Abstract
Reactive oxygen species (ROS) are important in regulating normal cell physiological functions, i.e., cell death, proliferation and differentiation. Redox modulation could have significant implications providing an opportunity for the development of new strategies to improve clinical therapeutic outcomes in the treatment of diabetes, hypertension, atherosclerosis, carcinogenesis, aging and infections. Here, we report a versatile synthetic method to produce three polyethylene glycol (PEG)-based nanocomposite hydrogels containing different graphene derivatives homogeneously distributed: graphene oxide (GO), reduced graphene oxide (rGO) and graphene nanoplatelets (GNP) by free-radical redox polymerization. The graphene–PEG nanocomposite hydrogels (GCH) were very stable at different pH and solvents. Incorporation of small amount (1% wt) of graphene additives led to enhanced mechanical properties, up to 2.5-fold increase in elastic modulus and higher thermal stability (53–62 °C). The swelling behavior strongly depended on the functionalization of the graphene additive and their interaction with PEG. Interestingly, incorporation of graphene additives conferred antioxidant/pro-oxidant activity to the hydrogel, with their radical scavenging activity depending on the nature of the radical and the graphene derivative. PEG-rGO and PEG-GNP showed the highest scavenging activity for 2,2-Diphenyl-1-picrylhydrazyl radical (DPPH•) and hydroxyl radical, respectively. In addition, PEG-rGO demonstrated peroxidase activity in the presence of H2O2. The three GCH proved biocompatible, with no effect on cell viability and proliferation of human bone marrow derived mesenchymal stem cells (hMSC). The results pave the way for the design of bioactive functional nanocomposite hydrogels for ROS-mediated applications.
Graphical abstract
Similar content being viewed by others
References
Idelchik MDPS, Begley U, Begley TJ, Melendez JA (2017) Mitochondrial ROS control of cancer. Semin Cancer Biol 47:57–66. https://doi.org/10.1016/j.semcancer.2017.04.005
Ranneh Y, Ali F, Akim AM, Hamid HA, Khazaai H, Fadel A (2017) Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review. Appl Biol Chem 60(3):327–338. https://doi.org/10.1007/s13765-017-0285-9
Kayama Y, Raaz U, Jagger A, Adam M, Schellinger IN, Sakamoto M, Suzuki H, Toyama K, Spin JM, Tsao PS (2015) Diabetic cardiovascular disease induced by oxidative stress. Int J Mol Sci 16:25234–25263. https://doi.org/10.3390/ijms161025234
Bala A, Mondal C, Haldar PK, Khandelwal B (2017) Oxidative stress in inflammatory cells of patient with rheumatoid arthritis: clinical efficacy of dietary antioxidants. Inflammopharmacology 25:595–607. https://doi.org/10.1007/s10787-017-0397-1
Di Pietro M, Filardo S, Falasca F, Turriziani O, Sessa R (2017) Infectious agents in atherosclerotic cardiovascular diseases through oxidative stress. Int J Mol Sci 18:2459–2473. https://doi.org/10.3390/ijms18112459
Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795. https://doi.org/10.1038/nature05292
Mouthuy PA, Snelling SJB, Dakin SG, Milkovic L, Gasparovic AC, Carr AJ, Zarkovic N (2016) Biocompatibility of implantable materials: an oxidative stress viewpoint. Biomaterials 109:55–68. https://doi.org/10.1016/j.biomaterials.2016.09.010
Brieger K, Schiavone S, Miller FJ Jr, Krause KH (2012) Reactive oxygen species: from health to disease. Swiss Med Wkly. https://doi.org/10.4414/smw.2012.13659
Alfadda AA, Sallam RM (2012) Reactive oxygen species in health and disease. J Biomed Biotechnol. https://doi.org/10.1155/2012/936486
Manda G, Nechifor MT, Neagu TM (2009) Reactive oxygen species, cancer and anti-cancer therapies. Curr Chem Biol 3:342–366. https://doi.org/10.2174/2212796810903010022
Topaloglu N, Guney M, Aysan N, Gulsoy M, Yuksel S (2016) The role of reactive oxygen species in the antibacterial photodynamic treatment: photoinactivation vs proliferation. Lett Appl Microbiol 62:230–236. https://doi.org/10.1111/lam.12538
Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J (2000) Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng 2:9–29. https://doi.org/10.1146/annurev.bioeng.2.1.9
Deligkaris K, Tadele TS, Olthuis W, van den Berg A (2010) Hydrogel-based devices for biomedical applications. Sensor Actuat B-Chem 147:765–774. https://doi.org/10.1016/j.snb.2010.03.083
Palmieri V, Papi M, Conti C, Ciasca G, Maulucci G, De Spirito M (2016) The future development of bacteria fighting medical devices: the role of graphene oxide. Expert Rev Med Devices 13:1013–1019. https://doi.org/10.1080/17434440.2016.1245612
Ghawanmeh AA, Ali GAM, Algarni H, Sarkar SM, Chong KF (2019) Graphene oxide-based hydrogels as a nanocarrier for anticancer drug delivery. Nano Res 12:973–990. https://doi.org/10.1007/s12274-019-2300-4
Asadi N, Alizadeh E, Salehi R, Khalandi B, Davaran S, Akbarzadeh A (2017) Nanocomposite hydrogels for cartilage tissue engineering: a review. Artif Cells Nanomed Biotechnol 46:465–471. https://doi.org/10.1080/21691401.2017.1345924
Liu W, Zhang X, Zhou L, Shang L, Su Z (2019) Reduced graphene oxide (rGO) hybridized hydrogel as a near-infrared (NIR)/pH dual-responsive platform for combined chemo-photothermal therapy. J Colloid Interf Sci 536:160–170. https://doi.org/10.1016/j.jcis.2018.10.050
Song HS, Kwon OS, Kim JH, Conde J, Artzi N (2017) 3D hydrogel scaffold doped with 2D graphene materials for biosensors and bioelectronics. Biosens Bioelectron 89:187–200. https://doi.org/10.1016/j.bios.2016.03.045
Song H, Zhang X, Liu Y, Su Z (2019) Developing graphene-based nanohybrids for electrochemical sensing. Chem Rec 19:534–549. https://doi.org/10.1002/tcr.201800084
Goeun C, Seon-Wook K, Junggeon P, Junha P, Semin K, Sook KY, Youngkeun A, Da-Woon J, Darren WR, Young LJ (2019) Anti-oxidant activity reinforced reduced graphene oxide/alginate microgels: Mesenchymal stem cell encapsulation and regeneration of infarcted hearts. Biomaterials 225:119513. https://doi.org/10.1016/j.biomaterials.2019.119513
Christensen IL, Sun Y-P, Juzenas P (2011) Carbon dots as antioxidants and prooxidants. J Biomed Nanotechnol 7:667–676. https://doi.org/10.1166/jbn.2011.1334
Qiu Y, Wang Z, Owens ACE, Kulaots I, Chen Y, Kane AB, Hurt RH (2014) Antioxidant chemistry of graphene-based materials and its role in oxidation protection technology. Nanoscale 6:11744–11755. https://doi.org/10.1039/C4NR03275F
Martin C, Merino S, Gonzalez-Dominguez JM, Vazquez E, Prato M, Rauti R, Ballerini L (2017) Graphene improves the biocompatibility of polyacrylamide hydrogels: 3D polymeric scaffolds for neuronal growth. Sci Rep 7:10942. https://doi.org/10.1038/s41598-017-11359-x
Jokerst JV, Lobovkina T, Zare RN, Gambhir SS (2011) Nanoparticle PEGylation for imaging and therapy. Nanomedicine 6:715–728. https://doi.org/10.2217/nnm.11.19
Guo Y, Duan B, Cui L, Zhu P (2015) Construction of chitin/graphene oxide hybrid hydrogels. Cellulose 22:2035–2043. https://doi.org/10.1007/s10570-015-0630-2
Cong HP, Wang P, Yu SH (2013) Stretchable and self-healing graphene oxide-polymer composite hydrogels: a dual-network design. Chem Mater 25:3357–3362. https://doi.org/10.1021/cm401919c
Díez-Pascual AM, Díez-Vicente AL (2016) Poly(propylene fumarate)/polyethylene glycol-modified graphene oxide nanocomposites for tissue engineering. ACS Appl Mater Inter 8:17902–17914. https://doi.org/10.1021/acsami.6b05635
Potts JR, Dreyer DR, Bielawski CW, Ruoff RS (2011) Graphene-based polymer nanonanocomposites. Polymer 52:5–25. https://doi.org/10.1016/j.polymer.2010.11.042
Wan C, Chen B (2012) Reinforcement and interphase of polymer/graphene oxide nanonanocomposites. J Mater Chem 22:3637–3646. https://doi.org/10.1039/C2JM15062J
Zhao S, Lan M, Zhu X, Xue H, Ng T-W, Meng X, Lee C-S, Wang P, Zhang W (2015) Green synthesis of bifunctional fluorescent carbon dots from garlic for cellular imaging and free radical scavenging. ACS Appl Mater Interf 7:17054–17060. https://doi.org/10.1021/acsami.5b03228
Blois MS (1958) Antioxidant determinations by the use of a stable free radical. Nature 181:1199–1200. https://doi.org/10.1038/1811199a0
Garg B, Bisht T, Ling YC (2015) Graphene-based nanomaterials as efficient peroxidase mimetic catalysts for biosensing applications: an overview. Molecules 20:14155–14190. https://doi.org/10.3390/molecules200814155
Chong Y, Ge C, Fang G, Tian X, Ma X, Wen T, Wamer WG, Chen C, Chai Z, Yin J-J (2016) Crossover between anti- and pro-oxidant activities of graphene quantum dots in the absence or presence of light. ACS Nano 10:8690–8699. https://doi.org/10.1021/acsnano.6b04061
Park J, Kim IY, Patel M, Moon HJ, Hwang SJ, Jeong B (2015) 2D and 3D hybrid systems for enhancement of chondrogenic differentiation of tonsil-derived mesenchymal stem cells. Adv Funct Mater 25:2573–2582. https://doi.org/10.1002/adfm.201500299
Acknowledgements
Ms. Eider Begiristain is acknowledged for her precious help in the experimental work.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Laura Sánchez-Abella, Virginia Ruiz, Adrián Pérez-San Vicente, Hans-Jürgen Grande, Iraida Loinaz and Damien Dupin declare that they have no conflict of interest.
Additional information
Handling Editor: Maude Jimenez.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sánchez-Abella, L., Ruiz, V., Pérez-San Vicente, A. et al. Reactive oxygen species (ROS)-responsive biocompatible polyethylene glycol nanocomposite hydrogels with different graphene derivatives. J Mater Sci 56, 10041–10052 (2021). https://doi.org/10.1007/s10853-021-05919-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10853-021-05919-w