原位体内平台的骨膜组织工程,Biomaterials

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原位体内平台的骨膜组织工程
Biomaterials ( IF 12.8 ) Pub Date : 2017-01-14 14:29:09
J.G. Baldwin, F. Wagner, L.C. Martine, B.M. Holzapfel, C. Theodoropoulos, O. Bas, F.M. Savi, C. Werner, E.M. De-Juan-Pardo, D.W. Hutmacher

骨膜在骨稳态和再生中起关键作用。它包含为皮质骨提供重要血液供应的血管成分和作为骨形成细胞来源的成骨小生境。骨膜移植物在再生临界尺寸缺损方面已显示出希望，但是其有限的可用性限制了其广泛的临床应用。文献中仅报道了少量组织工程化的骨膜构建体（TEPC）。在开发合适的TEPC时当前面临的挑战是缺乏临床前模型，无法对其进行可靠的评估。在这项研究中，我们提出了一种新颖的骨膜组织工程概念，利用多相支架设计结合不同的人类细胞类型在原位体内平台中进行骨膜再生。人内皮和骨髓间充质干细胞（BM-MSC）分别用于反映血管和成骨的利基。免疫组织化学表明，BM-MSC保持其未分化表型。人内皮细胞发育成成熟的血管并连接到宿主脉管系统。与无细胞构建体相比，体外工程化的内皮网络的添加增加了血管形成。总之，结果表明，人类TEPC（hTEPC）成功地概括了天然骨膜的成骨和血管生态位，

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Periosteum tissue engineering in an orthotopic in vivo platform

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.

更新日期：2017-01-15

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