Engineering axially vascularized bone in the sheep arteriovenous-loop model
Engineering axially vascularized bone in the sheep arteriovenous-loop model
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DOI：
10.1002/term.1457
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发表时间：
2013-08-01
影响因子：
3.3
通讯作者：
Beier, Justus P.
中科院分区：
文献类型：
--
作者：
Boos, Anja M.;Loew, Johanna S.;Beier, Justus P.
血管供应不足的复杂骨缺损的治疗仍然是一个挑战。为了克服自体移植物的局限性，最近建立了绵羊模型，其特征在于生物人工结构的独立轴向血管化的发展，允许显微外科移植。为了在绵羊动静脉袢模型中构建独立的轴向血管化骨组织，在本研究中，将间充质干细胞（MSCs）与重组人骨形态发生蛋白-2（rhBMP-2）联合或不联合，并与磷酸三钙-羟基磷灰石（-TCP-HA）颗粒联合直接自体移植到绵羊体内。术后12周，组织学和免疫组织化学评价显示两组均有新骨形成。用rhBMP-2刺激直接自体移植的MSC获得了增加的骨面积。成骨细胞和成骨细胞检测到邻近新形成的骨，揭示了一个积极的骨重建过程。直接自体移植的MSC可以被发现接近-TCP-HA颗粒，并有助于骨形成。随着时间的推移，磁共振成像（MRI）和微型计算机断层扫描（CT）成像证实了AV环引起的致密血管化。本研究显示，在绵羊AV-环模型中，使用直接自体移植的MSC和rhBMP-2刺激，在约12周内，以临床显著量重新工程化独立轴向血管化的可移植骨组织。这种工程化血管化可移植骨组织的策略将来可能会转移到临床，以增强当前的重建策略。版权所有（c）2012约翰威利父子有限公司
Treatment of complex bone defects in which vascular supply is insufficient is still a challenge. To overcome the limitations from autologous grafts, a sheep model has been established recently, which is characterized by the development of an independent axial vascularization of a bioartificial construct, permitting microsurgical transplantation. To engineer independently axially vascularized bone tissue in the sheep arteriovenous (AV)-loop model, mesenchymal stem cells (MSCs), without and in combination with recombinant human bone morphogenetic protein-2 (rhBMP-2), were harvested and directly autotransplanted in combination with -tricalcium phosphate-hydroxyapatite (-TCP-HA) granules into sheep in this study. After explantation after 12weeks, histological and immunohistochemical evaluation revealed newly formed bone in both groups. An increased amount of bone area was obtained using directly autotransplanted MSCs with rhBMP-2 stimulation. Osteoblastic and osteoclastic cells were detected adjacent to the newly formed bone, revealing an active bone remodelling process. Directly autotransplanted MSCs can be found close to the -TCP-HA granules and are contributing to bone formation. Over time, magnetic resonance imaging (MRI) and micro-computed tomography (CT) imaging confirmed the dense vascularization arising from the AV-loop. This study shows de novo engineering of independently axially vascularized transplantable bone tissue in clinically significant amounts, using directly autotransplanted MSCs and rhBMP-2 stimulation in about 12weeks in the sheep AV-loop model. This strategy of engineering vascularized transplantable bone tissue could be possibly transferred to the clinic in the future in order to augment current reconstructive strategies. Copyright (c) 2012 John Wiley & Sons, Ltd.