, its uses as a platform for skin substitutes, the properties it possesses with respect to providing protection against microbial invasion as well as strategies aimed at minimizing the chance of the occurrence of sepsis. MSCs are capable of secreting several factors that exert a therapeutic impact on reparative processes and tissue regeneration. In light of experiments conducted to date, graphene combined with MSCs appears to have the potential to enhance both the wound healing process and infection control at the injury site.

Keywords: graphene; healing; mesenchymal stem cells; wound.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Wound healing stages and the bioactive molecules involved in the healing process. Abbreviations: FGF, fibroblast growth factor; KGF, keratinocyte growth factor; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor; TIMP, tissue inhibitor of metalloproteinase; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor.
Figure 2
Figure 2
Causes and effects of chronic wounds. Abbreviations: ECM, extracellular matrix; TIMP, tissue inhibitor of metalloproteinase.
Figure 3
Figure 3
SEM images recorded using (A) in-lens and (B) ESB detectors with the graphene features marked: the scale bars are 2 µm. Reprinted from Pasternak I. Synthesis and properties of graphene obtained on metallic and germanium substrates by CVD method [unpublished PhD thesis]; 2016; Copyright © 2016 Pasternak. (C) Raman spectra of the graphene. Notes: The three most prominent peaks in the Raman spectrum of graphene consist of the G band at ~1,585 cm−1, the 2D band at ~2,700 cm−1 and the disorder-induced D band at ~1,350 cm−1 (for laser excitation energy of 2.33 eV). The G band, which is related to C−C bond stretching, is caused by the in-plane vibration of sp carbon atoms and corresponds to the first-order Raman-allowed E2g phonon in the center of the Brillouin zone (BZ). The D band, known as the disorder or defect band representing the ring breathing mode (A1g symmetry) of sp carbon rings, is induced by defects in the graphene lattice. The 2D band consists of the second order of the D band, sometimes referred to as an overtone of the D band, and is the result of the two phonon process involving two D phonons from the vicinity of the K point of the BZ. Unlike the D band, it does not need to be activated by proximity to a defect. The intensity ratio of the G and D bands can be used to determine the number of defects in a graphene sample. The number of layers of graphene can be defined on the basis of the line shape of the 2D peak as well as its intensity relative to the G peak. Single-layer graphene is characterized by a sharp, symmetrical, Lorentzian-shaped 2D peak with an intensity greater than that of the G peak. As the number of layers increases, the 2D peak becomes broader and less symmetrical accompanied by a decrease in its intensity. Abbreviation: SEM, scanning electron microscopy.
Figure 4
Figure 4
Mechanotransduction of fibroblasts in response to contact with graphene substrate. Notes: External cues occur in terms of intracellular regulation through a number of signaling cascades including the Rho family GPTase (Rho, Rac and Cdc42) and the activators thereof. These proteins induce the creation of stress fibers and enhanced focal adhesions and lead to the formation of filopodia and lamellipodia.
Figure 5
Figure 5
The immunomodulatory properties of grapheme. Notes: Graphene and its derivatives may act on neutrophiles, inducing neutrophil extracellular traps (NETs) formation. Moreover, graphene induces TLR-dependent activation of NF-κB signaling pathway in macrophages, resulting in polarization of macrophages toward the M1 phenotype and stimulation of secretion of Th1/Th2 cytokines and chemokines. Graphene derivatives also modulate maturation of dendritic cells and their antigen processing and presentation capacity. Abbreviations: DC, dendritic cell; TLR, toll-like receptor.
Figure 6
Figure 6
The effects of MSCs and graphene in the wound healing process. Abbreviations: VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; EGF, epidermal growth factor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; IFNλ, interferon λ; IGF, insulin-like growth factor; KGF, keratinocyte growth factor; MMP-9, matrix metalloproteinase-9; MSC, mesenchymal stem cells; PGE2, prostaglandin E2; RNS, reactive nitrogen species; SDF-1, stromal cell-derived factor-1.
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