title: Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration.
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.
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Yu
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China.|University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
authors.forename: Tuan-Wei
authors.initials: TW
authors.lastname: Sun
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China.|University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Hua-Kun
authors.initials: HK
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Ding
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Zhi-Wang
authors.initials: ZW
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Ben-Ben
authors.initials: BB
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Shen
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China.|University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China.|University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing 100049, China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Dao-Yun
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.|Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, 600 Yishan Road, Shanghai 200233, China.
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: He
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D017886:Durapatite; D019821:Simvastatin