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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.

SUBMITTER: Yu WL

PROVIDER: S-EPMC5347005 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration.

Yu Wei-Lin WL Sun Tuan-Wei TW Qi Chao C Zhao Hua-Kun HK Ding Zhen-Yu ZY Zhang Zhi-Wang ZW Sun Ben-Ben BB Shen Ji J Chen Feng F Zhu Ying-Jie YJ Chen Dao-Yun DY He Yao-Hua YH

Scientific reports 20170313

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 r ...[more]

PMID: 28287178

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Project description:BackgroundBone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown.MethodsMouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed.ResultsLLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2 or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β.ConclusionsLLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.

Dataset Information

Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration.

Publications

Enhanced osteogenesis and angiogenesis by mesoporous hydroxyapatite microspheres-derived simvastatin sustained release system for superior bone regeneration.

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