Spatially controlled rhBMP-2 mediated calvarial bone formation in a transgenic mouse model

Spatially controlled rhBMP-2 mediated calvarial bone formation in a transgenic mouse model
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DOI:
10.1016/j.ijbiomac.2017.08.116
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发表时间:
2018-01-01
影响因子:
8.2
通讯作者:
Nair, Lakshmi S.
Nair, Lakshmi S.
中科院分区:
化学1区
文献类型:
--
作者:
Gohil, Shalini V.;Wang, Liping;Nair, Lakshmi S.

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本研究旨在研究重组人骨形成蛋白-2(rhBMP-2)在可酶交联型乙二醇壳聚糖水凝胶中的局部成骨活性。采用临界大小的双侧颅骨缺损区模型,其中一个缺损区植入rhBMP-2水凝胶(HPP-GC+BMP)。邻近的缺损处植入了一种骨传导、胶原羟基磷灰石基质“Healos(R)”。植入HPP-GC+BMP后4周,临界大小的缺损区完全闭合。然而,植入Healos(R)的邻近部位没有显示任何骨形成。从Co13.6转基因动物分离的颅骨进行组织学和组织形态计量学分析,证实了在成骨细胞和成骨前细胞中表达荧光的hBMP-2生物活性在细胞水平上的空间调控。在HPPGC+BMP种植体中保留的rhBMP-2能够在种植部位定位成骨细胞的聚集和成骨。结果表明,与胶原羟基磷灰石支架相比,HPP-GC水凝胶可以最大限度地减少rhBMP-2从种植部位的扩散损失。(C)2017爱思唯尔B.V.保留所有权利。
The study aimed to investigate the localized osteogenic activity of recombinant human bone morphogenetic protein (rhBMP-2), when delivered using enzymatically crosslinkable injectable glycol chitosan hydrogel. A critical sized bilateral calvarial defect model was used wherein one defect was implanted with rhBMP-2 loaded hydrogel (HPP-GC + BMP). The neighboring defect was implanted with an osteoconductive, collagen hydroxyapatite matrix "Healos (R)". The implantation of HPP-GC + BMP led to complete closure of the critical sized defect at 4 weeks post-implantation. The neighboring site implanted with Healos (R) however, did not show any bone formation. The spatial control of rhBMP-2 bioactivity at the cellular level was confirmed by histological and histomorphometric analysis of the calvaria isolated from Co13.6 transgenic animals which can express fluorescence in osteoblast and pre-osteoblast cells. The retained rhBMP-2 in HPPGC+ BMP implant was able to localize osteoprogenitor recruitment and osteogenesis, at the implantation site. The results demonstrate the efficacy of HPP-GC hydrogel in minimizing the diffusive loss of rhBMP-2 from the implantation site, compared to the collagen hydroxyapatite scaffold. (C) 2017 Elsevier B.V. All rights reserved.