The role of simvastatin in the osteogenesis of injectable tissue-engineered bone based on human adipose-derived stromal cells and platelet-rich plasma

Zhou, Yongsheng; Ni, Yongwei; Liu, Yunsong; Zeng, Bai Jin; Xu, Yan; Ge, Wenshu

doi:10.1016/j.biomaterials.2010.03.037

Cited by 74 publications

(74 citation statements)

References 33 publications

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“…This unique characteristic was found in other statin-induced cells such as BMSCs or MC3T3-E1. 15,[41][42][43][44] In our study, SIM significantly stimulated osteogenic gene expression of RUNX-2, BMP-2, ALP, and OC ( Figure 6) and final mineralization (Figures 6 and 7) in the SIM/COL/PET groups. This result indicates that the SIM/collagen coating can modify the surface of the PET artificial ligament grafts.…”

Section: Discussionsupporting

confidence: 61%

“…Previous studies have shown that SIM reduces osteoclast and increases osteoblast activity and accelerates bone formation locally. 39,40 Zhou et al 41 reported that SIM significantly increased BMP-2, Cbfa1, VEGF, and fibroblast growth factor-2 mRNA expression. Furthermore, SIM can enhance the expression of BMP-2.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the release of SIM by the coating may be advantageous for providing an initial stimulation of the local cells to express BMP-2, which can directly induce osteoblastic differentiation by driving the expression of Cbfa1. 41 The delivery system for SIM is very important because the effectiveness of SIM depends on the rhythm in which the carrier releases the drug, as well as on its local concentration. High systemic (oral) administration of SIM may increase the risk for liver damage and kidney disease.…”

Section: Discussionmentioning

confidence: 99%

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Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Zhang

Han

et al. 2016

IJN

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The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL) reconstruction. But the biological graft–bone healing still remains a problem. Previous studies have shown that simvastatin (SIM) stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low-dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET) artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen-coated PET scaffolds (COL/PET) and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET) proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells’ osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft–bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM-sustained release from SIM/COL/PET promoted the graft–bone healing via its effect on both angiogenesis and osteogenesis. This study suggested that collagen containing low-dose SIM microsphere coating on the surface of PET artificial ligaments could be potentially applied for ACL reconstruction.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Zhang

Han

et al. 2016

IJN

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“…9 Several small molecules, such as statins and immunosuppressants (e.g., FK506, cyclosporine A), have been shown to induce osteogenic differentiation in vitro and bone formation in vivo. [10][11][12][13] In particular, phenamil is a derivative of the FDA-approved diuretic amiloride, and it has been found to be a strong activator of BMP signaling.…”

Section: Introductionmentioning

confidence: 99%

Delivery of Phenamil Enhances BMP-2-Induced Osteogenic Differentiation of Adipose-Derived Stem Cells and Bone Formation in Calvarial Defects

Fan

Cui

et al. 2015

Tissue Engineering Part A

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Bone morphogenetic proteins (BMPs) have been widely used for bone repair in the craniofacial region. However, its high dose requirement in clinical applications revealed adverse effects and inefficient bone formation, along with high cost. Here, we report a novel osteoinductive strategy to effectively complement the osteogenic activity of BMP-2 using phenamil, a small molecule that can induce osteogenic differentiation via stimulation of BMP signaling. Treatment of adipose-derived stem cells (ASCs) with BMP-2 in combination with phenamil significantly promoted the in vitro osteogenic differentiation of ASCs. The efficacy of the combination strategy of phenamil + BMP-2 was further confirmed in a mouse calvarial defect model using scaffolds consisting of poly(lactic-co-glycolic acid) and apatite layer on their surfaces designed to slowly release phenamil and BMP-2. Six weeks after implantation, the scaffolds treated with phenamil + BMP-2 significantly promoted mouse calvarial regeneration as demonstrated by micro-computerized tomography and histology, compared with the groups treated with phenamil or BMP-2 alone. Moreover, the combination treatment reduced the BMP-2 dose without compromising calvarial healing efficacy. These results suggest promising complementary therapeutic strategies for bone repair in more efficient and cost-effective manners.

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“…Any interruption in bone remodeling, such as menopause, will disturb the balance between formation and resorption and cause bone mass loss [16]. Therefore, we used OVX rats as an animal model for human osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Anti-osteoporosis effect of <i>Cistanche deserticola</i> Ma extract in ovariectomized rats

Zhang¹,

Yue²,

Zhang³

et al. 2016

Trop. J. Pharm Res

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The role of simvastatin in the osteogenesis of injectable tissue-engineered bone based on human adipose-derived stromal cells and platelet-rich plasma

Cited by 74 publications

References 33 publications

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

Delivery of Phenamil Enhances BMP-2-Induced Osteogenic Differentiation of Adipose-Derived Stem Cells and Bone Formation in Calvarial Defects

Anti-osteoporosis effect of <i>Cistanche deserticola</i> Ma extract in ovariectomized rats

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