In Vivo Microcomputed Tomography of Nanocrystal-Doped Tissue Engineered Scaffolds.

In Vivo Microcomputed Tomography of Nanocrystal-Doped Tissue Engineered Scaffolds.
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DOI:
10.1021/acsbiomaterials.5b00476
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发表时间:
2016-04-11
影响因子:
5.8
通讯作者:
Shapiro EM
Shapiro EM
中科院分区:
工程技术2区
文献类型:
--
作者:
Forton SM;Latourette MT;Parys M;Kiupel M;Shahriari D;Sakamoto JS;Shapiro EM

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组织工程支架(TES)有望改善各种生物医学场景中基于细胞的治疗策略的结果,包括肌肉骨骼损伤,软组织修复和脊髓损伤。TES研究和开发以及临床使用的关键是植入后纵向监测TES位置、方向、完整性和微观结构的能力。在这里,我们描述了一种策略,使用微型计算机断层扫描(microCT)可视化TES植入小鼠后。TES掺杂有高度不透射线的氧化钆纳米晶体,并植入小鼠的后肢。小鼠在23周内接受连续microCT。TES在整个时间过程中清晰可见。藻酸盐支架在前6周内体积减少20%,在接下来的17周内稳定。琼脂糖支架体积不变。TES衰减在整个时间过程中也没有变化,表明没有溶解或泄漏。植入部位的组织学检查显示存在非常轻度的炎症,这是轻度异物反应的典型表现。血液检查显示肝酶显著升高,血液学测量白色血细胞计数显著降低。虽然将这些小鼠中X射线诱导的造血作用外推到人类并不简单,但显然这是一个需要仔细监测的领域。总之,这些数据提供了强有力的支持,即用不透射线的纳米晶体掺杂TES并进行microCT成像,代表了一种可能的策略,用于实现TES的连续体内监测。
Tissue engineered scaffolds (TES) hold promise for improving the outcome of cell-based therapeutic strategies for a variety of biomedical scenarios, including musculoskeletal injuries, soft tissue repair, and spinal cord injury. Key to TES research and development, and clinical use, is the ability to longitudinally monitor TES location, orientation, integrity, and microstructure following implantation. Here, we describe a strategy for using microcomputed tomography (microCT) to visualize TES following implantation into mice. TES were doped with highly radiopaque gadolinium oxide nanocrystals and were implanted into the hind limbs of mice. Mice underwent serial microCT over 23 weeks. TES were clearly visible over the entire time course. Alginate scaffolds underwent a 20% volume reduction over the first 6 weeks, stabilizing over the next 17 weeks. Agarose scaffold volumes were unchanged. TES attenuation was also unchanged over the entire time course, indicating a lack of nanocrystal dissolution or leakage. Histology at the implant site showed the presence of very mild inflammation, typical for a mild foreign body reaction. Blood work indicated marked elevation in liver enzymes, and hematology measured significant reduction in white blood cell counts. While extrapolation of the X-ray induced effects on hematopoiesis in these mice to humans is not straightforward, clearly this is an area for careful monitoring. Taken together, these data lend strong support that doping TES with radiopaque nanocrystals and performing microCT imaging, represents a possible strategy for enabling serial in vivo monitoring of TES.
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