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宏观和微观流动在骨骼再生医学中的应用。

Macro and microfluidic flows for skeletal regenerative medicine.

机构信息

Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln 68588, NE, USA.

出版信息

Cells. 2012 Dec 11;1(4):1225-45. doi: 10.3390/cells1041225.

DOI:10.3390/cells1041225
PMID:24710552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3901127/
Abstract

Fluid flow has a great potential as a cell stimulatory tool for skeletal regenerative medicine, because fluid flow-induced bone cell mechanotransduction in vivo plays a critical role in maintaining healthy bone homeostasis. Applications of fluid flow for skeletal regenerative medicine are reviewed at macro and microscale. Macroflow in two dimensions (2D), in which flow velocity varies along the normal direction to the flow, has explored molecular mechanisms of bone forming cell mechanotransduction responsible for flow-regulated differentiation, mineralized matrix deposition, and stem cell osteogenesis. Though 2D flow set-ups are useful for mechanistic studies due to easiness in in situ and post-flow assays, engineering skeletal tissue constructs should involve three dimensional (3D) flows, e.g., flow through porous scaffolds. Skeletal tissue engineering using 3D flows has produced promising outcomes, but 3D flow conditions (e.g., shear stress vs. chemotransport) and scaffold characteristics should further be tailored. Ideally, data gained from 2D flows may be utilized to engineer improved 3D bone tissue constructs. Recent microfluidics approaches suggest a strong potential to mimic in vivo microscale interstitial flows in bone. Though there have been few microfluidics studies on bone cells, it was demonstrated that microfluidic platform can be used to conduct high throughput screening of bone cell mechanotransduction behavior under biomimicking flow conditions.

摘要

流体流动作为一种骨骼再生医学的细胞刺激工具具有很大的潜力,因为在体内,流体流动诱导的骨细胞力学转导对于维持健康的骨稳态起着关键作用。本文综述了在宏观和微观尺度上应用流体流动进行骨骼再生医学的研究。二维(2D)宏观流动中,流速沿垂直于流动方向变化,探索了负责调节分化、矿化基质沉积和干细胞成骨的成骨细胞力学转导的分子机制。尽管 2D 流动设置由于原位和流动后检测的便利性而非常适合于力学研究,但工程化骨骼组织构建物应涉及三维(3D)流动,例如,通过多孔支架的流动。使用 3D 流动的骨骼组织工程已经产生了有希望的结果,但 3D 流动条件(例如剪切应力与化学输送)和支架特性应进一步定制。理想情况下,可以利用从 2D 流动中获得的数据来设计改进的 3D 骨组织构建物。最近的微流控方法表明,在骨骼中模拟体内微尺度间质流动具有很大的潜力。尽管关于骨细胞的微流控研究很少,但已经证明微流控平台可用于在仿生流动条件下进行骨细胞力学转导行为的高通量筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/282d39e3a8a8/cells-01-01225-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/7bf98fb70d68/cells-01-01225-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/e1e03777f9e5/cells-01-01225-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/8a521aadaad0/cells-01-01225-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/282d39e3a8a8/cells-01-01225-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/7bf98fb70d68/cells-01-01225-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/e1e03777f9e5/cells-01-01225-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/8a521aadaad0/cells-01-01225-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8924/3901127/282d39e3a8a8/cells-01-01225-g004.jpg

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Integr Biol (Camb). 2012 Sep;4(9):1008-18. doi: 10.1039/c2ib20080e.
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Perfusion flow enhances osteogenic gene expression and the infiltration of osteoblasts and endothelial cells into three-dimensional calcium phosphate scaffolds.灌注流可增强成骨基因表达,并促进成骨细胞和内皮细胞向三维磷酸钙支架内浸润。
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用于共培养间充质干细胞以实现血管化骨组织工程的微工程平台。
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