首页> 外文期刊>British Biotechnology Journal >Enhancement of Bone Formation by BoneMorphogenetic Protein-2 Released from Poly(L-lactic-co-glycolic acid) Microsphere
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Enhancement of Bone Formation by BoneMorphogenetic Protein-2 Released from Poly(L-lactic-co-glycolic acid) Microsphere

机译:聚(L-乳酸-乙醇酸)微球释放的骨形成蛋白2增强骨形成。

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An appropriate carrier acting as a sustained delivery vehicle for bone morphogenetic proteins (BMPs) is required for the maximal clinical effectiveness of these osteogenic proteins to enhance bone formation. The purpose of this study was to evaluate a low-molecular-weight poly(L-lactic-co-glycolic acid) (PLGA) copolymer as a synthetic, biodegradable carrier for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then to address the hypothesis that BMP-2 delivery from this vehicle could promote cell proliferation in vitro and ectopic bone formation in vivo. The BMP-2 was entrapped in microspheres of PLGA by using an improved water-in-oil-in water double-emulsion-solvent-extraction technique. The in vitro release kinetics of rhBMP-2 was determined by ELISA. Then we verified the effect of the sustained delivery vehicle on MSC cell proliferation. The ectopic bone induction in intramuscular implants of mice was evaluated at 2 and 4 weeks post-implantation. The results showed the PLGA microsphere released a total of 14.2%±0.71% rhBMP-2 at the initial phase followed by a prolonged release for 28 days. The rhBMP-2 released from the PLGA microsphere stimulated an increase in alkaline phosphatase (ALP) activity of MSC cells for 5 days in vitro, suggesting that the delivery vehicle releases BMP-2 for a prolonged period in an active form. Moreover, the released rhBMP-2 from the PLGA microsphere significantly promoted MSC cells proliferation after days 5 in culture. In vivo bone formation studies showed the rhBMP-2-loaded PLGA microsphere induced ectopic bone formation to a much greater extent than did rhBMP-2 treated mice. These results demonstrated that the PLGA copolymer material is capable of potentiating the osteogenic efficacy of BMP-2 and, as such, represents a promising delivery vehicle for BMP-2 for orthopedic and dental repair.
机译:这些成骨蛋白增强骨形成的最大临床有效性需要合适的载体作为骨形态发生蛋白(BMP)的持续递送载体。这项研究的目的是评估低分子量聚(L-乳酸-乙醇酸)(PLGA)共聚物作为合成,可生物降解的载体,以持续递送骨形态发生蛋白2(BMP-2) ,然后解决这一假说,即从该载体中递送BMP-2可以促进体外细胞增殖和体内异位骨形成。通过使用改进的水包油包水型双乳液溶剂萃取技术,将BMP-2包埋在PLGA微球中。通过ELISA确定rhBMP-2的体外释放动力学。然后,我们验证了持续递送载体对MSC细胞增殖的影响。在植入后2和4周评估小鼠肌肉内植入物中的异位骨诱导。结果表明,PLGA微球在初始阶段总共释放了14.2%±0.71%的rhBMP-2,随后延长释放28天。从PLGA微球释放的rhBMP-2在体外刺激MSC细胞的碱性磷酸酶(ALP)活性增加了5天,这表明递送载体以活性形式长时间释放了BMP-2。此外,从PLGA微球释放的rhBMP-2在培养第5天后显着促进了MSC细胞的增殖。体内骨形成研究表明,与rhBMP-2处理的小鼠相比,负载rhBMP-2的PLGA微球诱导的异位骨形成的程度要大得多。这些结果证明,PLGA共聚物材料能够增强BMP-2的成骨功效,因此,代表了用于骨科和牙齿修复的BMP-2的有希望的递送载体。

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