Oral and maxillofacial tumors, trauma and infections are the main causes of jaw defects, whose clinical treatment is very complicated. With the development of biological tissue engineering, many biological materials have been widely used in various fields of stomatology, and they play a very important role in the repair and replacement of maxillofacial bone defects. In this study, we intended to prepare a graphene oxide/hyaluronic acid/chitosan (GO/HA/CS) composite hydrogel with different mass ratios of GO: 0.1% (0.1% GO/HA/CS), 0.25% (0.25% GO/HA/CS), 0.5% (0.5% GO/HA/CS), and 1% (1% GO/HA/CS), prepare it into a multilayered and stable composite scaffold through 3D-printing technology, observe the surface morphology of the composite scaffold through scanning electron microscopy (SEM), and then test its physical and chemical properties, mechanical properties, water swelling rate, in vitro degradation and other material properties. Moreover, the biological performance of the GO/HA/CS composite scaffold was studied through experiments, such as cell morphology observation, cell adhesion, cell proliferation, and live-dead cell staining. The results showed that through chemical cross-linking and 3D-printing technology, a porous (pore size: 450–580 μm) and multilayered GO/HA/CS biological scaffold could be successfully constructed, and its surface was an interconnected microporous structure, and the porosity decreased (94%−40%) gradually with the increase of GO. Meanwhile, with the change in GO concentration, some mechanical properties of the scaffold could be improved, such as water swelling rate, degradation rate, and elastic modulus. In addition, the composite scaffold with the appropriate amount of GO had almost no cytotoxicity and could promote cell growth and proliferation, especially 0.25% GO/HA/CS composite scaffold. Consequently, the 0.25% GO/HA/CS composite scaffold had excellent biological material properties and good biocompatibility with osteoblasts, which may provide a new idea for the repair of jaw defects.
SongYWJungHAnY, et al. Addition of autogenous bone chips to deproteinized bovine bone mineral does not have additional benefit in lateral ridge augmentation—a preclinical in vivo experimental study. Clin Oral Implants Res2021; 32(9): 1105–1114.
2.
WangQHuangZHuangX, et al. Reparative effect of super active platelet combined with allogeneic bone for large bone defects. Artif Organs2021; 45(10): 1219–1228.
3.
WanMLiuSHuangD, et al. Biocompatible heterogeneous bone incorporated with polymeric biocomposites for human bone repair by 3D printing technology. J Appl Polym Sci2021; 138(13): 50114.
4.
RosetiLParisiVPetrettaM, et al. Scaffolds for bone tissue engineering: state of the art and new perspectives. Mater Sci Eng C Mater Biol Appl2017; 78(12): 1246–1262.
5.
AmiryaghoubiNFathiMPesyanNN, et al. Bioactive polymeric scaffolds for osteogenic repair and bone regenerative medicine. Med Res Rev2020; 40(5): 1833–1870.
6.
WanXLiPJinX, et al. Poly(ε-caprolactone)/keratin/heparin/VEGF biocomposite mats for vascular tissue engineering. J Biomed Mater Res A2020; 108(2): 292–300.
7.
SchnaußJSchmidtBUSBrazelCB, et al. Influence of hyaluronic acid binding on the actin cortex measured by optical forces. J Biophotonics2020; 13(7): e201960215.
8.
GilarskaALewandowska-łańcuckaJGuzdek-ZającK, et al. Bioactive yet antimicrobial structurally stable collagen/chitosan/lysine functionalized hyaluronic acid - based injectable hydrogels for potential bone tissue engineering applications. Int J Biol Macromol2020; 155(3): 938–950.
9.
MurugesanSScheibelT. Chitosan-based nanocomposites for medical applications. J Polym Sci2021; 59(15): 1610–1642.
10.
SorienteAFasolinoIGomez-SánchezA, et al. Chitosan/hydroxyapatite nanocomposite scaffolds to modulate osteogenic and inflammatory response. J Biomed Mater Res A2022; 110(2): 266–272.
11.
KrishnaASRadhakumaryCSreenivasanK. Calcium ion modulates protein release from chitosan-hyaluronic acid poly electrolyte gel. Polym Eng Sci2015; 55(9): 2089–2097.
12.
NathSDAbuevaCKimB, et al. Chitosan-hyaluronic acid polyelectrolyte complex scaffold crosslinked with genipin for immobilization and controlled release of BMP-2. Carbohydr Polym2015; 115(12): 160–169.
13.
SantosASOliveiraTCRodriguesKF, et al. Amino-functionalized carbon nanotubes for effectively improving the mechanical properties of pre-impregnated epoxy resin/carbon fiber. J Appl Polym Sci2021; 138(46): 1–18.
14.
PatelDKDuttaSDGangulyK, et al. Enhanced osteogenic potential of unzipped carbon nanotubes for tissue engineering. J Biomed Mater Res A2021; 109(10): 1869–1880.
15.
AmiryaghoubiNFathiMBarzegariA, et al. Recent advances in polymeric scaffolds containing carbon nanotube and graphene oxide for cartilage and bone regeneration. Mater Today Commun2021; 26(2): 102097.
16.
ZhaoXZhouMPengQ, et al. Mechanical properties improvement in highly and aligned dispersed graphene oxide/bismaleimide nanocomposites based on graphene oxide sponge. Adv Eng Mater2020; 22(8): 2000231.
17.
HongruiJXuewenLYongbinS, et al. Effect of fine-grained AZ91D coating with graphene oxide/hydroxyapatite on biocompatibility. ChemistrySelect2020; 5(26): 7768–7774.
18.
ShuaiCFengPGaoC, et al. Graphene oxide reinforced poly(vinyl alcohol): nanocomposite scaffolds for tissue engineering applications. RSC Adv2015; 5(32): 25416–25423.
19.
ZhangCWangLZhaiT, et al. The surface grafting of graphene oxide with poly(ethylene glycol) as a reinforcement for poly(lactic acid) nanocomposite scaffolds for potential tissue engineering applications. J Mech Behav Biomed Mater2016; 53(12): 403–413.
20.
WuJZhengALiuY, et al. Enhanced bone regeneration of the silk fibroin electrospun scaffolds through the modification of the graphene oxide functionalized by BMP-2 peptide. Int J Nanomedicine2019; 14(5): 733–751.
21.
XieCLuXHanL, et al. Biomimetic mineralized hierarchical graphene oxide/chitosan scaffolds with adsorbability for immobilization of nanoparticles for biomedical applications. ACS Appl Mater Interfaces2016; 8(3): 1707–1717.
22.
YangYZhangQXuT, et al. Photocrosslinkable nanocomposite ink for printing strong, biodegradable and bioactive bone graft. Biomaterials2020; 263(11): 120378.
23.
ChaudhuriOCooper-WhiteJJanmeyPA, et al. Effects of extracellular matrix viscoelasticity on cellular behaviour. Nature2020; 584(7822): 535–546.
24.
ZhangMLiLWangM, et al. 3D printing for biological scaffolds using poly(ionic liquid)/gelatin/sodium alginate ink. Macromol Mater Eng2021; 306(7): 2100084.
25.
LuRZhangWHeY, et al. Ferric ion crosslinking-based 3D printing of a graphene oxide hydrogel and its evaluation as a bio-scaffold in tissue engineering. Biotechnol Bioeng2021; 118(2): 1006–1012.
26.
ŞekerŞElçinAEElçinYM. Autologous protein-based scaffold composed of platelet lysate and aminated hyaluronic acid. J Mater Sci Mater Med2019; 30(12): 127.
27.
WiseJ. Use of glyburide to treat gestational diabetes is linked to adverse outcomes in babies, study finds. BMJ2015; 350(14): h1709.
28.
BouleftourWBouetGGranitoRN, et al. Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone. J Cell Physiol2015; 230(3): 568–577.
29.
LiuHQiuLLiuH, et al. Effects of fiber cross-angle structures on the mechanical property of 3D printed scaffolds and performance of seeded MC3T3-E1 cells. ACS Omega2021; 6(49): 33665–33675.
30.
ChengJLiuHZhaoB, et al. MC3T3-E1 preosteoblast cell-mediated mineralization of hydroxyapatite by poly-dopamine-functionalized graphene oxide. J Bioact Compat Polym2015; 30(3): 289–301.
31.
IahnkeAOESStollLBelléAS, et al.; A.S. Gelatin capsule residue-based films crosslinked with the natural agent genipin. Packag Technol Sci2020; 33(1): 15–26.
32.
KwonMYWangCGalarragaJH, et al. Influence of hyaluronic acid modification on CD44 binding towards the design of hydrogel biomaterials. Biomaterials2019; 222(3): 119451.
33.
FankhänelBHubálkováJAnezirisCG, et al. Influencing the hydrogen porosity in aluminum casting by (re)active filter materials. Adv Eng Mater2022; 24(2): 2100579.
34.
Aslam KhanMUHaiderAAbd RazakSI, et al. Arabinoxylan/graphene-oxide/nHAp-NPs/PVA bionano composite scaffolds for fractured bone healing. J Tissue Eng Regen Med2021; 15(4): 322–335.
35.
SahaAKumarSZindaniD. Investigation of the effect of water absorption on thermomechanical and viscoelastic properties of flax-hemp-reinforced hybrid composite. Polym Compos2021; 42(9): 4497–4516.
36.
ZehraMMehmoodAYarM, et al. Development of NSAID-loaded nano-composite scaffolds for skin tissue engineering applications. J Biomed Mater Res B2020; 108(8): 3064–3075.
37.
BienekDRGiuseppettiAAOkekeUC, et al. Antimicrobial, biocompatibility, and physicochemical properties of novel adhesive methacrylate dental monomers. J Bioact Compat Polym2020; 35(2): 160–173.
38.
YeLWangJLiaoC, et al. 3D printed composite scaffolds incorporating ruthenium complex–loaded liposomes as a delivery system to prevent the proliferation of MG-63 cells. Macromol Mater Eng2019; 304(11): 1900295–1900302.
39.
JiangSYuZZhangL, et al. Effects of different aperture-sized type I collagen/silk fibroin scaffolds on the proliferation and differentiation of human dental pulp cells. Regen Biomater2021; 8(4): rbab028.
40.
KarageorgiouVKaplanD. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials2005; 26(27): 5474–5491.
41.
KeavenyTMMorganEFNieburGL, et al. Biomechanics of trabecular bone. Annu Rev Biomed Eng2001; 3(17): 307–333.
42.
CooperDMMatyasJRKatzenbergMA, et al. Comparison of microcomputed tomographic and microradiographic measurements of cortical bone porosity. Calcif Tissue Int2004; 74(5): 437–447.
43.
PanzavoltaSTorricelliPAmadoriS, et al. 3D interconnected porous biomimetic scaffolds: in vitro cell response. J Biomed Mater Res A2013; 101(12): 3560–3570.
44.
ParkJYChoiYJShimJH, et al. Development of a 3D cell printed structure as an alternative to autologs cartilage for auricular reconstruction. J Biomed Mater Res Part B Appl Biomater2017; 105(5): 1016–1028.
45.
KumarSWaniMYArranjaCT, et al. Synthesis, physicochemical and optical properties of bis-thiosemicarbazone functionalized graphene oxide. Spectrochim Acta A Mol Biomol Spectrosc2018; 188(23): 183–188.
46.
RatheeshGVenugopalJRChinappanA, et al. 3D fabrication of polymeric scaffolds for regenerative therapy. ACS Biomater Sci Eng2017; 3(7): 1175–1194.
47.
WuYLD’AmatoARYanAM, et al. Three-dimensional printing of poly(glycerol sebacate) acrylate scaffolds via digital light processing. ACS Appl Bio Mater2020; 3(11): 7575–7588.
48.
ZhangXWuKLiuX, et al. Microstructure and mechanical properties of spark plasma sintered titanium-added copper/reduced graphene oxide composites. Materialwiss Werkst2019; 50(10): 1262–1272.
49.
BaoCGuoYSongL, et al. Poly(vinyl alcohol) nanocomposites based on graphene and graphite oxide: a comparative investigation of property and mechanism. J Mater Chem2011; 21(36): 13942.
50.
PanYWuTBaoH, et al. Green fabrication of chitosan films reinforced with parallel aligned graphene oxide. Carbohydr Polym2011; 83(4): 1908–1915.
51.
CobosMGonzálezBFernándezMJ, et al. Chitosan-graphene oxide nanocomposites: effect of graphene oxide nanosheets and glycerol plasticizer on thermal and mechanical properties. J Appl Polym Sci2017; 134(30): 1–14.
52.
Ur RahmanZPompaLHaiderW. Electrochemical characterization and in-vitro bio-assessment of AZ31B and AZ91E alloys as biodegradable implant materials. J Mater Sci Mater Med2015; 26(8): 217.
53.
DarnellMYoungSGuL, et al. Substrate stress-relaxation regulates scaffold remodeling and bone formation in vivo. Adv Healthc Mater2017; 6(1): 15–21.
54.
GajendiranMChoiJKimSJ, et al. Conductive biomaterials for tissue engineering applications. J Ind Eng Chem2017; 51(15): 12–26.
55.
AlexanderCShakesheffK. Responsive polymers at the biology/materials science interface. Adv Mater Weinheim2006; 18(24): 3321–3328.
56.
JunHJAcquavivaJChiD, et al. Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme. Oncogene2012; 31(25): 3039–3050.
57.
CharrierEEPogodaKWellsRG, et al. Control of cell morphology and differentiation by substrates with independently tunable elasticity and viscous dissipation. Nat Commun2018; 9(1): 449.
58.
BarretoSGonzalez-VazquezACameronAR, et al. Identification of the mechanisms by which age alters the mechanosensitivity of mesenchymal stromal cells on substrates of differing stiffness: implications for osteogenesis and angiogenesis. Acta Biomater2017; 53(9): 59–69.
59.
AidunASafaei FiroozabadyAMoharramiM, et al. Graphene oxide incorporated polycaprolactone/chitosan/collagen electrospun scaffold: enhanced osteogenic properties for bone tissue engineering. Artif Organs2019; 43(10): E264–E281.
60.
McCallionCBurthemJRees-UnwinK, et al. Graphene in therapeutics delivery: problems, solutions and future opportunities. Eur J Pharm Biopharm2016; 104(14): 235–250.
61.
GilarskaALewandowska-łańcuckaJHorakW, et al. Collagen/chitosan/hyaluronic acid - based injectable hydrogels for tissue engineering applications - design, physicochemical and biological characterization. Colloids Surf B Biointerfaces2018; 170(8): 152–162.
62.
MohammadiSShafieiSSAsadi-EydivandM, et al. Graphene oxide-enriched poly(ε-caprolactone) electrospun nanocomposite scaffold for bone tissue engineering applications. J Bioact Compat Polym2017; 32(3): 325–342.
