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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Dimethyloxallyl Glycine-Incorporated Borosilicate Bioactive Glass Scaffolds for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects

Author(s): Xiangyun Jin, Dan Han, Jie Tao, Yinjun Huang, Zihui Zhou, Zheng Zhang*, Xin Qi* and Weitao Jia*

Volume 16, Issue 6, 2019

Page: [565 - 576] Pages: 12

DOI: 10.2174/1567201816666190611105205

Price: $65

Abstract

Background: In the field of bone tissue engineering, there has been an increasing interest in biomedical materials with both high angiogenic ability and osteogenic ability. Among various osteogenesis materials, bioactive borosilicate and borate glass scaffolds possess suitable degradation rate and mechanical strength, thus drawing many scholars’ interests and attention.

Objective: In this study, we fabricated bioactive glass scaffolds composed of borosilicate 2B6Sr using the Template-Method and incorporated Dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug possessing good angiogenic ability, to improve bone regeneration.

Methods: The in-vitro studies showed that porous borosilicate bioactive glass scaffolds released slowly, a steady amount of DMOG and stimulated the proliferation and osteogenic differentiation of human bone marrow stromal cells hBMSCs.

Results: In-vivo studies showed that the borosilicate bioactive glass scaffolds could significantly promote new bone formation and neovascularization in rats’ calvarial bone defects.

Conclusion: These results indicated that DMOG-incorporated bioactive glass scaffold is a successful compound with excellent angiogenesis-osteogenesis ability, which has favorable clinical prospects.

Keywords: Dimethyloxallyl glycine, borosilicate bioactive glass, osteogenesis, angiogenesis, bone regeneration, calvarial defects.

Graphical Abstract

[1]
Zhao, S.; Zhang, J.; Zhu, M.; Zhang, Y.; Liu, Z.; Tao, C.; Zhu, Y.; Zhang, C. Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects. Acta Biomater., 2015, 12, 270-280.
[http://dx.doi.org/10.1016/j.actbio.2014.10.015] [PMID: 25449915]
[2]
Qi, X.; Liu, Y.; Ding, Z.Y.; Cao, J.Q.; Huang, J.H.; Zhang, J.Y.; Jia, W.T.; Wang, J.; Liu, C.S.; Li, X.L. Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats. Sci. Rep., 2017, 7, 42820.
[http://dx.doi.org/10.1038/srep42820] [PMID: 28230059]
[3]
Dimitriou, R.; Jones, E.; McGonagle, D.; Giannoudis, P.V. Bone regeneration: Current concepts and future directions. BMC Med., 2011, 9, 66.
[http://dx.doi.org/10.1186/1741-7015-9-66] [PMID: 21627784]
[4]
Chen, S.H.; Lei, M.; Xie, X.H.; Zheng, L.Z.; Yao, D.; Wang, X.L.; Li, W.; Zhao, Z.; Kong, A.; Xiao, D.M.; Wang, D.P.; Pan, X.H.; Wang, Y.X.; Qin, L. PLGA/TCP composite scaffold incorporating bioactive phytomolecule icaritin for enhancement of bone defect repair in rabbits. Acta Biomater., 2013, 9(5), 6711-6722.
[http://dx.doi.org/10.1016/j.actbio.2013.01.024] [PMID: 23376238]
[5]
Smith, C.A.; Richardson, S.M.; Eagle, M.J.; Rooney, P.; Board, T.; Hoyland, J.A. The use of a novel bone allograft wash process to generate a biocompatible, mechanically stable and osteoinductive biological scaffold for use in bone tissue engineering. J. Tissue Eng. Regen. Med., 2015, 9(5), 595-604.
[http://dx.doi.org/10.1002/term.1934] [PMID: 24945627]
[6]
Dumic-Cule, I.; Pecina, M.; Jelic, M.; Jankolija, M.; Popek, I.; Grgurevic, L.; Vukicevic, S. Biological aspects of segmental bone defects management. Int. Orthop., 2015, 39(5), 1005-1011.
[http://dx.doi.org/10.1007/s00264-015-2728-4] [PMID: 25772279]
[7]
Fu, Q.; Saiz, E.; Rahaman, M.N.; Tomsia, A.P. Bioactive glass scaffolds for bone tissue engineering: State of the art and future perspectives. Mater. Sci. Eng. C, 2011, 31(7), 1245-1256.
[http://dx.doi.org/10.1016/j.msec.2011.04.022] [PMID: 21912447]
[8]
Tang, W.; Lin, D.; Yu, Y.; Niu, H.; Guo, H.; Yuan, Y.; Liu, C. Bioinspired trimodal macro/micro/nano-porous scaffolds loading rhBMP-2 for complete regeneration of critical size bone defect. Acta Biomater., 2016, 32, 309-323.
[http://dx.doi.org/10.1016/j.actbio.2015.12.006] [PMID: 26689464]
[9]
Lin, D.; Yang, K.; Tang, W.; Liu, Y.; Yuan, Y.; Liu, C. A poly(glycerol sebacate)-coated mesoporous bioactive glass scaffold with adjustable mechanical strength, degradation rate, controlled-release and cell behavior for bone tissue engineering. Colloids Surf. B Biointerfaces, 2015, 131, 1-11.
[http://dx.doi.org/10.1016/j.colsurfb.2015.04.031] [PMID: 25935647]
[10]
Gu, Y.; Wang, G.; Zhang, X.; Zhang, Y.; Zhang, C.; Liu, X.; Rahaman, M.N.; Huang, W.; Pan, H. Biodegradable borosilicate bioactive glass scaffolds with a trabecular microstructure for bone repair. Mater. Sci. Eng. C, 2014, 36, 294-300.
[http://dx.doi.org/10.1016/j.msec.2013.12.023] [PMID: 24433915]
[11]
Wang, H.; Zhao, S.; Xiao, W.; Cui, X.; Huang, W.; Rahaman, M.N.; Zhang, C.; Wang, D. Three-dimensional zinc incorporated borosilicate bioactive glass scaffolds for rodent critical-sized calvarial defects repair and regeneration. Colloids Surf. B Biointerfaces, 2015, 130, 149-156.
[http://dx.doi.org/10.1016/j.colsurfb.2015.03.053] [PMID: 25912027]
[12]
Orgaz, F.; Dzika, A.; Szycht, O.; Amat, D.; Barba, F.; Becerra, J.; Santos-Ruiz, L. Surface nitridation improves bone cell response to melt-derived bioactive silicate/borosilicate glass composite scaffolds. Acta Biomater., 2016, 29, 424-434.
[http://dx.doi.org/10.1016/j.actbio.2015.10.006] [PMID: 26441124]
[13]
Jia, W.; Lau, G.Y.; Huang, W.; Zhang, C.; Tomsia, A.P.; Fu, Q. Bioactive glass for large bone repair. Adv. Healthc. Mater., 2015, 4(18), 2842-2848.
[http://dx.doi.org/10.1002/adhm.201500447] [PMID: 26582584]
[14]
Fu, Q.; Rahaman, M.N.; Bal, B.S.; Bonewald, L.F.; Kuroki, K.; Brown, R.F. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro and in vivo biological evaluation. J. Biomed. Mater. Res. A, 2010, 95(1), 172-179.
[http://dx.doi.org/10.1002/jbm.a.32823] [PMID: 20540099]
[15]
Liu, X.; Rahaman, M.N.; Day, D.E. Conversion of melt-derived microfibrous borate (13-93B3) and silicate (45S5) bioactive glass in a simulated body fluid. J. Mater. Sci. Mater. Med., 2013, 24(3), 583-595.
[http://dx.doi.org/10.1007/s10856-012-4831-z] [PMID: 23233025]
[16]
Fu, Q.; Rahaman, M.N.; Fu, H.; Liu, X. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation. J. Biomed. Mater. Res. A, 2010, 95(1), 164-171.
[http://dx.doi.org/10.1002/jbm.a.32824] [PMID: 20544804]
[17]
Gentleman, E.; Fredholm, Y.C.; Jell, G.; Lotfibakhshaiesh, N.; O’Donnell, M.D.; Hill, R.G.; Stevens, M.M. The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro. Biomaterials, 2010, 31(14), 3949-3956.
[http://dx.doi.org/10.1016/j.biomaterials.2010.01.121] [PMID: 20170952]
[18]
Huang, W.; Day, D.E.; Kittiratanapiboon, K.; Rahaman, M.N. Kinetics and mechanisms of the conversion of silicate (45S5), borate, and borosilicate glasses to hydroxyapatite in dilute phosphate solutions. J. Mater. Sci. Mater. Med., 2006, 17(7), 583-596.
[http://dx.doi.org/10.1007/s10856-006-9220-z] [PMID: 16770542]
[19]
Zhang, Q.; Oh, J.H.; Park, C.H.; Baek, J.H.; Ryoo, H.M.; Woo, K.M. Effects of Dimethyloxalylglycine-Embedded Poly(ε-caprolactone) fiber meshes on wound healing in diabetic rats. ACS Appl. Mater. Interfaces, 2017, 9(9), 7950-7963.
[http://dx.doi.org/10.1021/acsami.6b15815] [PMID: 28211272]
[20]
Zhu, Z.H.; Song, W.Q.; Zhang, C.Q.; Yin, J.M. Dimethyloxaloylglycine increases bone repair capacity of adipose-derived stem cells in the treatment of osteonecrosis of the femoral head. Exp. Ther. Med., 2016, 12(5), 2843-2850.
[http://dx.doi.org/10.3892/etm.2016.3698] [PMID: 27882083]
[21]
Trichonas, G.; Lee, T.J.; Hoppe, G.; Au, J.; Sears, J.E. Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy in the rat 50/10 model. Invest. Ophthalmol. Vis. Sci., 2013, 54(7), 4919-4926.
[http://dx.doi.org/10.1167/iovs.13-12171] [PMID: 23761085]
[22]
Zhang, J.; Guan, J.; Qi, X.; Ding, H.; Yuan, H.; Xie, Z.; Chen, C.; Li, X.; Zhang, C.; Huang, Y. Dimethyloxaloylglycine promotes the angiogenic activity of mesenchymal stem cells derived from iPSCs via activation of the PI3K/Akt pathway for bone regeneration. Int. J. Biol. Sci., 2016, 12(6), 639-652.
[http://dx.doi.org/10.7150/ijbs.14025] [PMID: 27194942]
[23]
Schipani, E.; Maes, C.; Carmeliet, G.; Semenza, G.L. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF. J. Bone Miner. Res., 2009, 24(8), 1347-1353.
[http://dx.doi.org/10.1359/jbmr.090602] [PMID: 19558314]
[24]
Wu, C.; Zhou, Y.; Chang, J.; Xiao, Y. Delivery of dimethyloxallyl glycine in mesoporous bioactive glass scaffolds to improve angiogenesis and osteogenesis of human bone marrow stromal cells. Acta Biomater., 2013, 9(11), 9159-9168.
[http://dx.doi.org/10.1016/j.actbio.2013.06.026] [PMID: 23811216]
[25]
Jaakkola, P.; Mole, D.R.; Tian, Y.M.; Wilson, M.I.; Gielbert, J.; Gaskell, S.J.; von Kriegsheim, A.; Hebestreit, H.F.; Mukherji, M.; Schofield, C.J.; Maxwell, P.H.; Pugh, C.W.; Ratcliffe, P.J. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 2001, 292(5516), 468-472.
[http://dx.doi.org/10.1126/science.1059796] [PMID: 11292861]
[26]
Ivan, M.; Kondo, K.; Yang, H.; Kim, W.; Valiando, J.; Ohh, M.; Salic, A.; Asara, J.M.; Lane, W.S.; Kaelin, W.G. Jr HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science, 2001, 292(5516), 464-468.
[http://dx.doi.org/10.1126/science.1059817] [PMID: 11292862]
[27]
Min, Z.; Shichang, Z.; Chen, X.; Yufang, Z.; Changqing, Z. 3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and osteogenesis. Biomater. Sci., 2015, 3(8), 1236-1244.
[http://dx.doi.org/10.1039/C5BM00132C] [PMID: 26222039]
[28]
Cui, Q.; Dighe, A.S.; Irvine, J.N., Jr Combined angiogenic and osteogenic factor delivery for bone regenerative engineering. Curr. Pharm. Des., 2013, 19(19), 3374-3383.
[http://dx.doi.org/10.2174/1381612811319190004] [PMID: 23432677]
[29]
Segar, C.E.; Ogle, M.E.; Botchwey, E.A. Regulation of angiogenesis and bone regeneration with natural and synthetic small molecules. Curr. Pharm. Des., 2013, 19(19), 3403-3419.
[http://dx.doi.org/10.2174/1381612811319190007] [PMID: 23432670]
[30]
Qi, X.; Huang, Y.; Han, D.; Zhang, J.; Cao, J.; Jin, X.; Huang, J.; Li, X.; Wang, T. Three-dimensional poly (ε-caprolactone)/hydroxya-patite/collagen scaffolds incorporating bone marrow mesenchymal stem cells for the repair of bone defects. Biomed. Mater., 2016, 11(2), 025005.
[http://dx.doi.org/10.1088/1748-6041/11/2/025005] [PMID: 26964015]
[31]
Qi, X.; Pei, P.; Zhu, M.; Du, X.; Xin, C.; Zhao, S.; Li, X.; Zhu, Y. Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo. Sci. Rep., 2017, 7, 42556.
[http://dx.doi.org/10.1038/srep42556] [PMID: 28211911]
[32]
Qi, X.; Zhang, J.; Yuan, H.; Xu, Z.; Li, Q.; Niu, X.; Hu, B.; Wang, Y.; Li, X. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats. Int. J. Biol. Sci., 2016, 12(7), 836-849.
[http://dx.doi.org/10.7150/ijbs.14809] [PMID: 27313497]
[33]
Zhang, J.; Liu, X.; Li, H.; Chen, C.; Hu, B.; Niu, X.; Li, Q.; Zhao, B.; Xie, Z.; Wang, Y. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway. Stem Cell Res. Ther., 2016, 7(1), 136.
[http://dx.doi.org/10.1186/s13287-016-0391-3] [PMID: 27650895]
[34]
Lin, K.; Xia, L.; Li, H.; Jiang, X.; Pan, H.; Xu, Y.; Lu, W.W.; Zhang, Z.; Chang, J. Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics. Biomaterials, 2013, 34(38), 10028-10042.
[http://dx.doi.org/10.1016/j.biomaterials.2013.09.056] [PMID: 24095251]
[35]
Yin, W.; Qi, X.; Zhang, Y.; Sheng, J.; Xu, Z.; Tao, S.; Xie, X.; Li, X.; Zhang, C. Advantages of pure platelet-rich plasma compared with leukocyte- and platelet-rich plasma in promoting repair of bone defects. J. Transl. Med., 2016, 14, 73.
[http://dx.doi.org/10.1186/s12967-016-0825-9] [PMID: 26980293]
[36]
Wang, Y.; Wan, C.; Deng, L.; Liu, X.; Cao, X.; Gilbert, S.R.; Bouxsein, M.L.; Faugere, M.C.; Guldberg, R.E.; Gerstenfeld, L.C.; Haase, V.H.; Johnson, R.S.; Schipani, E.; Clemens, T.L. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J. Clin. Invest., 2007, 117(6), 1616-1626.
[http://dx.doi.org/10.1172/JCI31581] [PMID: 17549257]
[37]
He, Y.X.; Zhang, G.; Pan, X.H.; Liu, Z.; Zheng, L.Z.; Chan, C.W.; Lee, K.M.; Cao, Y.P.; Li, G.; Wei, L.; Hung, L.K.; Leung, K.S.; Qin, L. Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model. Bone, 2011, 48(6), 1388-1400.
[http://dx.doi.org/10.1016/j.bone.2011.03.720] [PMID: 21421090]
[38]
Kim, B.S.; Yang, S.S.; You, H.K.; Shin, H.I.; Lee, J. Fucoidan-induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair. J. Tissue Eng. Regen. Med., 2018, 12(3), e1311-e1324.
[http://dx.doi.org/10.1002/term.2509] [PMID: 28714275]
[39]
Ding, H.; Chen, S.; Song, W.Q.; Gao, Y.S.; Guan, J.J.; Wang, Y.; Sun, Y.; Zhang, C.Q. Dimethyloxaloylglycine improves angiogenic activity of bone marrow stromal cells in the tissue-engineered bone. Int. J. Biol. Sci., 2014, 10(7), 746-756.
[http://dx.doi.org/10.7150/ijbs.8535] [PMID: 25013382]
[40]
Ollerenshaw, M.; Page, T.; Hammonds, J.; Demaine, A. Polymorphisms in the hypoxia inducible factor-1alpha gene (HIF1A) are associated with the renal cell carcinoma phenotype. Cancer Genet. Cytogenet., 2004, 153(2), 122-126.
[http://dx.doi.org/10.1016/j.cancergencyto.2004.01.014] [PMID: 15350301]
[41]
Shrestha, P.; Davis, D.A.; Veeranna, R.P.; Carey, R.F.; Viollet, C.; Yarchoan, R. Hypoxia-inducible factor-1 alpha as a therapeutic target for primary effusion lymphoma. PLoS Pathog., 2017, 13(9), e1006628.
[http://dx.doi.org/10.1371/journal.ppat.1006628] [PMID: 28922425]
[42]
Bruick, R.K.; McKnight, S.L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science, 2001, 294(5545), 1337-1340.
[http://dx.doi.org/10.1126/science.1066373] [PMID: 11598268]
[43]
Yuan, Q.; Bleiziffer, O.; Boos, A.M.; Sun, J.; Brandl, A.; Beier, J.P.; Arkudas, A.; Schmitz, M.; Kneser, U.; Horch, R.E. PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat. BMC Biotechnol., 2014, 14, 112.
[http://dx.doi.org/10.1186/s12896-014-0112-x] [PMID: 25543909]
[44]
Zhang, Y.; Yin, J.; Ding, H.; Zhang, C.; Gao, Y.S. Vitamin K2 ameliorates damage of blood vessels by glucocorticoid: A potential mechanism for its protective effects in glucocorticoid-induced osteonecrosis of the femoral head in a rat model. Int. J. Biol. Sci., 2016, 12(7), 776-785.
[http://dx.doi.org/10.7150/ijbs.15248] [PMID: 27313492]

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