Periosteum tissue engineering in an orthotopic in vivo platform
Periosteum tissue engineering in an orthotopic in vivo platform
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DOI：
10.1016/j.biomaterials.2016.11.016
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发表时间：
2017-03-01
期刊：
影响因子：
14
通讯作者：
Hutmacher, D. W.
中科院分区：
文献类型：
--
作者：
Baldwin, J. G.;Wagner, F.;Hutmacher, D. W.
骨膜在骨的动态平衡和再生中起着至关重要的作用。它包含一个为皮质骨提供重要血液供应的血管成分，以及一个作为骨形成细胞来源的成骨利基。骨膜移植在修复临界大小的骨缺损方面显示出良好的前景，但其有限的可用性限制了其在临床上的广泛应用。仅有少量的组织工程骨膜结构(TEPC)在文献中被报道。目前开发合适的TEPC的一个挑战是缺乏能够可靠评估它们的临床前模型。在这项研究中，我们提出了一种新的骨膜组织工程概念，利用多相支架设计并结合不同类型的人细胞在体内原位平台上进行骨膜再生。人内皮细胞和骨髓间充质干细胞(BM-MSCs)分别用于反映血管和成骨的生态位。免疫组织化学显示BM-MSCs维持其未分化表型。人的内皮细胞发育成成熟的血管，并与宿主血管系统相连。与无细胞构建相比，体外工程化内皮细胞网络的加入增加了血管的形成。结果表明，人TEPC(HTEPC)成功地再现了天然骨膜的成骨和血管生态位，所提出的原位异种移植模型为评估基于支架的组织工程概念利用人类细胞提供了合适的体内环境。皇冠版权所有(C)2016由爱思唯尔有限公司出版。保留所有权利。
The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated.In this study, we present a novel periosteum tissue engineering concept utilizing a multiphasic scaffold design in combination with different human cell types for periosteal regeneration in an orthotopic in vivo platform. Human endothelial and bone marrow mesenchymal stem cells (BM-MSCs) were used to mirror both the vascular and osteogenic niche respectively. Immunohistochemistry showed that the BM-MSCs maintained their undifferentiated phenotype. The human endothelial cells developed into mature vessels and connected to host vasculature. The addition of an in vitro engineered endothelial network increased vascularization in comparison to cell-free constructs.Altogether, the results showed that the human TEPC (hTEPC) successfully recapitulated the osteogenic and vascular niche of native periosteum, and that the presented orthotopic xenograft model provides a suitable in vivo environment for evaluating scaffold-based tissue engineering concepts exploiting human cells. Crown Copyright (C) 2016 Published by Elsevier Ltd. All rights reserved.