Effects of quercetin sustained release system on osteogenic properties of MC3T3-E1 cells

doi:10.12307/2023.017

Abstract

Abstract: BACKGROUND: Quercetin plays a significant role in promoting osteogenesis, anti-allergy, anti-inflammatory, anti-oxidation, anti-virus, lowering blood pressure, and anti-platelet aggregation, but its stability and solubility are poor, which is not conducive to the exertion and application of its efficacy.
OBJECTIVE: To prepare quercetin sustained-release nanofibers for promoting bone formation and to investigate in vitro release mechanism of quercetin sustained-release nanofibers and its effect on the osteogenic properties of MC3T3-E1 cells.
METHODS: Quercetin, bovine serum albumin, and chitosan were used as materials. The quercetin sustained-release nanofibers coated with chitosan were prepared by improved solvent removal method and electrospinning technology. The quercetin sustained-release nanofibers, polycaprolactone, and polyethylene glycol were utilized as materials. The quercetin sustained-release nanofiber scaffolds were prepared using electrospinning to characterize microscopic morphology, water contact angle, and in vitro drug release of nanofibers. Polycaprolactone/polyethylene glycol nanofiber scaffolds and quercetin sustained-release nanofibers were cocultured with MC3T3-E1 cells. The cells cultured alone were taken as blank controls. The proliferation and osteogenic differentiation abilities of the three groups were detected.
RESULTS AND CONCLUSION: (1) Transmission electron microscopy showed that quercetin sustained-release nanospheres had smooth surface and uniform diameter. The microspheres could be effectively spun into the electrospinning scaffold. Scanning electron microscopy showed that the quercetin sustained-release nanospheres were regular spheres. The nanofibers were irregularly interwoven into a network structure and formed pores of different sizes without obvious fracture. (2) The contact angle experiment showed that the water contact angle of quercetin sustained-release nanofiber group was significantly smaller than that of polycaprolactone group and polycaprolactone/polyethylene glycol group. (3) The drug content released in the first 4 days reached about 30% in the quercetin sustained-release nanofiber group. The drug release time could be maintained for about one month, and the release amount could reach 70% of the drug content. (4) Compared with the blank control group, polycaprolactone/polyethylene glycol nanofibers and quercetin sustained-release nanofibers could promote MC3T3-E1 cell proliferation, alkaline phosphatase expression, and calcium deposition. (5) It is concluded that quercetin sustained-release nanofibers have a good controlled drug release effect and can promote the proliferation and osteogenic differentiation of MC3T3-E1 cells.

Key words: quercetin, sustained drug release, nanoparticle, polycaprolactone, polyethylene glycol, electrospinning, nanofiber, osteogenic effect

CLC Number:

Ma Ziyu, Zhang Bin, Zhang Yuntao, Liu Xiaolin, Bian Zhihong, Qiao Luhui, Hou Yudong. Effects of quercetin sustained release system on osteogenic properties of MC3T3-E1 cells[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(12): 1870-1876.

Figures/Tables 9

References

[1] 刘相杰,宋科官.生物支架材料及间充质干细胞在骨组织工程中的研究与应用[J].中国组织工程研究,2018,22(10):1618-1624.
[2] KONG D, SHI Y, GAO Y, et al. Preparation of BMP-2 loaded MPEG-PCL microspheres and evaluation of their bone repair properties. Biomed Pharmacother. 2020;130:110516.
[3] INJAMURI S, RAHAMAN MN, SHEN Y, et al. Relaxin enhances bone regeneration with BMP-2-loaded hydroxyapatite microspheres. J Biomed Mater Res A. 2020;108(5):1231-1242.
[4] SONG H, ZHANG Y, ZHANG Z, et al. Hydroxyapatite/NELL-1 Nanoparticles Electrospun Fibers for Osteoinduction in Bone Tissue Engineering Application. Int J Nanomedicine. 2021;16:4321-4332.
[5] LAI K, XI Y, DU X, et al. Activation of Nell-1 in BMSC Sheet Promotes Implant Osseointegration Through Regulating Runx2/Osterix Axis. Front Cell Dev Biol. 2020;8:868.
[6] HUANG K, CHEN C, CHANG C, et al. The synergistic effects of quercetin- containing 3D-printed mesoporous calcium silicate/calcium sulfate/poly-ε-caprolactone scaffolds for the promotion of osteogenesis in mesenchymal stem cells. J Formos Med Assoc. 2021;120(8):1627-1634.
[7] HUANG Y, WANG Z, DENG L, et al. Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis. Oxid Med Cell Longev. 2020;2020:1-21.
[8] WONG SK, CHIN K, IMA-NIRWANA S. Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence. Int J Mol Sci. 2020;21(17): 6448.
[9] WANG N, WANG L, YANG J, et al. Quercetin promotes osteogenic differentiation and antioxidant responses of mouse bone mesenchymal stem cells through activation of the AMPK/SIRT1 signaling pathway. Phytother Res. 2021;35(5):2639-2650.
[10] ZHANG Q, CHANG B, ZHENG G, et al. Quercetin stimulates osteogenic differentiation of bone marrow stromal cells through miRNA-206/connexin 43 pathway. Am J Transl Res. 2020;12(5):2062-2070.
[11] ZHANG W, JIA L, ZHAO B, et al. Quercetin reverses TNFα induced osteogenic damage to human periodontal ligament stem cells by suppressing the NFκB/NLRP3 inflammasome pathway. Int J Mol Med. 2021;47(4):1-11.
[12] ANGELLOTTI G, MURGIA D, CAMPISI G, et al. Quercetin-Based Nanocomposites as a Tool to Improve Dental Disease Management. Biomedicines. 2020;8(11):504.
[13] ZHOU Y, WU Y, MA W, et al. The effect of quercetin delivery system on osteogenesis and angiogenesis under osteoporotic conditions. Journal of materials chemistry. J Mater Chem B. 2017;5(3):612-625.
[14] JÓHANNESSON G, STEFÁNSSON E, LOFTSSON T. Microspheres and nanotechnology for drug delivery. Dev Ophthalmol. 2016;55(3):93-103.
[15] DEFRATES K, MARKIEWICZ T, GALLO P, et al. Protein polymer- based nano-particles: Fabrication and medical Applications. Int J Mol Sci. 2018;19(6):1717.
[16] CHA C, JEONG JH, KONG H. Poly(ethylene glycol)-poly(lactic- co-glycolic acid) core–shell microspheres with enhanced controllability of drug encapsulation and release rate. J Biomater Sci Polym Ed. 2015; 26(13):828-840.
[17] DELDAR Y, ZARGHAMI F, PILEHVAR-SOLTANAHMADI Y, et al. Antioxidant effects of chrysin-loaded electrospun nanofibrous mats on proliferation and stemness preservation of human adipose-derived stem cells. Cell Tissue Bank. 2017;18(4):475-487.
[18] SIDDIQUI N, ASAWA S, BIRRU B, et al. PCL-Based Composite Scaffold Matrices for Tissue Engineering Applications. Mol Biotechnol. 2018; 60(7):506-532.
[19] ENGEBRETSON B, SIKAVITSAS VI. Long-term in vivo effect of PEG bone tissue engineering scaffolds. J Long Term Eff Med Implants. 2012; 22(3):211.
[20] 傅娜,罗晓丁,焦铁军,等.骨组织工程中应用的聚己内酯-聚乙二醇-聚己内酯静电纺丝支架[J].中国组织工程研究,2019,23(22): 3445-3450.
[21] 潘璐,程亭亭,徐岚.聚己内酯/聚乙二醇大孔径纳米纤维膜的制备及其在组织工程支架中的应用[J].纺织学报,2020,41(9):167-173.
[22] 彭兰兰.静电纺丝法制备PCL/PEG组织工程支架的研究[D].上海:东华大学,2009.
[23] LOBO AO, AFEWERKI S, DE PAULA MMM, et al. Electrospun nanofiber blend with improved mechanical and biological performance. Int J Nanomedicine. 2018;13:7891-7903.
[24] 王乐,惠敏,董西玲,等.缓释阿托伐他汀钙纳米纤维支架对细胞黏附增殖的影响[J].中国组织工程研究,2020,24(28):4492-4497.
[25] BHARATHALA S, KOTARKONDA LK, SINGH VP, et al. In silico and experimental studies of bovine serum albumin-encapsulated carbenoxolone nanoparticles with reduced cytotoxicity. Colloids Surf B Biointerfaces. 2021;202:111670.
[26] ARRIAGADA F, GÜNTHER G, ZABALA I, et al. Development andcharacterization offlorfenicol-loaded BSAnanoparticles ascontrolledreleasecarrier. AAPS PharmSciTech. 2019;20(5):202.
[27] ZHANG Y, DONG R, PARK Y, et al. Controlled release of NELL-1 protein from chitosan/hydroxyapatite- modified TCP particles. Int J Pharm. 2016;511(1):79-89.
[28] GIZAW M, THOMPSON J, FAGLIE A, et al. Electrospun Fibers as a Dressing Material for Drug and Biological Agent Delivery in Wound Healing Applications. Bioengineering. 2018;5(1):9.
[29] LEONÉS A, MUJICA-GARCIA A, ARRIETA MP, et al. Organic and Inorganic PCL-Based Electrospun Fibers. Polymers. 2020;12(6):1325.
[30] PAGANGA G, RICE-EVANS CA. The identification of flavonoids as glycosides in human plasma. FEBS Lett. 1997;401(1):78-82.
[31] 周宇宁.中药槲皮素应用于骨缺损修复的初步研究[D].上海:上海交通大学,2016:75.
[32] WONG RWK, RABIE ABM. Effect of quercetin on preosteoblasts and bone defects. Open Orthop J. 2008;2(1):27-32.
[33] LI B, YOSHII T, HAFEMAN AE, et al. The effects of rhBMP-2 released from biodegradable polyurethane/microsphere composite scaffolds on new bone formation in rat femora. Biomaterials. 2009;30(35):6768-6779.
[34] 关德强,于波,李欣,等.中药促进骨再生的研究进展[J].时珍国医国药,2018,29(4):956-958.
[35] 陈述祥,康乐.中药促成骨细胞增殖和分化的机制与作用[J].中国组织工程研究,2012,16(7):1299-1302.
[36] 潘慧欣,崔元璐.中药诱导骨髓间充质干细胞成软骨及成骨分化的研究进展[J].天津中医药,2018,35(10):794-797.
[37] WANG XC, ZHAO NJ, GUO C, et al. Quercetin reversed lipopolysaccharide-induced inhibition of osteoblast differentiation through the mitogenactivated protein kinase pathway in MC3T3-E1 cells. Mol Med Rep. 2014;10(6):3320-3326.
[38] PANG X, CONG Y, BAO N, et al. Quercetin Stimulates Bone Marrow Mesenchymal Stem Cell Differentiation through an Estrogen Receptor-Mediated Pathway. Biomed Res Int. 2018;2018:1-11.
[39] WEI J, ZHANG X, LI Y, et al. Novel application of bergapten and quercetin with anti-bacterial, osteogenesis-potentiating, and anti-inflammation tri-effects. Acta Biochim Biophys Sin. 2021;53(6):683-696.
[40] ZENG Y, NIKITKOVA A, ABDELSALAM H, et al. Activity of quercetin and kaemferol against Streptococcus mutans biofilm. Arch Oral Biol. 2019; 98:9-16.