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RESEARCH ARTICLE

GelMA–pectin–polyhedral silsesquioxane nanocomposites for 3D bioprinting of osteogenesis-stimulating scaffolds loaded with BMP-2

Adriana Lungu1 ,  Mihaela-Raluca Dobrișan1 ,  Alexandra Ioana Cernencu1 ,  Horia Iovu1 ,  Izabela-Cristina Stancu1* ,  Elena Olăreț1 ,  Cornel Baltă2 ,  Marcel Roșu2 ,  Alina Ciceu2 ,  Anca Hermenean2* ,  Roxana Balahura3,4 ,  Sorina Dinescu3,4
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1 Advanced Polymer Materials Group, National University of Science and Technology Politehnica Bucharest, Romania
2 Department of Experimental and Applied Biology, “Aurel Ardelean” Institute of Life Sciences, “Vasile Goldis” Western University of Arad, Arad, Romania
3 Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, Bucharest, Romania
4 Research Institute of the University of Bucharest (ICUB), University of Bucharest, Bucharest, Romania
IJB, 6571 https://doi.org/10.36922/ijb.6571
Submitted: 26 November 2024 | Accepted: 21 January 2025 | Published: 22 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Harnessing the advantage of both naturally derived polymers and nanostructured materials, the current study presents a novel multicomponent hydrogel system double-reinforced with two complementary nanofillers, specifically designed for bioprinting-based tissue engineering applications. In a bioinspired approach, cellulose nanofibrils (CNFs) and polyhedral silsesquioxanes (PSS) nanoparticles were embedded in a proteinaceous–polysaccharidic matrix. To synthesize a robust platform for 3D bioprinting, methacrylate-modified biopolymers were ultraviolet-crosslinked, ensuring optimal conditions for cell encapsulation. The nanocomposite bioinks were supplemented with bone morphogenetic protein 2 (BMP-2), a potent osteogenic factor, to enhance the osteogenic differentiation of preosteoblasts. The 3D scaffold morphology was investigated, with a focus on PSS dispersion, porosity, and geometrical properties of the constructs. Swelling studies confirmed that all hydrogel samples retained their hydrophilic nature, though a slight reduction in swelling capacity was observed upon PSS incorporation. In vitro cytocompatibility tests demonstrated the beneficial effects of CNFs and PSS on cell growth. In vivo studies further revealed that hydrogels supplemented with nanostructured fillers and BMP-2 significantly enhanced osteogenesis, both in osteogenic and non-osteogenic regions. These findings prove that growth factor-reinforced scaffolds hold great potential in addressing the challenges of biomaterial research and represent a promising strategy for hard tissue regeneration.  

Graphical abstract
Keywords
BMP-2
Hybrid printing inks
In vivo osteogenesis
Nanocomposite hydrogels
Osteogenic induction
Funding
A. Lungu acknowledges support from the BIOPRINT project (GNAC ARUT 56/2023, ID 220235515), funded by the National Program for Research of the National Association of Technical Universities. I.C. Stancu and E. Olaret acknowledge support from the Next3DBone project (PN-III-P4-PCE-2021-1240, No. PCE 88/2022). The 3D printing and nanoindentation experiments were made possible through funding from the European Regional Development Fund via the Competitiveness Operational Program 2014-2020 (Priority axis 1, ID P_36_611, MySMIS code 107066, INOVABIOMED).
Conflict of interest
The authors declare they have no competing interests.
References
  1. Lanza R, Langer R, Vacanti JP. Principles of Tissue Engineering. 5th ed. Academic Press; 2020.
  2. Tan B, Gan S, Wang X, Liu W, Li X. Applications of 3D bioprinting in tissue engineering: advantages, deficiencies, improvements, and future perspectives. J Mater Chem B. 2021;9(27):5385-5413. doi: 10.1039/D1TB00172H
  3. Fatimi A, Okoro OV, Podstawczyk D, Siminska-Stannym J, Shavandi A. Natural hydrogel-based bio-inks for 3D bioprinting in tissue engineering: a review. Gels. 2022;8(3):179. doi: 10.3390/gels8030179
  4. Swarnima A, Shreya S, Krishna BV, et al. Current developments in 3D bioprinting for tissue and organ regeneration–a review. Front Mech Eng. 2020;6: 2297-3079. doi: 10.3389/fmech.2020.589171
  5. Jang J, Park HJ, Kim SW, et al. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair. Biomater. 2017;112:264-274. doi: 10.1016/j.biomaterials.2016.10.026
  6. Keriquel V, Oliveira H, Rémy M, et al. In situ printing of mesenchymal stromal cells, by laser-assisted bioprinting, for in vivo bone regeneration applications. Sci Rep. 2017;7:1778. doi: 10.1038/s41598-017-01914-x
  7. Peloquin J, Han Y, Gall K. Printability and mechanical behavior as a function of base material, structure, and a wide range of porosities for polymer lattice structures fabricated by vat-based 3D printing. Addit Manuf. 2023;78:103892. doi: 10.1016/j.addma.2023.103892
  8. Kara Y, Kovács NK, Nagy-György P, Boros R, Molnár K. A novel method and printhead for 3D printing combined nano-/microfiber solid structures. Addit Manuf. 2023;61:103315. doi: 10.1016/j.addma.2022.103315
  9. Bisht B, Hope A, Mukherjee A, Paul MK. Advances in the fabrication of scaffold and 3D printing of biomimetic bone graft. Ann Biomed Eng. 2021;49:1128-1150. doi: 10.1007/s10439-021-02752-9
  10. Bahraminasab M. Challenges on optimization of 3D-printed bone scaffolds. Biomed Eng Online. 2020;19:69. doi: 10.1186/s12938-020-00810-2
  11. Alexa RL, Cucuruz A, Ghițulică CD, et al. 3D printable composite biomaterials based on GelMA and hydroxyapatite powders doped with cerium ions for bone tissue regeneration. Int J Mol Sci. 2022;23(3):1841. doi: 10.3390/ijms23031841
  12. Li Z, Wang Q, Liu G. A review of 3D printed bone implants. Micromachines. 2022;13(4):528. doi: 10.3390/mi13040528
  13. Alexa RL, Cucuruz A, Ghițulică CD, et al. 3D printed composite scaffolds of GelMA and hydroxyapatite nanopowders doped with Mg/Zn ions to evaluate the expression of genes and proteins of osteogenic markers. Nanomater. 2022;12(19):3420. doi: 10.3390/nano12193420
  14. Lee JM, Sing SL, Zhou M, Yeong WY. 3D bioprinting processes: a perspective on classification and terminology. Int J Bioprint. 2018;4(2):151. doi: 10.18063/IJB.v4i2.151
  15. Zhang YS, Haghiashtiani G, Hübscher T, et al. 3D extrusion bioprinting. Nat Rev Methods Primers. 2021;1:75. doi: 10.1038/s43586-021-00073-8
  16. Karvinen J, Kellomäki M. Design aspects and characterization of hydrogel-based bioinks for extrusion-based bioprinting. Bioprinting. 2023;32:e00274. doi: 10.1016/j.bprint.2023.e00274
  17. Ng WL, Shkolnikov V. Jetting-based bioprinting: process, dispense physics, and applications. Bio-des. Manuf. 2024;7:771-799. doi: 10.1007/s42242-024-00285-3
  18. Li Y, Zhang X, Zhang X, Zhang Y, Hou D. Recent progress of the vat photopolymerization technique in tissue engineering: a brief review of mechanisms, methods, materials, and applications. Polym. 2023;15(9):3940. doi: 10.3390/polym15193940
  19. Jooken S, Deschaume O, Bartic C. Nanocomposite hydrogels as functional extracellular matrices. Gels. 2023;9(2):153. doi: 10.3390/gels9020153
  20. Zhang XN, Zheng Q, Wu ZL. Recent advances in 3D printing of tough hydrogels: a review. Composites B: Eng. 2022;238:109895. doi: 10.1016/j.compositesb.2022.109895
  21. Chimene D, Kaunas R, Gaharwar AK. Hydrogel bioink reinforcement for additive manufacturing: a focused review of emerging strategies. Adv Mater. 2020;32(1):1902026. doi: 10.1002/adma.201902026
  22. Curti F, Serafim A, Olaret E, et al. Development of biocomposite alginate-cuttlebone-gelatin 3D printing inks designed for scaffolds with bone regeneration potential. Mar Drugs. 2022;20(11):670. doi: 10.3390/md20110670
  23. Curti F, Stancu IC, Voicu G, et al. Development of 3D bioactive scaffolds through 3D printing using Wollastonite– Gelatin inks. Polym. 2020;12(10):2420. doi: 10.3390/polym12102420
  24. Bhattacharyya A, Janarthanan G, Tran HN, et al. Bioink homogeneity control during 3D bioprinting of multicomponent micro/nanocomposite hydrogel for even tissue regeneration using novel twin screw extrusion system. Chem Eng J. 2021;415:128971. doi: 10.1016/j.cej.2021.128971
  25. Prince E, Kumacheva E. Design and applications of man-made biomimetic fibrillar hydrogels. Nat Rev Mater. 2019;4:99-115. doi: 10.1038/s41578-018-0077-9
  26. Cernencu AI, Lungu A, Stancu IC, et al. Bioinspired 3D printable pectin-nanocellulose ink formulations. Carbohydr Polym. 2019;220:12-21. doi: 10.1016/j.carbpol.2019.05.026
  27. Ojansivu M, Rashad A, Ahlinder A, et al. Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells. Biofabr. 2019;11(3):035010. doi: 10.1088/1758-5090/ab0692
  28. Nosrati H, Mamoory RS, Le DQS, Bünger CE. Fabrication of gelatin/hydroxyapatite/3D-graphene scaffolds by a hydrogel 3D-printing method. Mater Chem Phys. 2020; 239:122305. doi: 10.1016/j.matchemphys.2019.122305
  29. Kaya H, Arici Ş, Bulut O, Bilgili F, Ege D. CNT incorporation improves the resolution and stability of porous 3D printed PLGA/HA/CNT scaffolds for bone regeneration. Mater. 2023;18:055028. doi: 10.1088/1748-605X/acf25d
  30. Cernencu AI, Dinu AI, Dinescu S, et al. Inorganic/ biopolymers hybrid hydrogels dual crosslinked for bone tissue regeneration. Gels. 2022;8(12):762. doi: 10.3390/gels8120762
  31. Marin MM, Gifu IC, Pircalabioru GG, et al. Microbial polysaccharide-based formulation with silica nanoparticles; a new hydrogel nanocomposite for 3D printing. Gels. 2023;9(5):425. doi: 10.3390/gels9050425
  32. Cernencu AI, Vlasceanu GM, Serafim A, Pircalabioru G, Ionita M. 3D double-reinforced graphene oxide - nanocellulose biomaterial inks for tissue engineered constructs. RSC Adv. 2023;10(34):24053-24063. doi: 10.1039/d3ra02786d
  33. Martins dos Santos D, Moon JI, Kim DS, et al. Hierarchical chitin nanocrystal-based 3D printed dual-layer membranes hydrogels: a dual drug delivery nano-platform for periodontal tissue regeneration. ACS Nano. 2024;18(35):24182-24203. doi: 10.1021/acsnano.4c05558
  34. Kim N, Lee H, Han G, et al. 3D-printed functional hydrogel by DNA-induced biomineralization for accelerated diabetic wound healing. Adv Sci. 2023;10:2300816. doi: 10.1002/advs.202300816
  35. Cassimjee H, Kumar P, Choonara YE, Pillay V. Proteosaccharide combinations for tissue engineering applications. Carbohydr Polym. 2020;235:115932. doi: 10.1016/j.carbpol.2020.115932
  36. Aldana AA, Valente F, Dilley R, Doyle B. Development of 3D bioprinted GelMA-alginate hydrogels with tunable mechanical properties. Bioprint. 2021;21:e00105. doi: 10.1016/j.bprint.2020.e00105
  37. Allen NB, Abar B, Johnson L, et al. 3D-bioprinted GelMA-gelatin-hydroxyapatite osteoblast-laden composite hydrogels for bone tissue engineering. Bioprint. 2022;26:e00196. doi: 10.1016/j.bprint.2022.e00196
  38. Cernencu AI, Lungu A, Dragusin DM, et al. 3D bioprinting of biosynthetic nanocellulose-filled GelMA inks highly reliable for soft tissue-oriented constructs. Mater. 2021; 14(17):4891. doi: 10.3390/ma14174891
  39. Li Z, Li S, Yang J, et al. 3D bioprinted gelatin/gellan gum-based scaffold with double-crosslinking network for vascularized bone regeneration. Carbohydr Polym. 2022;290:119469. doi: 10.1016/j.carbpol.2022.119469
  40. Wu Z, Xie S, Kang Y, et al. Biocompatibility evaluation of a 3D-bioprinted alginate-GelMA-bacteria nanocellulose (BNC) scaffold laden with oriented-growth RSC96 cells. Mater Sci Eng C. 2021;129:112393. doi: 10.1016/j.msec.2021.112393
  41. Xu W, Molino BZ, Cheng F, et al. On low-concentration inks formulated by nanocellulose assisted with gelatin methacrylate (GelMA) for 3D printing toward wound healing application. ACS Appl Mater Interf. 2019;11(9):8838-8848. doi: 10.1021/acsami.8b21268
  42. Zhang M, Yang F, Han D, et al. 3D bioprinting of corneal decellularized extracellular matrix: GelMA composite hydrogel for corneal stroma engineering. Int J Bioprinting. 2023;9(5):774. doi: 10.18063/ijb.774
  43. Lou J, Mooney DJ. Chemical strategies to engineer hydrogels for cell culture. Nat Rev Chem. 2022;6:726-744. doi: 10.1038/s41570-022-00420-7
  44. Wang W, Guo Y, Otaigbe JU. The synthesis, characterization and biocompatibility of poly(ester urethane)/polyhedral oligomeric silesquioxane nanocomposites. Polym. 2009;50(24): 5749-5757. doi: 10.1016/j.polymer.2009.05.037
  45. Liu C, Chiang B, Lewin Mejia D, et al. Mammary fibroblasts remodel fibrillar collagen microstructure in a biomimetic nanocomposite hydrogel. Acta Biomater. 2018;83:221-232. doi: 10.1016/j.actbio.2018.11.010
  46. Liu C, Lucker K, Lucker G. POSS Nanocomposite Hydrogel for 3D Bioprinting; 2019. US20190328930A1
  47. Dudman J, Ferreira AM, Gentile P, Wang X, Dalgarno K. Microvalve bioprinting of MSC-chondrocyte co-cultures. Cells. 2021;10(12):3329. doi: 10.3390/cells10123329
  48. Li X, Liu B, Pei B, et al. Inkjet bioprinting of biomaterials. Chem Rev. 2020;120(19):10793-10833. doi: 10.1021/acs.chemrev.0c00008
  49. Ng WL, Huang X, Shkolnikov V, Suntornnond R, Yeong WY. Polyvinylpyrrolidone-based bioink: influence of bioink properties on printing performance and cell proliferation during inkjet-based bioprinting. Bio-des Manuf. 2023;6:676-690. doi: 10.1007/s42242-023-00245-3
  50. Pereira FR, Sousa A, Barrias CC, Bártolo PJ, Granja PL. A single-component hydrogel bioink for bioprinting of bioengineered 3D constructs for dermal tissue engineering. Mater Horiz. 2018;5(6):1100-1111. doi: 10.1039/C8MH00525G
  51. Lungu A, Cernencu AI, Dinescu S, et al. Nanocellulose-enriched hydrocolloid-based hydrogels designed using a Ca2+ free strategy based on citric acid. Mater Des. 2021;197:109200. doi: 10.1016/j.matdes.2020.109200
  52. Cernencu A, Lungu A, Stancu IC, Vasile E, Iovu H. Polysaccharide-based 3d printing inks supplemented with additives. UPB Sci Bull Ser B Chem Mater Sci. 2019;81(4):175-186. https://www.scientificbulletin.upb.ro/SeriaB_-_Chimie_si_ Stiinta_Materialelor.php?page=revistaonline&a=2&arh_ an=2019&arh_ser=B&arh_nr=4
  53. Heggebö J, Haasters F, Polzer, H., et al. Aged human mesenchymal stem cells: the duration of bone morphogenetic protein-2 stimulation determines induction or inhibition of osteogenic differentiation. Orthopedic Rev. 2014;6(2):5242. doi: 10.4081/or.2014.5242
  54. Park JH, Koh EB, Seo YJ, Oh HS, Byun JH. BMP-9 improves the osteogenic differentiation ability over BMP-2 through p53 signaling in vitro in human periosteum-derived cells. Int J Mol Sci. 2023;24(20):15252. doi: 10.3390/ijms242015252
  55. Wu Y, Wenger A, Golzar H, Thang X. 3D bioprinting of bicellular liver lobule-mimetic structures via microextrusion of cellulose nanocrystal-incorporated shear-thinning bioink. Sci Rep. 2020;10:20648. doi: 10.1038/s41598-020-77146-3
  56. Olăreț E, Dinescu S, Dobranici AE, et al. Osteoblast responsive biosilica-enriched gelatin microfibrillar microenvironments. Biomater Adv. 2024;161:213894. doi: 10.1016/j.bioadv.2024.213894
  57. Șelaru A, Herman H, Vlăsceanu GM, et al. Graphene–oxide porous biopolymer hybrids enhance in vitro osteogenic differentiation and promote ectopic osteogenesis in vivo. Int J Mol Sci. 2022;23(1):491. doi: 10.3390/ijms23010491
  58. Hermenean A, Codreanu A, Herman H, et al. Chitosan-graphene oxide 3D scaffolds as promising tools for bone regeneration in critical-size mouse calvarial defects. Sci Rep. 2017;7:16641. doi: 10.1038/s41598-017-16599-5
  59. Patntirapong S, Chanruangvanit C, Lavanrattanakul K, Satravaha Y. Assessment of bisphosphonate treated-osteoblast behaviors by conventional assays and a simple digital image analysis. Acta Histochem. 2021;123(1):151659. doi: 10.1016/j.acthis.2020.151659
  60. Huang D, Li R, Ren J, et al. Temporal induction of Lhx8 by optogenetic control system for efficient bone regeneration. Stem Cell Res Ther. 2021;12:339. doi: 10.1186/s13287-021-02412-8
  61. Korkeamäki JT, Rashad A, Berstad K, et al. Biomimetic highly porous nanocellulose–nanohydroxyapatite scaffolds for bone tissue engineering. Cellulose. 2024;31:1-19. doi: 10.1007/s10570-024-05732-z
  62. Șelaru A, Mocanu-Dobranici AE, Olăreț E, et al. Gelatin meshes enriched with graphene oxide and magnetic nanoparticles support and enhance the proliferation and neuronal differentiation of human adipose-derived stem cells. Int J Mol Sci. 2023;24(1):555. doi: 10.3390/ijms24010555
  63. Olăreț E, Drăgușin DM, Serafim A, et al. Electrospinning fabrication and cytocompatibility investigation of nanodiamond particles-gelatin fibrous tubular scaffolds for nerve regeneration. Polym. 2021;13(3):407. doi: 10.3390/polym13030407
  64. Shi H, Yang J, You M, Li Z, He C. Polyhedral oligomeric silsesquioxanes (POSS)-based hybrid soft gels: molecular design, material advantages, and emerging applications. ACS Mater Lett. 2020;2(4):296-316. doi: 10.1021/acsmaterialslett.9b00491
  65. Choi E, Kim D, Kang D, et al. 3D-printed gelatin methacrylate (GelMA)/silanated silica scaffold assisted by two-stage cooling system for hard tissue regeneration. Regen Biomater. 2021;8(2):rbab001. doi: 10.1093/rb/rbab001
  66. Zonderland J, Moroni L. Steering cell behavior through mechanobiology in 3D: a regenerative medicine perspective. Biomater. 2021;268:120572. doi: 10.1016/j.biomaterials.2020.120572
  67. Sahebalzamani M, Ziminska M, McCarthy HO, et al. Advancing bone tissue engineering one layer at a time: a layer-by-layer assembly approach to 3D bone scaffold materials. Biomater Sci. 2022;10(11):2734-2758. doi: 10.1039/d1bm01756j
  68. Wong SK, Yee MMF, Chin KY, Ima-Nirwana S. A review of the application of natural and synthetic scaffolds in bone regeneration. J Funct Biomater. 2023;14(5):286. doi: 10.3390/jfb14050286
  69. Soleymani S, Naghib SM. 3D and 4D printing hydroxyapatite-based scaffolds for bone tissue engineering and regeneration. Heliyon. 2023;9(9):e19363. doi: 10.1016/j.heliyon.2023.e19363
  70. Yu J, Park SA, Kim WD, et al. Current advances in 3D bioprinting technology and its applications for tissue engineering. Polym (Basel). 2020;12(12):2958. doi: 10.3390/polym12122958
  71. Park JY, Choi YJ, Shim JH, Park JH, Cho DW. Development of a 3D cell printed structure as an alternative to autologs cartilage for auricular reconstruction. J Biomed Mater Res B Appl Biomater. 2017;105(5):1016-1028. doi: 10.1002/jbm.b.33639
  72. Guillemot F, Mironov V, Nakamura M. Bioprinting is coming of age: report from the international conference on bioprinting and biofabrication in Bordeaux. Biofabrication. 2010;2(1):010201. doi: 10.1088/1758-5082/2/1/010201
  73. Kim W, Kim G. Collagen/bioceramic-based composite bioink to fabricate a porous 3D hASCs-laden structure for bone tissue regeneration. Biofabrication. 2019;12(1):015007. doi: 10.1088/1758-5090/ab436d
  74. Das S, Pati F, Choi YJ, et al. Bioprintable, cell-laden silk fibroin-gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs. Acta Biomater. 2015;11:233-246. doi: 10.1016/j.actbio.2014.09.023
  75. Im S, Choe G, Seok JM, et al. An osteogenic bioink composed of alginate, cellulose nanofibrils, and polydopamine nanoparticles for 3D bioprinting and bone tissue engineering. Int J Biol Macromol. 2022;205:520-529. doi: 10.1016/j.ijbiomac.2022.02.012
  76. Janmohammadi M, Nazemi Z, Salehi AOM, et al. Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery. Bioact Mater. 2023; 20:137-163. doi: 10.1016/j.bioactmat.2022.05.018
  77. Zhu S, Chen W, Masson A, Li YP. Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis. Cell Discov. 2024;10(1):71. doi: 10.1038/s41421-024-00689-6
  78. Kim YH, Dawson JI, Oreffo ROC, et al. Gelatin methacryloyl hydrogels for musculoskeletal tissue regeneration. Bioeng. 2022;9(7):332. doi: 10.3390/bioengineering9070332
  79. Jun L, Wenzhao W, Mingxin L, et al. Biomimetic methacrylated gelatin hydrogel loaded with bone marrow mesenchymal stem cells for bone tissue regeneration. Front Bioeng Biotechnol. 2021;9:770049. doi: 10.3389/fbioe.2021.770049
  80. Yi MH, Lee JE, Kim CB, Lee KW, Lee KH. Locally controlled diffusive release of bone morphogenetic protein-2 using micropatterned gelatin methacrylate hydrogel carriers. BioChip J. 2020;14:405-420. doi: 10.1007/s13206-020-4411-0
  81. Munarin F, Guerreiro SG, Grellier MA, et al. Pectin-based injectable biomaterials for bone tissue engineering. Biomacromol. 2011;12(3):568-577. doi: 10.1021/bm101110x
  82. Di Pietro L, Ravizza A, Vozzi G, et al. European regulatory framework for the clinical translation of bioprinted scaffolds and tissues. Biomed Sci Eng. 2020;1(1):108. doi: 10.4081/bse.2019.108

 

 

 



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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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