Enhanced Osteogenesis and Angiogenesis by Mesoporous Hydroxyapatite Microspheres-derived Simvastatin Sustained Release System for Superior Bone Regeneration

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 14

PMID 28287178

Citations 29

Authors

Wei-Lin Yu

Tuan-Wei Sun

Chao Qi

Hua-Kun Zhao

Zhen-Yu Ding

Zhi-Wang Zhang

Ben-Ben Sun

Ji Shen

Feng Chen

Ying-Jie Zhu

Dao-Yun Chen

Yao-Hua He

Affiliations

Soon will be listed here.

Abstract

Biomaterials with both excellent osteogenic and angiogenic activities are desirable to repair massive bone defects. In this study, simvastatin with both osteogenic and angiogenic activities was incorporated into the mesoporous hydroxyapatite microspheres (MHMs) synthesized through a microwave-assisted hydrothermal method using fructose 1,6-bisphosphate trisodium salt (FBP) as an organic phosphorous source. The effects of the simvastatin-loaded MHMs (S-MHMs) on the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and angiogenesis in EA.hy926 cells were investigated. The results showed that the S-MHMs not only enhanced the expression of osteogenic markers in rBMSCs but also promoted the migration and tube formation of EA.hy926 cells. Furthermore, the S-MHMs were incorporated into collagen matrix to construct a novel S-MHMs/collagen composite scaffold. With the aid of MHMs, the water-insoluble simvastatin was homogenously incorporated into the hydrophilic collagen matrix and presented a sustained release profile. In vivo experiments showed that the S-MHMs/collagen scaffolds enhanced the bone regeneration and neovascularization simultaneously. These results demonstrated that the water-insoluble simvastatin could be incorporated into the MHMs and maintained its biological activities, more importantly, the S-MHMs/collagen scaffolds fabricated in this study are of immense potential in bone defect repair by enhancing osteogenesis and angiogenesis simultaneously.

Citing Articles

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References

Shi M, Zhou Y, Shao J, Chen Z, Song B, Chang J . Stimulation of osteogenesis and angiogenesis of hBMSCs by delivering Si ions and functional drug from mesoporous silica nanospheres. Acta Biomater. 2015; 21:178-89. DOI: 10.1016/j.actbio.2015.04.019. View

Fukui T, Ii M, Shoji T, Matsumoto T, Mifune Y, Kawakami Y . Therapeutic effect of local administration of low-dose simvastatin-conjugated gelatin hydrogel for fracture healing. J Bone Miner Res. 2012; 27(5):1118-31. DOI: 10.1002/jbmr.1558. View

Lamalice L, Le Boeuf F, Huot J . Endothelial cell migration during angiogenesis. Circ Res. 2007; 100(6):782-94. DOI: 10.1161/01.RES.0000259593.07661.1e. View

Asai J, Takenaka H, Hirakawa S, Sakabe J, Hagura A, Kishimoto S . Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis. Am J Pathol. 2012; 181(6):2217-24. DOI: 10.1016/j.ajpath.2012.08.023. View

Dickson K, Katzman S, Paiement G . The importance of the blood supply in the healing of tibial fractures. Contemp Orthop. 1995; 30(6):489-93. View

Yu M, Zhou K, Li Z, Zhang D . Preparation, characterization and in vitro gentamicin release of porous HA microspheres. Mater Sci Eng C Mater Biol Appl. 2014; 45:306-12. DOI: 10.1016/j.msec.2014.08.075. View

Quinlan E, Partap S, Azevedo M, Jell G, Stevens M, OBrien F . Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair. Biomaterials. 2015; 52:358-66. DOI: 10.1016/j.biomaterials.2015.02.006. View

Naito Y, Terukina T, Galli S, Kozai Y, Vandeweghe S, Tagami T . The effect of simvastatin-loaded polymeric microspheres in a critical size bone defect in the rabbit calvaria. Int J Pharm. 2013; 461(1-2):157-62. DOI: 10.1016/j.ijpharm.2013.11.046. View

Carletti E, Motta A, Migliaresi C . Scaffolds for tissue engineering and 3D cell culture. Methods Mol Biol. 2010; 695:17-39. DOI: 10.1007/978-1-60761-984-0_2. View

10.

Zheng L, Jiang X, Chen X, Fan H, Zhang X . Evaluation of novel in situ synthesized nano-hydroxyapatite/collagen/alginate hydrogels for osteochondral tissue engineering. Biomed Mater. 2014; 9(6):065004. DOI: 10.1088/1748-6041/9/6/065004. View

11.

Choi K, Lee M, Kwon T, Nah H, Furuichi T, Komori T . Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development. Dev Dyn. 2005; 233(1):115-21. DOI: 10.1002/dvdy.20323. View

12.

Maeda T, Matsunuma A, Kurahashi I, Yanagawa T, Yoshida H, Horiuchi N . Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem. 2004; 92(3):458-71. DOI: 10.1002/jcb.20074. View

13.

Baek K, Lee W, Oh K, Tae H, Lee J, Lee E . The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells. J Korean Med Sci. 2005; 20(3):438-44. PMC: 2782200. DOI: 10.3346/jkms.2005.20.3.438. View

14.

Chen D, Zhang X, He Y, Lu J, Shen H, Jiang Y . Co-culturing mesenchymal stem cells from bone marrow and periosteum enhances osteogenesis and neovascularization of tissue-engineered bone. J Tissue Eng Regen Med. 2011; 6(10):822-32. DOI: 10.1002/term.489. View

15.

Bouletreau P, Warren S, Spector J, Peled Z, Gerrets R, Greenwald J . Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing. Plast Reconstr Surg. 2002; 109(7):2384-97. DOI: 10.1097/00006534-200206000-00033. View

16.

Bae M, Yang D, Lee J, Heo D, Kwon Y, Youn I . Photo-cured hyaluronic acid-based hydrogels containing simvastatin as a bone tissue regeneration scaffold. Biomaterials. 2011; 32(32):8161-71. DOI: 10.1016/j.biomaterials.2011.07.045. View

17.

Yueyi C, Xiaoguang H, Jingying W, Quansheng S, Jie T, Xin F . Calvarial defect healing by recruitment of autogenous osteogenic stem cells using locally applied simvastatin. Biomaterials. 2013; 34(37):9373-80. DOI: 10.1016/j.biomaterials.2013.08.060. View

18.

Thirunavukkarasu M, Selvaraju V, Rao Dunna N, Foye J, Joshi M, Otani H . Simvastatin treatment inhibits hypoxia inducible factor 1-alpha-(HIF-1alpha)-prolyl-4-hydroxylase 3 (PHD-3) and increases angiogenesis after myocardial infarction in streptozotocin-induced diabetic rat. Int J Cardiol. 2013; 168(3):2474-80. DOI: 10.1016/j.ijcard.2013.03.005. View

19.

Moshiri A, Shahrezaee M, Shekarchi B, Oryan A, Azma K . Three-Dimensional Porous Gelapin-Simvastatin Scaffolds Promoted Bone Defect Healing in Rabbits. Calcif Tissue Int. 2015; 96(6):552-64. DOI: 10.1007/s00223-015-9981-9. View

20.

Ehrlich M, Gutman O, Knaus P, Henis Y . Oligomeric interactions of TGF-β and BMP receptors. FEBS Lett. 2012; 586(14):1885-96. DOI: 10.1016/j.febslet.2012.01.040. View