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      Graphene-Based Scaffolds for Regenerative Medicine

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          Abstract

          Leading-edge regenerative medicine can take advantage of improved knowledge of key roles played, both in stem cell fate determination and in cell growth/differentiation, by mechano-transduction and other physicochemical stimuli from the tissue environment. This prompted advanced nanomaterials research to provide tissue engineers with next-generation scaffolds consisting of smart nanocomposites and/or hydrogels with nanofillers, where balanced combinations of specific matrices and nanomaterials can mediate and finely tune such stimuli and cues. In this review, we focus on graphene-based nanomaterials as, in addition to modulating nanotopography, elastic modulus and viscoelastic features of the scaffold, they can also regulate its conductivity. This feature is crucial to the determination and differentiation of some cell lineages and is of special interest to neural regenerative medicine. Hereafter we depict relevant properties of such nanofillers, illustrate how problems related to their eventual cytotoxicity are solved via enhanced synthesis, purification and derivatization protocols, and finally provide examples of successful applications in regenerative medicine on a number of tissues.

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          Most cited references278

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          Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

          Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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            Matrix elasticity directs stem cell lineage specification.

            Microenvironments appear important in stem cell lineage specification but can be difficult to adequately characterize or control with soft tissues. Naive mesenchymal stem cells (MSCs) are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. During the initial week in culture, reprogramming of these lineages is possible with addition of soluble induction factors, but after several weeks in culture, the cells commit to the lineage specified by matrix elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types. Inhibition of nonmuscle myosin II blocks all elasticity-directed lineage specification-without strongly perturbing many other aspects of cell function and shape. The results have significant implications for understanding physical effects of the in vivo microenvironment and also for therapeutic uses of stem cells.
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              Multilineage potential of adult human mesenchymal stem cells.

              Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                05 February 2021
                February 2021
                : 11
                : 2
                : 404
                Affiliations
                [1 ]Department of Biology, University of Padua, 35131 Padua, Italy; pietro.bellet@ 123456studenti.unipd.it (P.B.); matteo.gasparotto.1@ 123456phd.unipd.it (M.G.)
                [2 ]Department of Chemical Sciences, University of Padua & INSTM, 35131 Padua, Italy; samuel.pressi@ 123456unipd.it (S.P.); anna.fortunato.1@ 123456phd.unipd.it (A.F.)
                [3 ]Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
                Author notes
                Author information
                https://orcid.org/0000-0003-4933-2578
                https://orcid.org/0000-0003-1506-1423
                https://orcid.org/0000-0002-9448-4776
                https://orcid.org/0000-0001-5672-0726
                Article
                nanomaterials-11-00404
                10.3390/nano11020404
                7914745
                33562559
                aa5aa70d-c6e0-4590-a278-f972488502dc
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 December 2020
                : 01 February 2021
                Categories
                Review

                graphene,graphene oxide,reduced graphene oxide,tissue regeneration,2d-scaffolds,hydrogels,fibers,stem cell differentiation

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