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Peptide- and Protein-Graphene Oxide Conjugate Materials for Controlling Mesenchymal Stem Cell Fate

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Abstract

Stem cells hold great potential in tissue engineering due to their prolonged self-renewal and ability to differentiate into a variety of cell lines. Leveraging stem cells in regenerative healing requires the ability to support stem cell vitality, localize and retain the stem cells at the site where they are needed, and control their differentiation into specified cell types. To address these needs, graphene oxide (GO), a two-dimensional nanocarbon material, has been widely investigated due to its unique structural characteristics that interface with biomolecules and impart cytocompatibility. To expand on the utility of GO in tissue engineering applications, researchers have incorporated GO with peptides and proteins to provide an additional level of control over stem cell fate. This review focuses on how peptide- and protein-GO conjugates are utilized for stem cell instruction, growth, delivery, and retention in the following ways: GO as a delivery vehicle for stem cell-inducing proteins; peptide- and protein-GO conjugates as two- or three-dimensional cell scaffolds; and GO as an additive in peptide- and protein-based hydrogels. These technologies highlight the value that peptide- and protein-GO conjugates possess in addressing the challenges associated with stem cell therapies. Future directions for the continued research of peptide- and protein-GO conjugates are projected as we look to further advance the field of regenerative tissue engineering using these powerful hybrid materials.

Lay Summary

Stem cell therapies can be used to replace or rebuild damaged tissue through natural healing pathways. However, using stem cells in tissue engineering requires novel technologies that control stem cell fate. Hybrid materials comprised of graphene oxide (GO) and proteins represent a promising new technology with the ability to interface with stem cells. In these systems, the GO acts as a scaffold for cell growth and supports the protein which, in turn, supplies the appropriate chemical cues to direct stem cell fate toward regenerative healing.

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References

  1. Kaul H, Ventikos Y. On the genealogy of tissue engineering and regenerative medicine. Tissue Eng Part B Rev. 2015;21:203–17.

    Google Scholar 

  2. Siminovitch L, McCulloch EA, Till JE. The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol. 1963;62:327–36.

    CAS  Google Scholar 

  3. Becker AJ, McCulloch EA, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature Nature Publishing Group. 1963;197:452–4.

    CAS  Google Scholar 

  4. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm Lond Engl. 2005;2:8.

    Google Scholar 

  5. Nadig RR. Stem cell therapy—hype or hope? A review. J Conserv Dent JCD. 2009;12:131–8.

    Google Scholar 

  6. Zakrzewski W, Dobrzyński M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther. 2019;10:68.

    CAS  Google Scholar 

  7. Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol Nature Publishing Group. 2016;17:170–82.

    CAS  Google Scholar 

  8. Elbuluk A, Einhorn TA, Iorio R. A comprehensive review of stem-cell therapy. JBJS Rev. 2017;5:15.

    Google Scholar 

  9. Dubey NK, Mishra VK, Dubey R, Syed-Abdul S, Wang JR, Wang PD, et al. Combating osteoarthritis through stem cell therapies by rejuvenating cartilage: a review. Stem Cells Int. 2018;2018:1–13. https://doi.org/10.1155/2018/5421019.

    Article  CAS  Google Scholar 

  10. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm. 2005;2:8.

    Google Scholar 

  11. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif. 1970;3:393–403.

    CAS  Google Scholar 

  12. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. Development The Company of Biologists Ltd. 1966;16:381–90.

    CAS  Google Scholar 

  13. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968;6:230–47.

    CAS  Google Scholar 

  14. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol Nature Publishing Group. 2008;8:726–36.

    CAS  Google Scholar 

  15. Williams AR, Hare JM, Stefanie D, Douglas L. Mesenchymal stem cells. Circ Res American Heart Association. 2011;109:923–40.

    CAS  Google Scholar 

  16. McKee C, Chaudhry GR. Advances and challenges in stem cell culture. Colloids Surf B: Biointerfaces. 2017;159:62–77.

    CAS  Google Scholar 

  17. Tuan RS, Boland G, Tuli R. Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther. 2002;5:32.

    Google Scholar 

  18. Kenry LWC, Loh KP, Lim CT. When stem cells meet graphene: opportunities and challenges in regenerative medicine. Biomaterials. 2018;155:236–50.

    CAS  Google Scholar 

  19. Burdick JA, Mauck RL, Gerecht S. To serve and protect: hydrogels to improve stem cell-based therapies. Cell Stem Cell. 2016;18:13–5.

    CAS  Google Scholar 

  20. Pawelec G, Rehbein A, Schlotz E, Friccius H, Pohla H. Cytokine modulation of TH1/TH2 phenotype differentiation in directly alloresponsive CD4+ human T cells. Transplantation. 1996;62:1095–101.

    CAS  Google Scholar 

  21. Diaz-Rodriguez P, Erndt-Marino J, Chen H, Diaz-Quiroz JF, Samavedi S, Hahn MS. A bioengineered in vitro osteoarthritis model with tunable inflammatory environments indicates context-dependent therapeutic potential of human mesenchymal stem cells. Regen Eng Transl Med. 2019;5:297–307.

    CAS  Google Scholar 

  22. Han J, Kim YS, Lim M-Y, Kim HY, Kong S, Kang M, et al. Dual roles of Graphene oxide to attenuate inflammation and elicit timely polarization of macrophage phenotypes for cardiac repair. ACS Nano American Chemical Society. 2018;12:1959–77.

    CAS  Google Scholar 

  23. Zheng Y, Pescatore N, Gogotsi Y, Dyatkin B, Ingavle G, Mochalin V, et al. Rapid adsorption of proinflammatory cytokines by graphene nanoplatelets and their composites for extracorporeal detoxification. J Nanomater. 2018;2018:1–13. https://doi.org/10.1155/2018/5421019.

    Article  CAS  Google Scholar 

  24. Oryan A, Baghaban Eslaminejad M, Kamali A, Hosseini S, Moshiri A, Baharvand H. Mesenchymal stem cells seeded onto tissue-engineered osteoinductive scaffolds enhance the healing process of critical-sized radial bone defects in rat. Cell Tissue Res. 2018;374:63–81.

    CAS  Google Scholar 

  25. Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, et al. Vascularized and complex organ buds from diverse tissues via mesenchymal cell-driven condensation. Cell Stem Cell. 2015;16:556–65.

    CAS  Google Scholar 

  26. Fuentes-Mera L, Camacho A, Moncada-Saucedo NK, Peña-Martínez V. Current applications of mesenchymal stem cells for cartilage tissue engineering: InTech Open; 2017. https://doi.org/10.5772/intechopen.68172.

  27. Marion NW, Mao JJ. Mesenchymal stem cells and tissue engineering. Methods Enzymol. 2006;420:339–61.

    CAS  Google Scholar 

  28. Wang H, Li Y, Zuo Y, Li J, Ma S, Cheng L. Biocompatibility and osteogenesis of biomimetic nano-hydroxyapatite/polyamide composite scaffolds for bone tissue engineering. Biomaterials. 2007;28:3338–48.

    CAS  Google Scholar 

  29. Huang AH, Farrell MJ, Mauck RL. Mechanics and mechanobiology of mesenchymal stem cell-based engineered cartilage. J Biomech. 2010;43:128–36.

    Google Scholar 

  30. Chiellini C, Cochet O, Negroni L, Samson M, Poggi M, Ailhaud G, et al. Characterization of human mesenchymal stem cell secretome at early steps of adipocyte and osteoblast differentiation. BMC Mol Biol. 2008;9:26.

    Google Scholar 

  31. Zhang F, Zhang N, Meng H-X, Liu H-X, Lu Y-Q, Liu C-M, et al. Easy applied gelatin-based hydrogel system for long-term functional cardiomyocyte culture and myocardium formation. ACS Biomater Sci Eng American Chemical Society. 2019;5:3022–31.

    CAS  Google Scholar 

  32. Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci National Academy of Sciences. 2003;100:8407–11.

    CAS  Google Scholar 

  33. Marquardt LM, Heilshorn SC. Design of injectable materials to improve stem cell transplantation. Curr Stem Cell Rep. 2016;2:207–20.

    Google Scholar 

  34. Blocki A, Beyer S, Dewavrin J-Y, Goralczyk A, Wang Y, Peh P, et al. Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium. Biomaterials. 2015;53:12–24.

    CAS  Google Scholar 

  35. Colvin RB, Smith RN. Antibody-mediated organ-allograft rejection. Nat Rev Immunol Nature Publishing Group. 2005;5:807–17.

    CAS  Google Scholar 

  36. Hummers WS, Offeman RE. Preparation of graphitic oxide. J Am Chem Soc. 1958;80:1339.

    CAS  Google Scholar 

  37. Arnold AM, Crytzer KR, Holt BD, Sydlik SA. Functional graphenic materials that seal condenser tube leaks in situ. ACS Appl Mater Interfaces. 2019;11:20881–7.

    CAS  Google Scholar 

  38. Plachá D, Jampilek J. Graphenic materials for biomedical applications. Nanomaterials. 2019;9:1758.

    Google Scholar 

  39. Saberi A, Jabbari F, Zarrintaj P, Saeb MR, Mozafari M. Electrically conductive materials: opportunities and challenges in tissue engineering. Biomolecules. 2019;9. https://doi.org/10.3390/biom9090448.

  40. Lee WC, Lim CHYX, Shi H, Tang LAL, Wang Y, Lim CT, et al. Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS Nano. 2011;5:7334–41.

    CAS  Google Scholar 

  41. Kim J, Choi KS, Kim Y, Lim K-T, Seonwoo H, Park Y, et al. Bioactive effects of graphene oxide cell culture substratum on structure and function of human adipose-derived stem cells. J Biomed Mater Res A. 2013;101:3520–30.

    Google Scholar 

  42. Chen GY, Pang DWP, Hwang SM, Tuan HY, Hu Y-C. A graphene-based platform for induced pluripotent stem cells culture and differentiation. Biomaterials. 2012;33:418–27.

    Google Scholar 

  43. Kim J, Kim HD, Park J, Lee E, Kim E, Lee SS, et al. Enhanced osteogenic commitment of murine mesenchymal stem cells on graphene oxide substrate. Biomater Res. 2018;22:1.

    Google Scholar 

  44. Holt BD, Arnold AM, Sydlik SA. In it for the long haul: the cytocompatibility of aged graphene oxide and its degradation products. Adv Healthc Mater. 2016;5:3056–66.

    CAS  Google Scholar 

  45. Yang J-W, Hsieh KY, Kumar PV, Cheng S-J, Lin Y-R, Shen Y-C, et al. Enhanced osteogenic differentiation of stem cells on phase-engineered graphene oxide. ACS Appl Mater Interfaces American Chemical Society. 2018;10:12497–503.

    CAS  Google Scholar 

  46. Kumar S, Chatterjee K. Comprehensive review on the use of Graphene-based substrates for regenerative medicine and biomedical devices. ACS Appl Mater Interfaces. 2016;8:26431–57.

    CAS  Google Scholar 

  47. La W-G, Park S, Yoon H-H, Jeong G-J, Lee T-J, Bhang SH, et al. Delivery of a therapeutic protein for bone regeneration from a substrate coated with graphene oxide. Small. 2013;9:4051–60.

    CAS  Google Scholar 

  48. La W-G, Jung M-J, Yoon J-K, Bhang SH, Jang H-K, Lee T-J, et al. Bone morphogenetic protein-2 for bone regeneration—dose reduction through graphene oxide-based delivery. Carbon. 2014;78:428–38.

    CAS  Google Scholar 

  49. Kavitha T, Kang I-K, Park S-Y. Poly(acrylic acid)-grafted graphene oxide as an intracellular protein carrier. Langmuir. 2014;30:402–9.

    CAS  Google Scholar 

  50. Chong Y, Ge C, Yang Z, Garate JA, Gu Z, Weber JK, et al. Reduced cytotoxicity of graphene nanosheets mediated by blood-protein coating. ACS Nano. 2015;9:5713–24.

    CAS  Google Scholar 

  51. Ebrahimi S, Montazeri A, Rafii-Tabar H. Molecular dynamics study of the interfacial mechanical properties of the graphene–collagen biological nanocomposite. Comput Mater Sci. 2013;69:29–39.

    CAS  Google Scholar 

  52. Podila R, Vedantam P, Ke PC, Brown JM, Rao AM. Evidence for charge-transfer-induced conformational changes in carbon nanostructure–protein Corona. J Phys Chem C. 2012;116:22098–103.

    CAS  Google Scholar 

  53. Kumar S, Parekh SH. Linking graphene-based material physicochemical properties with molecular adsorption, structure and cell fate. Commun Chem. 2020;3:8.

    CAS  Google Scholar 

  54. Shen H, Liu M, He H, Zhang L, Huang J, Chong Y, et al. PEGylated Graphene oxide-mediated protein delivery for cell function regulation. ACS Appl Mater Interfaces American Chemical Society. 2012;4:6317–23.

    CAS  Google Scholar 

  55. Shi X, Chang H, Chen S, Lai C, Khademhosseini A, Wu H. Regulating cellular behavior on few-layer reduced graphene oxide films with well-controlled reduction states. Adv Funct Mater. 2012;22:751–9.

    CAS  Google Scholar 

  56. Baweja L, Balamurugan K, Subramanian V, Dhawan A. Effect of graphene oxide on the conformational transitions of amyloid beta peptide: a molecular dynamics simulation study. J Mol Graph Model. 2015;61:175–85.

    CAS  Google Scholar 

  57. Wu R, Wang Y, Chen L, Huang L, Chen Y. Control of the oxidation level of graphene oxide for high efficiency polymer solar cells. RSC Adv The Royal Society of Chemistry. 2015;5:49182–7.

    CAS  Google Scholar 

  58. Pandit S, De M. Roles of edges and surfaces of Graphene oxide in molecular recognition of proteins: implications for enzymatic inhibition of α-chymotrypsin. ACS Appl Nano Mater. 2020;3:3829–38.

    CAS  Google Scholar 

  59. Hong J, Shah NJ, Drake AC, DeMuth PC, Lee JB, Chen J, et al. Graphene multilayers as gates for multi-week sequential release of proteins from surfaces. ACS Nano American Chemical Society. 2012;6:81–8.

    CAS  Google Scholar 

  60. Chang Y, Yang S-T, Liu J-H, Dong E, Wang Y, Cao A, et al. In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol Lett. 2011;200:201–10.

    CAS  Google Scholar 

  61. Hu W, Peng C, Lv M, Li X, Zhang Y, Chen N, et al. Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano. 2011;5:3693–700.

    CAS  Google Scholar 

  62. Phogat N, Kohl M, Uddin I, Jahan A. Interaction of nanoparticles with biomolecules, protein, enzymes, and its applications. In: Deigner HP, Kohl M, editors. Precision Medicine: Tools and Quantitative Approaches: Academic Press; 2018. p. 253–76.

  63. Guo Y, Lu X, Weng J, Leng Y. Density functional theory study of the interaction of arginine-glycine-aspartic acid with graphene, defective graphene, and graphene oxide. J Phys Chem C. 2013;117:5708–17.

    CAS  Google Scholar 

  64. Sengupta B, Gregory WE, Zhu J, Dasetty S, Karakaya M, Brown JM, et al. Influence of carbon nanomaterial defects on the formation of protein corona. RSC Adv. 2015;5:82395–402.

    CAS  Google Scholar 

  65. Fu C, Yang X, Tan S, Song L. Enhancing cell proliferation and osteogenic differentiation of MC3T3-E1 pre-osteoblasts by BMP-2 delivery in graphene oxide-incorporated PLGA/HA biodegradable microcarriers. Sci Rep. 2017;7:12549.

    Google Scholar 

  66. La W-G, Jin M, Park S, Yoon H-H, Jeong G-J, Bhang SH, et al. Delivery of bone morphogenetic protein-2 and substance P using graphene oxide for bone regeneration. Int J Nanomedicine. 2014;9:107–16.

    Google Scholar 

  67. Weaver CL, Cui XT. Directed neural stem cell differentiation with a functionalized graphene oxide nanocomposite. Adv Healthc Mater. 2015;4:1408–16.

    CAS  Google Scholar 

  68. Liu M, Ni K, Zheng J. Interferon-γ pretreated human MSC show improved efficiency in humanized mice model of pulmonary fibrosis. Eur Respir J. 2016;48. https://doi.org/10.1183/13993003.congress-2016.PA782

  69. Liang C, Jiang E, Yao J, Wang M, Chen S, Zhou Z, et al. Interferon-γ mediates the immunosuppression of bone marrow mesenchymal stem cells on T-lymphocytes in vitro. Hematology. 2018;23:44–9.

    CAS  Google Scholar 

  70. Emadedin M, Liastani MG, Fazeli R, Mohseni F, Moghadasali R, Mardpour S, et al. Long-term follow-up of intra-articular injection of autologous mesenchymal stem cells in patients with knee, ankle, or hip osteoarthritis. Arch Iran Med. 2015;18:336–44.

    Google Scholar 

  71. Yoon HH, Bhang SH, Kim T, Yu T, Hyeon T, Kim B-S. Dual roles of Graphene oxide in chondrogenic differentiation of adult stem cells: cell-adhesion substrate and growth factor-delivery carrier. Adv Funct Mater. 2014;24:6455–64.

    CAS  Google Scholar 

  72. Zhang W, Yang G, Wang X, Jiang L, Jiang F, Li G, et al. Magnetically controlled growth-factor-immobilized multilayer cell sheets for complex tissue regeneration. Adv Mater. 2017;29:1703795.

    Google Scholar 

  73. Jana B, Biswas A, Mohapatra S, Saha A, Ghosh S. Single functionalized graphene oxide reconstitutes kinesin mediated intracellular cargo transport and delivers multiple cytoskeleton proteins and therapeutic molecules into the cell. Chem Commun. 2014;50:11595–8.

    CAS  Google Scholar 

  74. Jana B, Mondal G, Biswas A, Chakraborty I, Saha A, Kurkute P, et al. Dual functionalized graphene oxide serves as a carrier for delivering Oligohistidine- and biotin-tagged biomolecules into cells. Macromol Biosci. 2013;13:1478–84.

    CAS  Google Scholar 

  75. Choi M, Chung J-H, Cho Y, Hong BY, Hong J. Nano-film modification of collagen hydrogels for controlled growth factor release. Chem Eng Sci. 2015;137:626–30.

    CAS  Google Scholar 

  76. Navarro M, Michiardi A, Castaño O, Planell JA. Biomaterials in orthopaedics. J R Soc Interface Royal Society. 2008;5:1137–58.

    CAS  Google Scholar 

  77. Jones LC, Frondoza C, Hungerford DS. Immunohistochemical evaluation of interface membranes from failed cemented and uncemented acetabular components. J Biomed Mater Res. 1999;48:889–98.

    CAS  Google Scholar 

  78. Corbett KL, Losina E, Nti AA, Prokopetz JJZ, Katz JN. Population-based rates of revision of primary total hip arthroplasty: a systematic review. PLoS One. 2010;5:e13520.

    Google Scholar 

  79. Li D, Zhang W, Yu X, Wang Z, Su Z, Wei G. When biomolecules meet graphene: from molecular level interactions to material design and applications. Nanoscale. 2016;8:19491–509.

    CAS  Google Scholar 

  80. Wang J, Ouyang Z, Ren Z, Li J, Zhang P, Wei G, et al. Self-assembled peptide nanofibers on graphene oxide as a novel nanohybrid for biomimetic mineralization of hydroxyapatite. Carbon. 2015;89:20–30.

    CAS  Google Scholar 

  81. Qi W, Yuan W, Yan J, Wang H. Growth and accelerated differentiation of mesenchymal stem cells on graphene oxide/poly-L-lysine composite films. J Mater Chem B The Royal Society of Chemistry. 2014;2:5461–7.

    CAS  Google Scholar 

  82. Shuai Y, Mao C, Yang M. Protein nanofibril assemblies templated by graphene oxide nanosheets accelerate early cell adhesion and induce osteogenic differentiation of human mesenchymal stem cells. ACS Appl Mater Interfaces Am Chem Soc. 2018;10:31988–97.

    CAS  Google Scholar 

  83. Raslan A, Saenz del Burgo L, Ciriza J, Luis Pedraz J. Graphene oxide and reduced graphene oxide-based scaffolds in regenerative medicine. Int J Pharm. 2020;580:119226.

    CAS  Google Scholar 

  84. Eckhart KE, Holt BD, Laurencin MG, Sydlik SA. Covalent conjugation of bioactive peptides to graphene oxide for biomedical applications. Biomater Sci. 2019;7:3876–85.

    CAS  Google Scholar 

  85. Bain JL, Culpepper BK, Reddy MS, Bellis SL. Comparing variable-length polyglutamate domains to anchor an osteoinductive collagen-mimetic peptide to diverse bone grafting materials. Int J Oral Maxillofac Implants. 2014;29:1437–45.

    Google Scholar 

  86. Gentilini C, Dong Y, May JR, Goldoni S, Clarke DE, Lee B-H, et al. Functionalized poly(γ-glutamic acid) fibrous scaffolds for tissue engineering. Adv Healthc Mater. 2012;1:308–15.

    CAS  Google Scholar 

  87. Lu H, Guo L, Kawazoe N, Tateishi T, Chen G. Effects of poly(L-lysine), poly(acrylic acid) and poly(ethylene glycol) on the adhesion, proliferation and chondrogenic differentiation of human mesenchymal stem cells. J Biomater Sci Polym Ed Taylor & Francis. 2009;20:577–89.

    CAS  Google Scholar 

  88. Li J, Zheng L, Zeng L, Zhang Y, Jiang L, Song J. RGD peptide-grafted graphene oxide as a new biomimetic nanointerface for impedance-monitoring cell behaviors. J Nanomater. 2016;2016:1–12.

    Google Scholar 

  89. Shin SR, Li Y-C, Jang H, Khoshakhlagh P, Akbari M, Nasajpour A, et al. Graphene-based materials for tissue engineering. Adv Drug Deliv Rev. 2016;105:255–74.

    CAS  Google Scholar 

  90. Li C, Hsu Y-T, Hu W-W. The regulation of osteogenesis using electroactive polypyrrole films. Polymers. 2016;8:258.

    Google Scholar 

  91. Shen J, Shi M, Yan B, Ma H, Li N, Hu Y, et al. Covalent attaching protein to graphene oxide via diimide-activated amidation. Colloids Surf B: Biointerfaces. 2010;81:434–8.

    CAS  Google Scholar 

  92. Dimiev AM. Mechanism of formation and chemical structure of graphene oxide. In: Dimiev AM, Eigler S, editors. Graphene Oxide: Fundamentals and Applications: Chichester: John Wiley & Sons, Ltd; 2016. pp. 36–84.

  93. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res Oxford Academic. 2000;28:235–42.

    CAS  Google Scholar 

  94. Scheufler C, Sebald W, Hülsmeyer M. Crystal structure of human bone morphogenetic protein-2 at 2.7 Å resolution11 Edited by R. Huber. J Mol Biol. 1999;287:103–15.

    CAS  Google Scholar 

  95. González-Domínguez JM, Gutiérrez FA, Hernández-Ferrer J, Ansón-Casaos A, Rubianes MD, Rivas G, et al. Peptide-based biomaterials. Linking L-tyrosine and poly L-tyrosine to graphene oxide nanoribbons. J Mater Chem B. 2015;3:3870–84.

    Google Scholar 

  96. Kang S, Park JB, Lee T-J, Ryu S, Bhang SH, La W-G, et al. Covalent conjugation of mechanically stiff graphene oxide flakes to three-dimensional collagen scaffolds for osteogenic differentiation of human mesenchymal stem cells. Carbon. 2015;83:162–72.

    CAS  Google Scholar 

  97. Duc D, Stoddart PR, McArthur SL, Kapsa RMI, Quigley AF, Boyd-Moss M, et al. Fabrication of a biocompatible liquid crystal graphene oxide–gold Nanorods electro- and photoactive interface for cell stimulation. Adv Healthc Mater. 2019;8:1801321.

    Google Scholar 

  98. Li H, Shi L-Y, Cui W, Lei W-W, Zhang Y-L, Diao Y-F, et al. Covalent modification of graphene as a 2D nanofiller for enhanced mechanical performance of poly(glutamate) hybrid gels. RSC Adv. 2015;5:86407–13.

    CAS  Google Scholar 

  99. Imani R, Prakash S, Vali H, Faghihi S. Polyethylene glycol and octa-arginine dual-functionalized nanographene oxide: an optimization for efficient nucleic acid delivery. Biomater Sci. 2018;6:1636–50.

    CAS  Google Scholar 

  100. Sydlik SA, Swager TM. Functional graphenic materials via a Johnson−Claisen rearrangement. Adv Funct Mater. 2013;23:1873–82.

    CAS  Google Scholar 

  101. Xu G, Chen X, Hu J, Yang P, Yang D, Wei L. Immobilization of trypsin on graphene oxide for microwave-assisted on-plate proteolysis combined with MALDI-MS analysis. Analyst. 2012;137:2757–61.

    CAS  Google Scholar 

  102. Compton OC, Dikin DA, Putz KW, Brinson LC, Nguyen ST. Electrically conductive “alkylated” graphene paper via chemical reduction of amine-functionalized graphene oxide paper. Adv Mater. 2010;22:892–6.

    CAS  Google Scholar 

  103. Yang H, Li F, Shan C, Han D, Zhang Q, Niu L, et al. Covalent functionalization of chemically converted graphene sheets via silane and its reinforcement. J Mater Chem The Royal Society of Chemistry. 2009;19:4632–8.

    CAS  Google Scholar 

  104. Guo S, Nishina Y, Bianco A, Ménard-Moyon C. A flexible method for covalent double functionalization of graphene oxide. Angew Chem. 2020;132:1558–63.

    Google Scholar 

  105. Holt BD, Arnold AM, Sydlik SA. Peptide-functionalized reduced graphene oxide as a bioactive mechanically robust tissue regeneration scaffold. Polym Int. 2017;66:1190–8.

    CAS  Google Scholar 

  106. Cha C, Shin SR, Gao X, Annabi N, Dokmeci MR, Tang X(S), et al. Controlling mechanical properties of cell-laden hydrogels by covalent incorporation of graphene oxide. Small. 2014;10:514–23.

    CAS  Google Scholar 

  107. Shi L, Wang L, Chen J, Chen J, Ren L, Shi X, et al. Modifying graphene oxide with short peptide via click chemistry for biomedical applications. Appl Mater Today. 2016;5:111–7.

    Google Scholar 

  108. Hsieh T-Y, Huang W-C, Kang Y-D, Chu C-Y, Liao W-L, Chen Y-Y, et al. Neurotensin-conjugated reduced graphene oxide with multi-stage near-infrared-triggered synergic targeted neuron gene transfection in vitro and in vivo for neurodegenerative disease therapy. Adv Healthc Mater. 2016;5:3016–26.

    CAS  Google Scholar 

  109. Zou Y, Qazvini NT, Zane K, Sadati M, Wei Q, Liao J, et al. Gelatin-derived graphene–silicate hybrid materials are biocompatible and synergistically promote BMP9-induced osteogenic differentiation of mesenchymal stem cells. ACS Appl Mater Interfaces. 2017;9:15922–32.

    CAS  Google Scholar 

  110. Scheufler C, Sebald W. Human bone morphogenetic protein-2 (BMP-2) [Internet]. Protein Data Bank. Available from: https://www.rcsb.org/structure/3BMP. Accessed 2020-05-26

  111. Ligorio C, Zhou M, Wychowaniec JK, Zhu X, Bartlam C, Miller AF, et al. Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications. Acta Biomater. 2019;92:92–103.

    CAS  Google Scholar 

  112. Luo Y, Shen H, Fang Y, Cao Y, Huang J, Zhang M, et al. Enhanced proliferation and osteogenic differentiation of mesenchymal stem cells on graphene oxide-incorporated electrospun poly(lactic- co -glycolic acid) nanofibrous mats. ACS Appl Mater Interfaces. 2015;7:6331–9.

    CAS  Google Scholar 

  113. Jiang Y, Xu Z, Huang T, Liu Y, Guo F, Xi J, et al. Direct 3D printing of ultralight graphene oxide aerogel microlattices. Adv Funct Mater. 2018;28:1707024.

    Google Scholar 

  114. Choe G, Oh S, Seok JM, Park SA, Lee JY. Graphene oxide/alginate composites as novel bioinks for three-dimensional mesenchymal stem cell printing and bone regeneration applications. Nanoscale. 2019;11:23275–85.

    CAS  Google Scholar 

  115. Hongo C, Nagarajan V, Noguchi K, Kamitori S, Okuyama K, Tanaka Y, et al. Average crystal structure of (pro-pro-Gly) 9 at 1.0Å resolution. Polym J Nature Publishing Group. 2001;33:812–8.

    CAS  Google Scholar 

  116. Arnold AM, Holt BD, Daneshmandi L, Laurencin CT, Sydlik SA. Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration. Proc Natl Acad Sci. 2019;116:4855–60.

    CAS  Google Scholar 

  117. Chu J, Shi P, Yan W, Fu J, Yang Z, He C, et al. PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing. Nanoscale The Royal Society of Chemistry. 2018;10:9547–60.

    CAS  Google Scholar 

  118. Purohit SD, Bhaskar R, Singh H, Yadav I, Gupta MK, Mishra NC. Development of a nanocomposite scaffold of gelatin–alginate–graphene oxide for bone tissue engineering. Int J Biol Macromol. 2019;133:592–602.

    CAS  Google Scholar 

  119. Freeman FE, Kelly DJ. Tuning alginate bioink stiffness and composition for controlled growth factor delivery and to spatially direct MSC fate within bioprinted tissues. Sci Rep. 2017;7:17042.

    Google Scholar 

  120. Jin S, Li K, Li J. A general bio-inspired, novel interface engineering strategy toward strong yet tough protein based composites. Appl Surf Sci. 2018;447:452–62.

    CAS  Google Scholar 

  121. Tatavarty R, Ding H, Lu G, Taylor RJ, Bi X. Synergistic acceleration in the osteogenesis of human mesenchymal stem cells by graphene oxide–calcium phosphate nanocomposites. Chem Commun. 2014;50:8484–7.

    CAS  Google Scholar 

  122. Liu S, Zhou C, Mou S, Li J, Zhou M, Zeng Y, et al. Biocompatible graphene oxide–collagen composite aerogel for enhanced stiffness and in situ bone regeneration. Mater Sci Eng C. 2019;105:110137.

    CAS  Google Scholar 

  123. Olate-Moya F, Arens L, Wilhelm M, Mateos-Timoneda MA, Engel E, Palza H. Chondroinductive alginate-based hydrogels having graphene oxide for 3D printed scaffold fabrication. ACS Appl Mater Interfaces. 2020;12:4343–57.

    CAS  Google Scholar 

  124. Park J, Lee SJ, Lee H, Park SA, Lee JY. Three dimensional cell printing with sulfated alginate for improved bone morphogenetic protein-2 delivery and osteogenesis in bone tissue engineering. Carbohydr Polym. 2018;196:217–24.

    CAS  Google Scholar 

  125. Wozney JM, Rosen V. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop Relat Res. 1998;346:26–37.

  126. Zhang W, Fu Y, Wang Z. Fabrication and application of novel porous scaffold in situ-loaded graphene oxide and osteogenic peptide by cryogenic 3D printing for repairing critical-sized bone defect. Molecules. 2019;24:1669.

    CAS  Google Scholar 

  127. Aghdasi B, Montgomery SR, Daubs MD, Wang JC. A review of demineralized bone matrices for spinal fusion: the evidence for efficacy. Surgeon. 2013;11:39–48.

    CAS  Google Scholar 

  128. Bilem I, Plawinski L, Chevallier P, Ayela C, Sone ED, Laroche G, et al. The spatial patterning of RGD and BMP-2 mimetic peptides at the subcellular scale modulates human mesenchymal stem cells osteogenesis. J Biomed Mater Res A. 2018;106:959–70.

    CAS  Google Scholar 

  129. Liao J, Wu S, Li K, Fan Y, Dunne N, Li X. Peptide-modified bone repair materials: factors influencing osteogenic activity. J Biomed Mater Res A. 2019;107:1491–512.

    CAS  Google Scholar 

  130. Lin D, Jin S, Zhang F, Wang C, Wang Y, Zhou C, et al. 3D stereolithography printing of graphene oxide reinforced complex architectures. Nanotechnology. 2015;26:434003.

    Google Scholar 

  131. Zhong J, Zhou G-X, He P-G, Yang Z-H, Jia D-C. 3D printing strong and conductive geo-polymer nanocomposite structures modified by graphene oxide. Carbon. 2017;117:421–6.

    CAS  Google Scholar 

  132. Reneker DH, Chun I. Nanometre diameter fibres of polymer, produced by electrospinning. Nanotechnology. 1996;7:216–23.

    CAS  Google Scholar 

  133. Votteler M, Kluger PJ, Walles H, Schenke-Layland K. Stem cell microenvironments—unveiling the secret of how stem cell fate is defined. Macromol Biosci. 2010;10:1302–15.

    CAS  Google Scholar 

  134. Schenke-Layland K. Non-invasive multiphoton imaging of extracellular matrix structures. J Biophotonics. 2008;1:451–62.

    CAS  Google Scholar 

  135. Woo KM, Seo J, Zhang R, Ma PX. Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds. Biomaterials. 2007;28:2622–30.

    CAS  Google Scholar 

  136. Woo KM, Chen VJ, Ma PX. Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment. J Biomed Mater Res. 2003;67A:531–7.

    CAS  Google Scholar 

  137. Wahab IF, Razak SIA, Azmi NS, Dahli FN, Yusof AHM, Nayan NHM. Electrospun graphene oxide-based nanofibres. InTech Open. 2016; https://doi.org/10.5772/64055.

  138. Kim TG, Park TG. Biomimicking extracellular matrix: cell adhesive RGD peptide modified electrospun poly(D,L-lactic-co-glycolic acid) nanofiber mesh. Tissue Eng. 2006;12:221–33.

    CAS  Google Scholar 

  139. Shin YM, Jo S-Y, Park J-S, Gwon H-J, Jeong SI, Lim Y-M. Synergistic effect of dual-functionalized fibrous scaffold with BCP and RGD containing peptide for improved osteogenic differentiation: dual-functionalized fibrous scaffold for bone tissue engineering. Macromol Biosci. 2014;14:1190–8.

    CAS  Google Scholar 

  140. Shin YC, Lee JH, Jin L, Kim MJ, Kim Y-J, Hyun JK, et al. Stimulated myoblast differentiation on graphene oxide-impregnated PLGA-collagen hybrid fibre matrices. J Nanobiotechnol. 2015;13:21.

    Google Scholar 

  141. Shin YC, Kim J, Kim SE, Song S-J, Hong SW, Oh J-W, et al. RGD peptide and graphene oxide co-functionalized PLGA nanofiber scaffolds for vascular tissue engineering. Regen Biomater Oxford Academic. 2017;4:159–66.

    CAS  Google Scholar 

  142. Gaihre B, Unagolla JM, Liu J, Ebraheim NA, Jayasuriya AC. Thermoresponsive injectable microparticle–gel composites with recombinant BMP-9 and VEGF enhance bone formation in rats. ACS Biomater Sci Eng. 2019;5:4587–600.

    CAS  Google Scholar 

  143. Nair M, Nancy D, Krishnan AG, Anjusree GS, Vadukumpully S, Nair SV. Graphene oxide nanoflakes incorporated gelatin–hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells. Nanotechnology. 2015;26:161001.

    Google Scholar 

  144. Feng L, Hao Y, Zhu M, Zhai Y, Yang L, Liu Y, et al. Incorporation of laminarin-based hydrogel with graphene foam to enhance the toughness of scaffold and regulate the stem cell behavior. ACS Biomater Sci Eng. 2019;5:5295–304.

    CAS  Google Scholar 

  145. Paul A, Hasan A, Kindi HA, Gaharwar AK, Rao VTS, Nikkhah M, et al. Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair. ACS Nano American Chemical Society. 2014;8:8050–62.

    CAS  Google Scholar 

  146. Ligorio C, Zhou M, Wychowaniec JK, Zhu X, Bartlam C, Miller AF, et al. Graphene oxide containing self-assembling peptide hybrid hydrogels as a potential 3D injectable cell delivery platform for intervertebral disc repair applications. Acta Biomater. 2019;92:92–103.

    CAS  Google Scholar 

  147. Wu J, Chen A, Qin M, Huang R, Zhang G, Xue B, et al. Hierarchical construction of a mechanically stable peptide–graphene oxide hybrid hydrogel for drug delivery and pulsatile triggered release in vivo. Nanoscale The Royal Society of Chemistry. 2015;7:1655–60.

    CAS  Google Scholar 

  148. Shin SR, Zihlmann C, Akbari M, Assawes P, Cheung L, Zhang K, et al. Reduced Graphene oxide-GelMA hybrid hydrogels as scaffolds for cardiac tissue engineering. Small. 2016;12:3677–89.

    CAS  Google Scholar 

  149. Yang Q, Wang Z, Weng J. Self-assembly of natural tripeptide glutathione triggered by graphene oxide. Soft Matter The Royal Society of Chemistry. 2012;8:9855–63.

    CAS  Google Scholar 

  150. Mamaghani KR, Naghib SM, Zahedi A, Rahmanian M, Mozafari M. GelMa/PEGDA containing graphene oxide as an IPN hydrogel with superior mechanical performance. Mater Today Proc. 2018;5:15790–9.

    CAS  Google Scholar 

  151. Piao Y, Chen B. One-pot synthesis and characterization of reduced graphene oxide–gelatin nanocomposite hydrogels. RSC Adv Royal Society of Chemistry. 2016;6:6171–81.

    CAS  Google Scholar 

  152. Piao Y, Chen B. Self-assembled graphene oxide–gelatin nanocomposite hydrogels: characterization, formation mechanisms, and pH-sensitive drug release behavior. J Polym Sci Part B Polym Phys. 2015;53:356–67.

    CAS  Google Scholar 

  153. Wychowaniec JK, Iliut M, Zhou M, Moffat J, Elsawy MA, Pinheiro WA, et al. Designing peptide/graphene hybrid hydrogels through fine-tuning of molecular interactions. Biomacromolecules American Chemical Society. 2018;19:2731–41.

    CAS  Google Scholar 

  154. Shin SR, Aghaei-Ghareh-Bolagh B, Dang TT, Topkaya SN, Gao X, Yang SY, et al. Cell-laden microengineered and mechanically tunable hybrid hydrogels of gelatin and graphene oxide. Adv Mater. 2013;25:6385–91.

    CAS  Google Scholar 

  155. Fukada E, Yasuda I. On the piezoelectric effect of bone. J Phys Soc Jpn. 1957;12:1158–62.

    Google Scholar 

  156. Santhosh M, Choi J-H, Choi J-W. Magnetic-assisted cell alignment within a magnetic nanoparticle-decorated reduced graphene oxide/collagen 3D nanocomposite hydrogel. Nanomater. 2019;9:1293−306.

  157. Park J, Kim IY, Patel M, Moon HJ, Hwang S-J, Jeong B. 2D and 3D hybrid systems for enhancement of chondrogenic differentiation of tonsil-derived mesenchymal stem cells. Adv Funct Mater. 2015;25:2573–82.

    CAS  Google Scholar 

  158. Zhou M, Lozano N, Wychowaniec JK, Hodgkinson T, Richardson SM, Kostarelos K, et al. Graphene oxide: a growth factor delivery carrier to enhance chondrogenic differentiation of human mesenchymal stem cells in 3D hydrogels. Acta Biomater. 2019;96:271–80.

    CAS  Google Scholar 

  159. Patel M, Moon HJ, Ko DY, Jeong B. Composite system of graphene oxide and polypeptide thermogel as an injectable 3D scaffold for adipogenic differentiation of tonsil-derived mesenchymal stem cells. ACS Appl Mater Interfaces American Chemical Society. 2016;8:5160–9.

    CAS  Google Scholar 

  160. Girão AF, Gonçalves GS, Bhangra KB, Phillips J, Knowles J, Irurueta G, et al. Electrostatic self-assembled graphene oxide-collagen scaffolds towards a three-dimensional microenvironment for biomimetic applications. RSC Adv Royal Society of Chemistry. 2016;6:49039–51.

    Google Scholar 

  161. Olad A, Bakht Khosh Hagh H. Graphene oxide and amin-modified graphene oxide incorporated chitosan-gelatin scaffolds as promising materials for tissue engineering. Compos Part B Eng. 2019;162:692–702.

    CAS  Google Scholar 

  162. Olad A, Bakht Khosh Hagh H, Mirmohseni A, Farshi Azhar F. Graphene oxide and montmorillonite enriched natural polymeric scaffold for bone tissue engineering. Ceram Int. 2019;45:15609–19.

    CAS  Google Scholar 

  163. Rehman SR u, Augustine R, Zahid AA, Ahmed R, Tariq M, Hasan A. Reduced graphene oxide incorporated GelMA hydrogel promotes angiogenesis for wound healing applications. Int J Nanomedicine. 2019;14:9603–17.

    Google Scholar 

  164. Huang L, Li C, Yuan W, Shi G. Strong composite films with layered structures prepared by casting silk fibroin–graphene oxide hydrogels. Nanoscale Royal Society of Chemistry. 2013;5:3780–6.

    CAS  Google Scholar 

  165. Balu R, Reeder S, Knott R, Mata J, de Campo L, Dutta NK, et al. Tough Photocrosslinked silk fibroin/graphene oxide nanocomposite hydrogels. Langmuir American Chemical Society. 2018;34:9238–51.

    CAS  Google Scholar 

  166. Annabi N, Shin SR, Tamayol A, Miscuglio M, Bakooshli MA, Assmann A, et al. Highly elastic and conductive human-based protein hybrid hydrogels. Adv Mater. 2016;28:40–9.

    CAS  Google Scholar 

  167. Wang E, Desai MS, Lee S-W. Light-controlled graphene-elastin composite hydrogel actuators. Nano Lett American Chemical Society. 2013;13:2826–30.

    CAS  Google Scholar 

  168. Xing P, Chu X, Li S, Ma M, Hao A. Hybrid gels assembled from Fmoc–amino acid and graphene oxide with controllable properties. ChemPhysChem. 2014;15:2377–85.

    CAS  Google Scholar 

  169. Adhikari B, Banerjee A. Short peptide based hydrogels: incorporation of graphene into the hydrogel. Soft Matter The Royal Society of Chemistry. 2011;7:9259–66.

    CAS  Google Scholar 

  170. Iglesias D, Melle-Franco M, Kurbasic M, Melchionna M, Abrami M, Grassi M, et al. Oxidized nanocarbons-tripeptide supramolecular hydrogels: shape matters! ACS Nano American Chemical Society. 2018;12:5530–8.

    CAS  Google Scholar 

  171. Chen H, Erndt-Marino J, Diaz-Rodriguez P, Kulwatno J, Jimenez-Vergara AC, Thibeault SL, et al. In vitro evaluation of anti-fibrotic effects of select cytokines for vocal fold scar treatment. J Biomed Mater Res B Appl Biomater. 2019;107:1056–67.

    CAS  Google Scholar 

  172. Ahadian S, Naito U, Surya VJ, Darvishi S, Estili M, Liang X, et al. Fabrication of poly(ethylene glycol) hydrogels containing vertically and horizontally aligned graphene using dielectrophoresis: an experimental and modeling study. Carbon. 2017;123:460–70.

    CAS  Google Scholar 

  173. Lei W-W, Shi L-Y, Li H, Li C-X, Diao Y-F, Zhang Y-L, et al. A novel self-assembled hybrid organogel of polypeptide-based block copolymers with inclusion of polypeptide-functionalized graphene. RSC Adv The Royal Society of Chemistry. 2017;7:1471–9.

    CAS  Google Scholar 

  174. Nie W, Peng C, Zhou X, Chen L, Wang W, Zhang Y, et al. Three-dimensional porous scaffold by self-assembly of reduced graphene oxide and nano-hydroxyapatite composites for bone tissue engineering. Carbon. 2017;116:325–37.

    CAS  Google Scholar 

  175. Ko E, Cho S-W. Biomimetic polymer scaffolds to promote stem cell-mediated osteogenesis. Int J Stem Cells. 2013;6:87–91.

    CAS  Google Scholar 

  176. Gopinathan J, Noh I. Recent trends in bioinks for 3D printing. Biomater Res. 2018;22:11.

    Google Scholar 

  177. Khorshidi S, Solouk A, Mirzadeh H, Mazinani S, Lagaron JM, Sharifi S, et al. A review of key challenges of electrospun scaffolds for tissue-engineering applications. J Tissue Eng Regen Med. 2016;10:715–38.

    CAS  Google Scholar 

  178. Lee JH, Kim HW. Emerging properties of hydrogels in tissue engineering. J Tissue Eng. 2018;9:1–4.

    Google Scholar 

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Acknowledgments

The authors thank Dr. Z. Wright for original artistic contributions to Fig. 5. For contributions to literature search, we thank M. Pitts and M. Ng.

Funding

This work was funded by start-up grants from Carnegie Mellon University, the DSF Charitable Foundation, and the NSF DMR (S.A.S.) award #1905665.

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Author notes

  1. Stephen J. Schmidt, Francesca A. Starvaggi, Michelle E. Wolf and Walker M. Vickery contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA, USA

    Karoline E. Eckhart, Stephen J. Schmidt, Francesca A. Starvaggi, Michelle E. Wolf, Walker M. Vickery & Stefanie A. Sydlik

  2. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA

    Michelle E. Wolf & Stefanie A. Sydlik

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  1. Karoline E. Eckhart
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Conceptualization: Stefanie S. Sydlik; literature search, writing, and editing: Karoline E. Eckhart, Stephen J. Schmidt, Michelle E. Wolf, Walker M. Vickery, and Francesca A. Starvaggi; supervision: Karoline E. Eckhart and Stefanie S. Sydlik.

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Eckhart, K.E., Schmidt, S.J., Starvaggi, F.A. et al. Peptide- and Protein-Graphene Oxide Conjugate Materials for Controlling Mesenchymal Stem Cell Fate. Regen. Eng. Transl. Med. 7, 460–484 (2021). https://doi.org/10.1007/s40883-020-00182-y

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