&lt;p&gt;Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis&lt;/p&gt;

Newby, Steven; Masi, Thomas; Griffin, Christopher; King, William J.; Chipman, Anna; Stephenson, Stacy M.; Anderson, David E.; Biris, Alexandru S.; Bourdo, Shawn E.; Dhar, Madhu

doi:10.2147/ijn.s245801

Cited by 40 publications

(43 citation statements)

References 66 publications

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“…Moreover, GDs could regulate the osteogenic differentiation of stem cells from different sources because they could provide stem cells with a unique physical framework comparable to natural extracellular matrix (ECM). [123][124][125] For example, Newby et al 123 prepared GO nanoparticles with oxygen content of 6-10%, then co-cultured them with human mesenchymal stem cells (MSCs), and evaluated the effect of graphene nanoparticles on osteogenic differentiation of these stem cells by alizarin red staining and quantitative analysis. The results showed that the calcium content of MSCs co-cultured with GO nanoparticles was significantly higher than that of cells on the control surface.…”

Section: Improving Functions Of Bone-related Cells In Vitro and Bone mentioning

confidence: 99%

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

Du¹,

Wang

Zhang³

et al. 2020

IJN

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During continuous innovation in the preparation, characterization and application of various bone repair materials for several decades, nanomaterials have exhibited many unique advantages. As a kind of representative two-dimensional nanomaterials, graphene and its derivatives (GDs) such as graphene oxide and reduced graphene oxide have shown promising potential for the application in bone repair based on their excellent mechanical properties, electrical conductivity, large specific surface area (SSA) and atomic structure stability. Herein, we reviewed the updated application of them in bone repair in order to present, as comprehensively, as possible, their specific advantages, challenges and current solutions. Firstly, how their advantages have been utilized in bone repair materials with improved bone formation ability was discussed. Especially, the effects of further functionalization or modification were emphasized. Then, the signaling pathways involved in GDs-induced osteogenic differentiation of stem cells and immunomodulatory mechanism of GDs-induced bone regeneration were discussed. On the other hand, their applications as contrast agents in the field of bone repair were summarized. In addition, we also reviewed the progress and related principles of the effects of GDs parameters on cytotoxicity and residues. At last, the future research was prospected.

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Section: Improving Functions Of Bone-related Cells In Vitro and Bone mentioning

confidence: 99%

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

Du¹,

Wang

Zhang³

et al. 2020

IJN

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“…Therefore, we performed a screen for the expression of several adhesive marker genes, such as Fn1, Vcl, Cd44, and Icam1, in ST2 and MC3T3-E1 cells grown on the collagen-based scaffolds. Fn1 gene encodes fibronectin, which is a ubiquitously expressed, non-collagenous extracellular matrix (ECM) protein with a major role in regulating cell adhesion and differentiation ( Newby et al, 2020 ). Vcl encodes vinculin, which is an essential component of the focal adhesions and associated with both cell-cell and cell-matrix interactions ( Bays and DeMali, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

Positive Effects of Three-Dimensional Collagen-Based Matrices on the Behavior of Osteoprogenitors

Lin

Nica

Sculean

et al. 2021

Front. Bioeng. Biotechnol.

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Recent research has demonstrated that reinforced three-dimensional (3D) collagen matrices can provide a stable scaffold for restoring the lost volume of a deficient alveolar bone. In the present study, we aimed to comparatively investigate the migratory, adhesive, proliferative, and differentiation potential of mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells in response to four 3D collagen-based matrices. Dried acellular dermal matrix (DADM), hydrated acellular dermal matrix (HADM), non-crosslinked collagen matrix (NCM), and crosslinked collagen matrix (CCM) did all enhance the motility of the osteoprogenitor cells. Compared to DADM and NCM, HADM and CCM triggered stronger migratory response. While cells grown on DADM and NCM demonstrated proliferative rates comparable to control cells grown in the absence of a biomaterial, cells grown on HADM and CCM proliferated significantly faster. The pro-proliferative effects of the two matrices were supported by upregulated expression of genes regulating cell division. Increased expression of genes encoding the adhesive molecules fibronectin, vinculin, CD44 antigen, and the intracellular adhesive molecule-1 was detected in cells grown on each of the scaffolds, suggesting excellent adhesive properties of the investigated biomaterials. In contrast to genes encoding the bone matrix proteins collagen type I (Col1a1) and osteopontin (Spp1) induced by all matrices, the expression of the osteogenic differentiation markers Runx2, Alpl, Dlx5, Ibsp, Bglap2, and Phex was significantly increased in cells grown on HADM and CCM only. Short/clinically relevant pre-coating of the 3D biomaterials with enamel matrix derivative (EMD) or recombinant bone morphogenetic protein-2 (rBMP-2) significantly boosted the osteogenic differentiation of both osteoprogenitor lines on all matrices, including DADM and NCM, indicating that EMD and BMP-2 retained their biological activity after being released from the matrices. Whereas EMD triggered the expression of all osteogenesis-related genes, rBMP-2 upregulated early, intermediate, and late osteogenic differentiation markers except for Col1a1 and Spp1. Altogether, our results support favorable influence of HADM and CCM on the recruitment, growth, and osteogenic differentiation of the osteoprogenitor cell types. Furthermore, our data strongly support the biofunctionalization of the collagen-based matrices with EMD or rBMP-2 as a potential treatment modality for bone defects in the clinical practice.

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“…GO-filmed substrates also intensified the differentiation of mouse ESCs to the hematopoietic lineage [ 15 ]. Growing evidence has indicated that a graphene surface provides a biocompatible nanoscale to accelerate the differentiation of human mesenchymal stem cells (hMSCs) into a bone cell specification without cellular toxicity [ 8 , 16 , 17 ]. GO-incorporated poly (lactic-co-glycolic acid) (PLGA) nanofiber structures also enhance the proliferation and osteogenic differentiation of hMSCs [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Performance of the Polydopamine-Graphene Oxide Composite Substrate in the Osteogenic Differentiation of Mouse Embryonic Stem Cells

Shim¹,

Heo²

2021

IJMS

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Graphene oxide (GO) is a biocompatible material considered a favorable stem cell culture substrate. In this study, GO was modified with polydopamine (PDA) to facilitate depositing GO onto a tissue culture polystyrene (PT) surface, and the osteogenic performance of the PDA/GO composite in pluripotent embryonic stem cells (ESCs) was investigated. The surface chemistry of the PDA/GO-coated PT surface was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A high cell viability of ESCs cultured on the PDA/GO composite-coated surface was initially ensured. Then, the osteogenic differentiation of the ESCs in response to the PDA/GO substrate was assessed by alkaline phosphatase (ALP) activity, intracellular calcium levels, matrix mineralization assay, and evaluation of the mRNA and protein levels of osteogenic factors. The culture of ESCs on the PDA/GO substrate presented higher osteogenic potency than that on the uncoated control surface. ESCs cultured on the PDA/GO substrate expressed significantly higher levels of integrin α5 and β1, as well as bone morphogenetic protein receptor (BMPR) types I and II, compared with the control groups. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) was observed in ESCs culture on the PDA/GO substrate. Moreover, BMP signal transduction by SMAD1/5/8 phosphorylation was increased more in cells on PDA/GO than in the control. The nuclear translocation of SMAD1/5/8 in cells was also processed in response to the PDA/GO substrate. Blocking activation of the integrin α5/β1, MAPK, or SMAD signaling pathways downregulated the PDA/GO-induced osteogenic differentiation of ESCs. These results suggest that the PDA/GO composite stimulates the osteogenic differentiation of ESCs via the integrin α5/β1, MAPK, and BMPR/SMAD signaling pathways.

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

Cited by 40 publications

References 66 publications

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

<p>Applications of Graphene and Its Derivatives in Bone Repair: Advantages for Promoting Bone Formation and Providing Real-Time Detection, Challenges and Future Prospects</p>

Positive Effects of Three-Dimensional Collagen-Based Matrices on the Behavior of Osteoprogenitors

Performance of the Polydopamine-Graphene Oxide Composite Substrate in the Osteogenic Differentiation of Mouse Embryonic Stem Cells

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