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Simultaneous three-dimensional visualization of mineralized and soft skeletal tissues by a novel microCT contrast agent with polyoxometalate structure
Biomaterials ( IF 14.0 ) Pub Date : 2017-12-22 , DOI: 10.1016/j.biomaterials.2017.12.016
Greet Kerckhofs , Steve Stegen , Nick van Gastel , Annelies Sap , Guillaume Falgayrac , Guillaume Penel , Marjorie Durand , Frank P. Luyten , Liesbet Geris , Katleen Vandamme , Tatjana Parac-Vogt , Geert Carmeliet

Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced microfocus computed tomography (CE-CT), a Hafnium-based Wells-Dawson polyoxometalate (Hf-POM), which allows simultaneous 3D visualization of mineralized and non-mineralized skeletal tissues, such as mineralized bone and bone marrow vasculature and adipocytes. We validated the novel contrast agent, which has a neutral pH in solution, by detailed comparison with (immuno)histology on murine long bones as blueprint, and showed that Hf-POM-based CE-CT can be used for virtual 3D histology. Furthermore, we quantified the 3D structure of the different skeletal tissues, as well as their spatial relation to each other, during aging and diet-induced obesity. We discovered, based on a single CE-CT dataset per sample, clear differences between the groups in bone structure, vascular network organization, characteristics of the adipose tissue and proximity of the different tissues to each other. These findings highlight the complementarity and added value of Hf-POM-based CE-CT compared to standard histomorphometry. As this novel technology provides a detailed 3D simultaneous representation of the structural organization of mineralized bone and bone marrow vasculature and adipose tissue, it will enable to improve insight in the interactions between these three tissues in several bone pathologies and to evaluate the in vivo performance of biomaterials for skeletal regeneration.



中文翻译:

新型具有多金属氧酸盐结构的microCT造影剂可同时对矿化和骨骼软组织进行三维三维可视化

生物组织具有复杂且异质的3D结构,通过2D的标准组织形态计量学只能部分显示出来。我们在此介绍一种用于对比增强型微聚焦计算机断层扫描(CE-CT)的新型化合物,该化合物是基于Ha的Wells-Dawson多金属氧酸盐(Hf-POM),它可以同时对矿化和未矿化的骨骼组织进行3D可视化,例如矿化的骨,骨髓血管和脂肪细胞。通过与鼠长骨上的(免疫)组织学进行比较,我们验证了溶液中具有中性pH值的新型造影剂,并将其作为蓝图,并表明基于Hf-POM的CE-CT可用于虚拟3D组织学。此外,我们在衰老和饮食诱发的肥胖症中量化了不同骨骼组织的3D结构以及它们彼此之间的空间关系。我们根据每个样品的一个CE-CT数据集发现,各组之间在骨结构,血管网络组织,脂肪组织的特征以及不同组织彼此之间的接近性之间存在明显差异。这些发现凸显了与标准组织形态测量法相比,基于Hf-POM的CE-CT的互补性和附加值。由于这项新技术提供了矿物质化的骨,骨髓血管和脂肪组织的结构组织的详细3D同步表示,因此它将能够改善对这三种组织在几种骨病理学中相互作用的了解,并评估 脂肪组织的特征以及不同组织彼此之间的接近性。这些发现凸显了与标准组织形态测量法相比,基于Hf-POM的CE-CT的互补性和附加值。由于这项新技术提供了矿物质化的骨,骨髓血管和脂肪组织的结构组织的详细3D同步表示,因此它将能够改善对这三种组织在几种骨病理学中相互作用的了解,并评估 脂肪组织的特征以及不同组织彼此之间的接近性。这些发现凸显了与标准组织形态测量法相比,基于Hf-POM的CE-CT的互补性和附加值。由于这项新技术提供了矿物质化的骨,骨髓血管和脂肪组织的结构组织的详细3D同步表示,因此它将能够改善对这三种组织在几种骨病理学中相互作用的了解,并评估生物材料在骨骼再生中的体内表现。

更新日期:2017-12-22
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