Graphene nanoparticles as osteoinductive and osteoconductive platform for stem cell and bone regeneration

Elkhenany, Hoda; Bourdo, Shawn E.; Hecht, Silke; Donnell, Robert; Gérard, David; Abdelwahed, Ramadan; Lafont, Andersen; Alghazali, Karrer M.; Watanabe, Fumiya; Biris, Alexandru S.; Anderson, David E.; Dhar, Madhu

doi:10.1016/j.nano.2017.05.009

Cited by 51 publications

(55 citation statements)

References 42 publications

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“…Pristine graphene was modified to produce a low-oxygen functionalized form of graphene (LOG) with 6% to 10% oxygen content as reported previously. 24,37 Briefly, graphene nanoplatelets (Product # N002-PDR, 1-1.2 nm thick, ≤10 µm lateral dimensions) were commercially obtained (Angstron Materials, Dayton, OH) and subjected to an aqueous acidic environment ((conc H 2 SO 4 :conc HNO 3 : DI water, volume ratio of 6:2:3) for oxidation.…”

Section: Preparation and Characterization Of Functionalized Graphene mentioning

confidence: 99%

“…26,27 Therefore, despite the concerns due to toxicity, graphenebased nanomaterials and scaffolds have been used successfully in animal and in vitro models of bone defects and assays. [28][29][30][31][32][33][34][35][36][37][38] Even though the results of the in vitro assays and animal models described above are encouraging and strengthen the use of graphene derivatives in biomedicine, the biocompatibility and cytotoxicity of graphene nanoparticles is altered by parameters, such as surface functionalization, shape, size, dose, cell type, and the experimental design. As a result, more research is warranted before the nanoparticles can be used effectively in a human clinical setting.…”

Section: Introductionmentioning

confidence: 99%

“…Our group has demonstrated that a low oxygen (6-10%) functionalized form of graphene nanocomposite (LOGlow-oxygen graphene) is cytocompatible and exhibits osteoinductive effects in vitro and osteoconductive and osseo-integrative effects in vivo when used with fatderived goat MSCs. 29,37 As previously described, the LOG form of nanoparticles are distinct from the commercially available forms of graphene oxide and the reduced graphene oxide, or the carbon-based nanosheets. 24,38 The aim of the current study was to evaluate the effect of lowoxygen graphene nanoparticles on cellular adhesion and osteogenic differentiation of human adipose tissue-derived MSCs (hMSCs), with a focus on the spatiotemporal expression profiles of ECM proteins during these processes.…”

Section: Introductionmentioning

confidence: 99%

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<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

Newby¹,

Masi²,

Griffin³

et al. 2020

IJN

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Purpose: The extracellular matrix (ECM) labyrinthine network secreted by mesenchymal stem cells (MSCs) provides a microenvironment that enhances cell adherence, proliferation, viability, and differentiation. The potential of graphene-based nanomaterials to mimic a tissue-specific ECM has been recognized in designing bone tissue engineering scaffolds. In this study, we investigated the expression of specific ECM proteins when human fat-derived adult MSCs adhered and underwent osteogenic differentiation in the presence of functionalized graphene nanoparticles. Methods: Graphene nanoparticles with 6-10% oxygen content were prepared and characterized by XPS, FTIR, AFM and Raman spectroscopy. Calcein-am and crystal violet staining were performed to evaluate viability and proliferation of human fat-derived MSCs on graphene nanoparticles. Alizarin red staining and quantitation were used to determine the effect of graphene nanoparticles on osteogenic differentiation. Finally, immunofluorescence assays were used to investigate the expression of ECM proteins during cell adhesion and osteogenic differentiation. Results: Our data show that in the presence of graphene, MSCs express specific integrin heterodimers and exhibit a distinct pattern of the corresponding bone-specific ECM proteins, primarily fibronectin, collagen I and vitronectin. Furthermore, MSCs undergo osteogenic differentiation spontaneously without any chemical induction, suggesting that the physicochemical properties of graphene nanoparticles might trigger the expression of bone-specific ECM. Conclusion: Understanding the cell-graphene interactions resulting in an osteogenic niche for MSCs will significantly improve the application of graphene nanoparticles in bone repair and regeneration.

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Section: Preparation and Characterization Of Functionalized Graphene mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

Newby¹,

Masi²,

Griffin³

et al. 2020

IJN

Self Cite

View full text Add to dashboard Cite

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“…The most dominant cell types used in the included articles were mesenchymal stem cells (MSCs), including human adipose-derived stem cells (hADSCs), [17][18][19][20][21][22] Goat ADSCs, 23 human dental pulp stem cells (hDPSCs), 24 human alveolar bone marrow stem cells (hABMSCs), 25 human periodontal ligament stem cells (hPDLSCs), 26,27 and bone MSCs (BMSCs), [28][29][30][31] such as human BMSCs 19, 32-41 (hBMSCs), murine BMSCs (mBMSCs), 4, 42-49 rabbit BMSCs (rBMSCs), 50 murine MSCs cell line C3H10T1/2 51,52 and Caprine BMSCs (cMBSCs). 53 The type of the MSCs in fifteen studies 19,32,36,40,[54][55][56][57][58][59][60][61][62][63][64] was not defined.…”

Section: Cell Sourcesmentioning

confidence: 99%

“…56 Regarding the effect of GO on CS bioactivity, Xie et al 48 observed biomineralized octacalcuim phosphate (OCP), known as a beneficial agent for cell proliferation, 163 on the surface of GO-CS scaffold, significantly enhancing cell proliferation. Oyefusi et al 84 and Nair et al [23] reported that the HAP grafting onto the graphene sheets and incorporating GO nanoflakes into a Gn-HAP matrix enhanced total protein adsorption, as well as cell viability, respectively.…”

Section: Graphene and Mineralsmentioning

confidence: 99%

In vitro effect of graphene structures as an osteoinductive factor in bone tissue engineering: A systematic review

Mohammadrezaei

Golzar

Rad

et al. 2018

J Biomedical Materials Res

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Graphene and its derivatives have been well-known as influential factors in differentiating stem/progenitor cells toward the osteoblastic lineage. However, there have been many controversies in the literature regarding the parameters effect on bone regeneration, including graphene concentration, size, type, dimension, hydrophilicity, functionalization, and composition. This study attempts to produce a comprehensive review regarding the given parameters and their effects on stimulating cell behaviors such as proliferation, viability, attachment and osteogenic differentiation. In this study, a systematic search of MEDLINE database was conducted for in vitro studies on the use of graphene and its derivatives for bone tissue engineering from January 2000 to February 2018, organized according to the PRISMA statement. According to reviewed articles, different graphene derivative, including graphene, graphene oxide (GO) and reduced graphene oxide (RGO) with mass ratio ≤1.5 wt % for all and concentration up to 50 μg/mL for graphene and GO, and 60 μg/mL for RGO, are considered to be safe for most cell types. However, these concentrations highly depend on the types of cells. It was discovered that graphene with lateral size less than 5 µm, along with GO and RGO with lateral dimension less than 1 µm decrease cell viability. In addition, the three-dimensional structure of graphene can promote cell-cell interaction, migration and proliferation. When graphene and its derivatives are incorporated with metals, polymers, and minerals, they frequently show promoted mechanical properties and bioactivity. Last, graphene and its derivatives have been found to increase the surface roughness and porosity, which can highly enhance cell adhesion and differentiation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2284-2343, 2018.

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Graphene‐Based Biomaterials for Bone Regenerative Engineering: A Comprehensive Review of the Field and Considerations Regarding Biocompatibility and Biodegradation

Daneshmandi

Barajaa

Rad

et al. 2020

Adv Healthcare Materials

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Graphene and its derivatives have continued to garner worldwide interest due to their unique characteristics. Having expanded into biomedical applications, there have been efforts to employ their exceptional properties for the regeneration of different tissues, particularly bone. This article presents a comprehensive review on the usage of graphene‐based materials for bone regenerative engineering. The graphene family of materials (GFMs) are used either alone or in combination with other biomaterials in the form of fillers in composites, coatings for both scaffolds and implants, or vehicles for the delivery of various signaling and therapeutic agents. The applications of the GFMs in each of these diverse areas are discussed and emphasis is placed on the characteristics of the GFMs that have implications in this regard. In tandem and of importance, this article evaluates the safety and biocompatibility of the GFMs and carefully elucidates how various factors influence the biocompatibility and biodegradability of this new class of nanomaterials. In conclusion, the challenges and opportunities regarding the use of the GFMs in regenerative engineering applications are discussed, and future perspectives for the developments in this field are proposed.

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Graphene nanoparticles as osteoinductive and osteoconductive platform for stem cell and bone regeneration

Cited by 51 publications

References 42 publications

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

In vitro effect of graphene structures as an osteoinductive factor in bone tissue engineering: A systematic review

Graphene‐Based Biomaterials for Bone Regenerative Engineering: A Comprehensive Review of the Field and Considerations Regarding Biocompatibility and Biodegradation

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