Combination of Î²-TCP and BMP-2 gene-modified bMSCs to heal critical size mandibular defects in rats

Zhao, Jun; Hu, Jingzhou; Wang, S; Sun, Xiaojuan; Xia, Lunguo; Zhang, X; Zhang, Z; Jiang, Xinquan

doi:10.1111/j.1601-0825.2009.01602.x

Cited by 48 publications

(41 citation statements)

References 39 publications

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“…Calcium-phosphatecontaining biomaterials that possess osteoconductive properties are promising scaffolds for tissue engineering, particularly in bone regeneration. β-TCP posesses a porous structure and prominent bioresorbable properties (Zhao et al 2010). We successfully repaired class III furcation defects in Beagle dogs by using β-TCP as a scaffold .…”

Section: Discussionmentioning

confidence: 94%

Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin

et al. 2015

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Osteoporosis leads to increased bone fractures and net bone loss, in part because of the dysfunction of bone marrow stromal cells (BMSCs). Leptin is an adipokine that plays important roles in many biological processes, including the regulation of the actions of mesenchymal stem cells. Our aim is to investigate the osteogenic effects of leptin in osteoporotic BMSCs in vitro and in vivo. The leptin gene was transferred into BMSCs isolated from osteoporotic rats by using recombinant adenoviruses. Once the gene and protein expression of leptin had been confirmed, MTT assays were performed; leptin overexpression was confirmed not to affect the viability of osteoporotic BMSCs. However, alkaline phosphatase (ALP) activity measurements, Alizarin red staining and analyses by quantitative real-time reverse transcription with the polymerase chain reaction revealed that leptin upregulated ALP activity, mineral deposition and the mRNA levels of runt-related transcription factor 2, ALP and collagen type І. Lastly, the effects of leptin on osteogenic differentiation were assessed in vivo. Cells transfected with leptin exhibited increased osteogenic differentiation and enhanced formation of bone-like structures. This study thus reveals, for the first time, that the overexpression of leptin in osteoporotic BMSCs (1) enhances their capacity to differentiate into osteoblasts and to form bone-like tissue and (2) might be a useful skeletal regenerative therapy in osteoporotic patients.

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Section: Discussionmentioning

confidence: 94%

Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin

et al. 2015

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“…BMP-2 plays a central role in many steps during bone regeneration. During bone healing, BMP-2 stimulates both osteoblast proliferation and differentiation [32], recruits undifferentiated mesenchymal cells from peripheral tissues and facilitates precursor cell differentiation into bone-forming cells [28, 33]. BMP-2 has demonstrated powerful in vivo osteogenic ability when applied locally and has been recognized as one of the most potent osteoinductive growth factors [34-37].…”

Section: Introductionmentioning

confidence: 99%

The use of injectable sonication-induced silk hydrogel for VEGF165 and BMP-2 delivery for elevation of the maxillary sinus floor

et al. 2011

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Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF165) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared in vitro and the slow release of VEGF165 and BMP-2 from these silk gels was evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF165 (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF165/BMP-2 (group V+B) (n=6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF165 promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V+B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V+B were larger than those of the Silk gel and VEGF groups, and the V+B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V+B. In conclusion, VEGF165 and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities.

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“…BMSCs were isolated and cultured following established protocols, as previously described. 29 BMSCs were passaged twice before use.…”

Section: Cell Culturementioning

confidence: 99%

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Zhang¹,

Yu²,

Wang³

et al. 2018

IJN

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Introduction To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2) are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods A new growth factor delivery system was fabricated using BMP-2-loaded TiO 2 nanotubes by lyophilization with trehalose (TiO 2 -Lyo-Tre-BMP-2). We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT), sequential fluorescent labelling, and histological analysis. Results Compared with absorbed BMP-2-loaded TiO 2 nanotubes (TiO 2 -BMP-2), TiO 2 -Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO 2 -Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO 2 -BMP-2 nanotubes. Conclusion Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects.

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Combination of Î²-TCP and BMP-2 gene-modified bMSCs to heal critical size mandibular defects in rats

Cited by 48 publications

References 39 publications

Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin

Increased osteogenesis in osteoporotic bone marrow stromal cells by overexpression of leptin

The use of injectable sonication-induced silk hydrogel for VEGF165 and BMP-2 delivery for elevation of the maxillary sinus floor

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

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