Elastin-like-polypeptide based fusion proteins for osteogenic factor delivery in bone healing
Elastin-like-polypeptide based fusion proteins for osteogenic factor delivery in bone healing
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DOI：
10.1002/btpr.2269
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发表时间：
2016-07-01
影响因子：
2.9
通讯作者：
Koria, Piyush
中科院分区：
文献类型：
--
作者：
McCarthy, Bryce;Yuan, Yuan;Koria, Piyush
骨损伤和骨疾病的现代治疗越来越依赖于使用生长因子来刺激骨生长。骨形态发生蛋白-2 （BMP-2）是一种有效的成骨诱导蛋白，在治疗模型中显示出有希望的结果，但最近由于缺乏局部保留，异位骨形成和潜在的致死性炎症，其实际疗效受到质疑。在需要新的BMP-2递送技术的地方，我们证明了含有BMP-2的弹性蛋白样肽（ELP）融合蛋白递送BMP-2的可行性。该融合蛋白保留了BMP-2和ELP的性能特征。融合蛋白被发现可以诱导间充质干细胞的成骨分化，在融合蛋白的作用下产生碱性磷酸酶和细胞外钙沉积。保留ELPs的反相转变特性使得融合蛋白可以在细菌宿主（如大肠杆菌）中表达，并且可以使用反相转变循环轻松快速地纯化。融合蛋白在人体温度下形成自聚集的纳米颗粒。收集的数据表明，这些融合蛋白纳米颗粒作为骨治疗中BMP-2的剂量效率和位置精确的无细胞毒性递送载体的可行性。(c) 2016年美国化学工程师协会生物技术。掠夺。， 32:1029-1037, 2016
Modern treatments of bone injuries and diseases are becoming increasingly dependent on the usage of growth factors to stimulate bone growth. Bone morphogenetic protein-2 (BMP-2), a potent osteogenic inductive protein, exhibits promising results in treatment models, but recently has had its practical efficacy questioned due to the lack of local retention, ectopic bone formation, and potentially lethal inflammation. Where a new delivery technique of the BMP-2 is necessary, here we demonstrate the viability of an elastin-like peptide (ELP) fusion protein containing BMP-2 for delivery of the BMP-2. This fusion protein retains the performance characteristics of both the BMP-2 and ELP. The fusion protein was found to induce osteogenic differentiation of mesenchymal stem cells as evidenced by the production of alkaline phosphatase and extracellular calcium deposits in response to treatment by the fusion protein. Retention of the ELPs inverse phase transition property has allowed for expression of the fusion protein within a bacterial host (such as Escherichia coli) and easy and rapid purification using inverse transition cycling. The fusion protein formed self-aggregating nanoparticles at human-body temperature. The data collected suggests the viability of these fusion protein nanoparticles as a dosage-efficient and location-precise noncytotoxic delivery vehicle for BMP-2 in bone treatment. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1029-1037, 2016