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

• Published in: Scientific reports Vol. 7; no. 1; p. 44129
• Main Authors: Yu, Wei-Lin, Sun, Tuan-Wei, Qi, Chao, Zhao, Hua-Kun, Ding, Zhen-Yu, Zhang, Zhi-Wang, Sun, Ben-Ben, Shen, Ji, Chen, Feng, Zhu, Ying-Jie, Chen, Dao-Yun, He, Yao-Hua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-03-2017; Nature Publishing Group
• Subjects: 13/107; 13/51; 14/63; 631/61/54/152; 631/61/54/990; Angiogenesis; Biomaterials; Bone biomaterials; Bone growth; Bone marrow; Collagen; Controlled release; Fructose; Humanities and Social Sciences; Hydroxyapatite; Mesenchyme; Microspheres; multidisciplinary; Osteogenesis; Regeneration; Science; Simvastatin; Skin & tissue grafts; Stem cell transplantation; Stem cells; Vascularization
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep44129

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.