The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing
The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing
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DOI：
10.1007/s00264-013-2201-1
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发表时间：
2014-03-01
影响因子：
2.7
通讯作者：
Grgurevic, Lovorka
中科院分区：
文献类型：
--
作者：
Vukicevic, Slobodan;Oppermann, Hermann;Grgurevic, Lovorka
目的本研究的目的是修订商业BMP 2（Infuse）和BMP 7（Osigraft）为基础的骨装置的临床使用，并探讨低剂量的BMP 6在一种新型的全血生物相容性装置OSTEOGROW.Methods的作用和疗效的机制，从BMP 2和BMP 7的临床使用的并发症已系统地审查在骨重建的作用。已经通过μ CT和骨骼组织学在Bmp 6-/-小鼠中评估了BMP 6功能，并且还在间充质干细胞（MSC）、造血干细胞（HSC）和破骨细胞中进行了检查。OSTEOGROW的安全性和有效性进行了评估，在大鼠和rabbits.Results的BMP 2和BMP 7的临床使用问题已被归因于有限的理解，他们的作用在骨重建的时间设备开发的临床试验。骨器械中的BMP 2和BMP 7显著促进骨吸收，导致骨内膜表面的骨质溶解，同时刺激周围组织中的旺盛骨形成。骨器械中未结合的BMP 2和BMP 7沉淀在牛胶原蛋白上并引起炎症和肿胀。OSTEOGROW需要少量的BMP 6，应用于生物相容性血液凝固物载体中，用于刺激MSC的分化和加速动物中临界尺寸骨缺损的愈合，而没有骨吸收和炎症。BMP 6减少了破骨细胞的数量来自HSC，而BMP 2和BMP 7增加了他们的number.Conclusions目前的问题和挑战与商业骨设备可能会得到解决，通过使用新的BMP 6生物相容性设备OSTEOGROW，这将在干骺端骨折，BMP 2和BMP 7没有有效的车厢进行临床测试。
Purpose The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW.Methods Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/- mice by mu CT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits.Results Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of osteoclasts derived from HSC, while BMP2 and BMP7 increased their number.Conclusions Current issues and challenges with commercial bone devices may be resolved by using novel BMP6 biocompatible device OSTEOGROW, which will be clinically tested in metaphyseal bone fractures, compartments where BMP2 and BMP7 have not been effective.