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Graphene-Based Materials: Biological and Biomedical Applications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 54159

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Dr. Massimiliano Papi

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Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Università Cattolica del Sacro Cuore, 00162 Rome, Italy
Interests: 3D bioprinting; drug delivery; graphene; nanoparticles
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Graphene, a single layer of carbon atoms in a closely-packed honeycomb two-dimensional structure, is a new kind of carbon nanostructure material that was produced for the first time in 2004. Graphene has been exploited in many applications, and the use of graphene in the biomedical field is rapidly growing. Recent years have seen the explosion of graphene-based materials biomedical research, owing to the captivating physical and chemical properties of this family of nanomaterials, and thousands of scientific papers have been published since 2010, the year of the Geim and Novoselov Graphene Nobel Prize.

The versatile chemistry of graphene-based nanomaterials, including the capability to conjugate with water-soluble and water-insoluble active compounds, DNA, proteins, cells, targeting agents or polymers makes them a desirable nanoplatform for advanced biotechnological applications. Graphene derivates can be designed for drug and gene delivery applications or to realize antibacterial biocompatible scaffolds for the growth and proliferation of human stem cells. The graphene capability to confine light opens the possibility to develop ultrasensitive biosensors and can be applied for therapeutic functions together with imaging capabilities. Since graphene and graphene derivatives are a versatile platform across various biomedical disciplines, in this Special Issue, we aim to illustrate areas of promise and identify future challenges.

Prof. Massimiliano Papi
Guest Editor

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Keywords

Graphene
Graphene oxide
Drug delivery
Gene delivery
Antimicrobial
Tissue engineering
Biosensor
Imaging
Theranostics
Photothermal therapy

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 179 KiB

Open AccessEditorial

Graphene-Based Materials: Biological and Biomedical Applications

by Massimiliano Papi

Int. J. Mol. Sci. 2021, 22(2), 672; https://doi.org/10.3390/ijms22020672 - 12 Jan 2021

Cited by 11 | Viewed by 2287

Abstract

This editorial aims to summarize the eleven scientific papers published in the Special Issue “Graphene-Based Materials: Biological and Biomedical Applications” [...] Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

Research

Jump to: Editorial, Review

10 pages, 1088 KiB

Open AccessArticle

Osteogenic Properties of 3D-Printed Silica-Carbon-Calcite Composite Scaffolds: Novel Approach for Personalized Bone Tissue Regeneration

by Parastoo Memarian, Francesco Sartor, Enrico Bernardo, Hamada Elsayed, Batur Ercan, Lucia Gemma Delogu, Barbara Zavan and Maurizio Isola

Int. J. Mol. Sci. 2021, 22(2), 475; https://doi.org/10.3390/ijms22020475 - 6 Jan 2021

Cited by 15 | Viewed by 3332

Abstract

Carbon enriched bioceramic (C-Bio) scaffolds have recently shown exceptional results in terms of their biological and mechanical properties. The present study aims at assessing the ability of the C-Bio scaffolds to affect the commitment of canine adipose-derived mesenchymal stem cells (cAD-MSCs) and investigating the influence of carbon on cell proliferation and osteogenic differentiation of cAD-MSCs in vitro. The commitment of cAD-MSCs to an osteoblastic phenotype has been evaluated by expression of several osteogenic markers using real-time PCR. Biocompatibility analyses through 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) activity, hemolysis assay, and Ames test demonstrated excellent biocompatibility of both materials. A significant increase in the extracellular alkaline phosphatase (ALP) activity and expression of runt-related transcription factor (RUNX), ALP, osterix (OSX), and receptor activator of nuclear factor kappa-Β ligand (RANKL) genes was observed in C-Bio scaffolds compared to those without carbon (Bio). Scanning electron microscopy (SEM) demonstrated excellent cell attachment on both material surfaces; however, the cellular layer on C-Bio fibers exhibited an apparent secretome activity. Based on our findings, graphene can improve cell adhesion, growth, and osteogenic differentiation of cAD-MSCs in vitro. This study proposed carbon as an additive for a novel three-dimensional (3D)-printable biocompatible scaffold which could become the key structural material for bone tissue reconstruction. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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17 pages, 2522 KiB

Open AccessArticle

Graphene Quantum Dots’ Surface Chemistry Modulates the Sensitivity of Glioblastoma Cells to Chemotherapeutics

by Giordano Perini, Valentina Palmieri, Gabriele Ciasca, Marcello D’Ascenzo, Jacopo Gervasoni, Aniello Primiano, Monica Rinaldi, Daniela Fioretti, Chiara Prampolini, Federica Tiberio, Wanda Lattanzi, Ornella Parolini, Marco De Spirito and Massimiliano Papi

Int. J. Mol. Sci. 2020, 21(17), 6301; https://doi.org/10.3390/ijms21176301 - 31 Aug 2020

Cited by 40 | Viewed by 3646

Abstract

Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood–brain barrier, the barrier that reduces cancer therapy efficacy. Here, we tested three alternative GQDs’ surface chemistries on two neural lineages (glioblastoma cells and mouse cortical neurons). We showed that surface chemistry modulates GQDs’ biocompatibility. When used in combination with the chemotherapeutic drug doxorubicin, GDQs exerted a synergistic effect on tumor cells, but not on neurons. This appears to be mediated by the modification of membrane permeability induced by the surface of GQDs. Our findings highlight that GQDs can be adopted as a suitable delivery and therapeutic strategy for the treatment of glioblastoma, by both directly destabilizing the cell membrane and indirectly increasing the efficacy of chemotherapeutic drugs. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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16 pages, 4119 KiB

Open AccessArticle

Graphene Oxide Scaffold Stimulates Differentiation and Proangiogenic Activities of Myogenic Progenitor Cells

by Mateusz Wierzbicki, Anna Hotowy, Marta Kutwin, Sławomir Jaworski, Jaśmina Bałaban, Malwina Sosnowska, Barbara Wójcik, Aleksandra Wędzińska, André Chwalibog and Ewa Sawosz

Int. J. Mol. Sci. 2020, 21(11), 4173; https://doi.org/10.3390/ijms21114173 - 11 Jun 2020

Cited by 19 | Viewed by 3683

Abstract

The physiological process of muscle regeneration is quite limited due to low satellite cell quantity and also the inability to regenerate and reconstruct niche tissue. The purpose of the study was to examine whether a graphene oxide scaffold is able to stimulate myogenic progenitor cell proliferation and the endocrine functions of differentiating cells, and therefore, their active participation in the construction of muscle tissue. Studies were carried out using mesenchymal cells taken from 6-day-old chicken embryos and human umbilical vein endothelial cells (HUVEC) were used to assess angiogenesis. The graphene scaffold was readily colonized by myogenic progenitor cells and the cells dissected from heart, brain, eye, and blood vessels did not avoid the scaffold. The scaffold strongly induced myogenic progenitor cell signaling pathways and simultaneously activated proangiogenic signaling pathways via exocrine vascular endothelial growth factor (VEGF) secretion. The present study revealed that the graphene oxide (GO) scaffold initiates the processes of muscle cell differentiation due to mechanical interaction with myogenic progenitor cell. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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19 pages, 5854 KiB

Open AccessArticle

Interaction Analysis of Commercial Graphene Oxide Nanoparticles with Unicellular Systems and Biomolecules

by Brixhilda Domi, Carlos Rumbo, Javier García-Tojal, Livia Elena Sima, Gabriela Negroiu and Juan Antonio Tamayo-Ramos

Int. J. Mol. Sci. 2020, 21(1), 205; https://doi.org/10.3390/ijms21010205 - 27 Dec 2019

Cited by 22 | Viewed by 4657

Abstract

The ability of commercial monolayer graphene oxide (GO) and graphene oxide nanocolloids (GOC) to interact with different unicellular systems and biomolecules was studied by analyzing the response of human alveolar carcinoma epithelial cells, the yeast Saccharomyces cerevisiae and the bacteria Vibrio fischeri to the presence of different nanoparticle concentrations, and by studying the binding affinity of different microbial enzymes, like the α-l-rhamnosidase enzyme RhaB1 from the bacteria Lactobacillus plantarum and the AbG β-d-glucosidase from Agrobacterium sp. (strain ATCC 21400). An analysis of cytotoxicity on human epithelial cell line A549, S. cerevisiae (colony forming units, ROS induction, genotoxicity) and V. fischeri (luminescence inhibition) cells determined the potential of both nanoparticle types to damage the selected unicellular systems. Also, the protein binding affinity of the graphene derivatives at different oxidation levels was analyzed. The reported results highlight the variability that can exist in terms of toxicological potential and binding affinity depending on the target organism or protein and the selected nanomaterial. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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16 pages, 6893 KiB

Open AccessArticle

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

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

Int. J. Mol. Sci. 2019, 20(18), 4561; https://doi.org/10.3390/ijms20184561 - 14 Sep 2019

Cited by 25 | Viewed by 3490

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. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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13 pages, 2252 KiB

Open AccessCommunication

The Use of TAT Peptide-Functionalized Graphene as a Highly Nuclear-Targeting Carrier System for Suppression of Choroidal Melanoma

by Suyan Shan, Shujuan Jia, Tom Lawson, Lu Yan, Mimi Lin and Yong Liu

Int. J. Mol. Sci. 2019, 20(18), 4454; https://doi.org/10.3390/ijms20184454 - 10 Sep 2019

Cited by 21 | Viewed by 2939

Abstract

Tumorous metastasis is a difficult challenge to resolve for researchers and for clinicians. Targeted delivery of antitumor drugs towards tumor cells’ nuclei can be a practical approach to resolving this issue. This work describes an efficient nuclear-targeting delivery system prepared from trans-activating transcriptional activator (TAT) peptide-functionalized graphene nanocarriers. The TAT peptide, originally observed in a human immunodeficiency virus 1 (HIV-1), was incorporated with graphene via an edge-functionalized ball-milling method developed by the author’s research group. High tumor-targeting capability of the resulting nanocarrier was realized by the strong affinity between TAT and the nuclei of cancer cells, along with the enhanced permeability and retention (EPR) effect of two-dimensional graphene nanosheets. Subsequently, a common antitumor drug, mitomycin C (MMC), was covalently linked to the TAT-functionalized graphene (TG) to form a nuclear-targeted nanodrug MMC-TG. The presence of nanomaterials inside the nuclei of ocular choroidal melanoma (OCM-1) cells was shown using transmission electron microscopy (TEM) and confocal laser scanning microscopy. In vitro results from a Transwell co-culture system showed that most of the MMC-TG nanodrugs were delivered in a targeted manner to the tumorous OCM-1 cells, while a very small amount of MMC-TG was delivered in a non-targeted manner to normal human retinal pigment epithelial (ARPE-19) cells. TEM results further confirmed that apoptosis of OCM-1 cells was started from the lysis of nuclear substances, followed by the disappearance of nuclear membrane and cytoplasm. This suggests that the as-synthesized MMC-TG is a promising nuclear-target nanodrugfor resolution of tumorous metastasis issues at the headstream. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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14 pages, 22087 KiB

Open AccessArticle

Carbon Nanomaterials and LED Irradiation as Antibacterial Strategies against Gram-Positive Multidrug-Resistant Pathogens

by Lisa Elias, Rafael Taengua, Belén Frígols, Beatriz Salesa and Ángel Serrano-Aroca

Int. J. Mol. Sci. 2019, 20(14), 3603; https://doi.org/10.3390/ijms20143603 - 23 Jul 2019

Cited by 32 | Viewed by 4584

Abstract

Background: Due to current antibiotic resistance worldwide, there is an urgent need to find new alternative antibacterial approaches capable of dealing with multidrug-resistant pathogens. Most recent studies have demonstrated the antibacterial activity and non-cytotoxicity of carbon nanomaterials such as graphene oxide (GO) and carbon nanofibers (CNFs). On the other hand, light-emitting diodes (LEDs) have shown great potential in a wide range of biomedical applications. Methods: We investigated a nanotechnological strategy consisting of GO or CNFs combined with light-emitting diod (LED) irradiation as novel nanoweapons against two clinically relevant Gram-positive multidrug-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). The cytotoxicity of GO and CNFs was studied in the presence of human keratinocyte HaCaT cells. Results: GO or CNFs exhibited no cytotoxicity and high antibacterial activity in direct contact with MRSE and MRSA cells. Furthermore, when GO or CNFs were illuminated with LED light, the MRSE and MRSA cells lost viability. The rate of decrease in colony forming units from 0 to 3 h, measured per mL, increased to 98.5 ± 1.6% and 95.8 ± 1.4% for GO and 99.5 ± 0.6% and 99.7 ± 0.2% for CNFs. Conclusions: This combined antimicrobial approach opens up many biomedical research opportunities and provides an enhanced strategy for the prevention and treatment of Gram-positive multidrug-resistant infections. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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Review

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25 pages, 10473 KiB

Open AccessReview

Unravelling the Potential of Graphene Quantum Dots in Biomedicine and Neuroscience

by Giordano Perini, Valentina Palmieri, Gabriele Ciasca, Marco De Spirito and Massimiliano Papi

Int. J. Mol. Sci. 2020, 21(10), 3712; https://doi.org/10.3390/ijms21103712 - 25 May 2020

Cited by 85 | Viewed by 8539

Abstract

Quantum dots (QDs) are semiconducting nanoparticles that have been gaining ground in various applications, including the biomedical field, thanks to their unique optical properties. Recently, graphene quantum dots (GQDs) have earned attention in biomedicine and nanomedicine, thanks to their higher biocompatibility and low cytotoxicity compared to other QDs. GQDs share the optical properties of QD and have proven ability to cross the blood-brain barrier (BBB). For this reason, GQDs are now being employed to deepen our knowledge in neuroscience diagnostics and therapeutics. Their size and surface chemistry that ease the loading of chemotherapeutic drugs, makes them ideal drug delivery systems through the bloodstream, across the BBB, up to the brain. GQDs-based neuroimaging techniques and theranostic applications, such as photothermal and photodynamic therapy alone or in combination with chemotherapy, have been designed. In this review, optical properties and biocompatibility of GQDs will be described. Then, the ability of GQDs to overtake the BBB and reach the brain will be discussed. At last, applications of GQDs in bioimaging, photophysical therapies and drug delivery to the central nervous system will be considered, unraveling their potential in the neuroscientific field. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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17 pages, 4265 KiB

Open AccessReview

Graphene Oxide–Based Nanomaterials: An Insight into Retinal Prosthesis

by Jia-Wei Yang, Zih-Yu Yu, Sheng-Jen Cheng, Johnson H. Y. Chung, Xiao Liu, Chung-Yu Wu, Shien-Fong Lin and Guan-Yu Chen

Int. J. Mol. Sci. 2020, 21(8), 2957; https://doi.org/10.3390/ijms21082957 - 22 Apr 2020

Cited by 19 | Viewed by 5420

Abstract

Retinal prosthesis has recently emerged as a treatment strategy for retinopathies, providing excellent assistance in the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa. The potential application of graphene oxide (GO), a highly biocompatible nanomaterial with superior physicochemical properties, in the fabrication of electrodes for retinal prosthesis, is reviewed in this article. This review integrates insights from biological medicine and nanotechnology, with electronic and electrical engineering technological breakthroughs, and aims to highlight innovative objectives in developing biomedical applications of retinal prosthesis. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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25 pages, 2906 KiB

Open AccessReview

Review of Polarization Optical Devices Based on Graphene Materials

by Shijie Zhang, Zongwen Li and Fei Xing

Int. J. Mol. Sci. 2020, 21(5), 1608; https://doi.org/10.3390/ijms21051608 - 26 Feb 2020

Cited by 48 | Viewed by 6584

Abstract

Graphene has received extensive scholarly attention for its extraordinary optical, electrical, and physicochemical properties, as well as its compatibility with silicon-based semiconductor processes. As a unique two-dimensional atomic crystal material, graphene has excellent mechanical properties, ultra-high carrier mobility, ultra-wide optical response spectrum, and strong polarization dependence effect, which make it have great potential in new optical and polarization devices. A series of new optical devices that are based on graphene have been developed, showing excellent performance and broad application prospects. In this paper, the recent research progress of polarizers, sensors, modulators, and detectors that are based on the polarization characteristics of graphene is reviewed. In particular, the polarization dependence effect and broadband absorption enhancement of graphene under total reflection structure are emphasized, which enhance the interaction between graphene and light and then provide a new direction for research of graphene polarization devices. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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17 pages, 1933 KiB

Open AccessReview

Functional Magnetic Graphene Composites for Biosensing

by Fan Li, Yan Huang, Kai Huang, Jing Lin and Peng Huang

Int. J. Mol. Sci. 2020, 21(2), 390; https://doi.org/10.3390/ijms21020390 - 8 Jan 2020

Cited by 32 | Viewed by 4142

Abstract

Magnetic graphene composites (MGCs), which are composed of magnetic nanoparticles with graphene or its derivatives, played an important role in sensors development. Due to the enhanced electronic properties and the synergistic effect of magnetic nanomaterials and graphene, MGCs could be used to realize more efficient sensors such as chemical, biological, and electronic sensors, compared to their single component alone. In this review, we first reviewed the various routes for MGCs preparation. Then, sensors based on MGCs were discussed in different groups, including optical sensors, electrochemical sensors, and others. At the end of the paper, the challenges and opportunities for MGCs in sensors implementation are also discussed. Full article

(This article belongs to the Special Issue Graphene-Based Materials: Biological and Biomedical Applications)

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