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机械刺激在软骨组织工程生物反应器中的应用进展

Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

作者信息

Li Ke, Zhang Chunqiu, Qiu Lulu, Gao Lilan, Zhang Xizheng

机构信息

Tianjin Key Laboratory of Design and Intelligent Control of the Advanced Mechatronical System, School of Mechanical Engineering, Tianjin University of Technology , Tianjin, China .

出版信息

Tissue Eng Part B Rev. 2017 Aug;23(4):399-411. doi: 10.1089/ten.TEB.2016.0427. Epub 2017 May 24.

Abstract

Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers often ignore the importance of biochemical factors to the growth and development of engineered cartilage. In our point of view, only by fully considering synergistic effects of mechanical and biochemical factors can we find appropriate culture conditions for functional cartilage constructs. Once again, rolling-sliding-compression load under appropriate biochemical conditions may be conductive to realize the adaptive development between the structure and function of engineered cartilage in vitro.

摘要

关节软骨(AC)是滑膜关节中的承重组织。由于其无血管性,一旦受到损伤或疾病影响,它缺乏自我修复能力。随着组织工程学的发展,通过移植与天然软骨特性紧密匹配的工程化软骨来修复软骨缺损已成为治疗软骨疾病的新选择。工程化软骨临床应用的主要障碍是如何以可靠的方式开发用于大规模生产的功能性软骨构建体。最近,实验室已培育出令人印象深刻的透明软骨,其可能具有为未来治疗大面积软骨损伤提供能力的潜力。体外构建功能性软骨的关键是确定合适的机械刺激。首先,它们应确保代谢功能,因为机械刺激在AC代谢中起到血管的作用,例如获取营养和清除废物。其次,它们应模拟滑膜关节的运动并产生表型正确的组织,以实现微观和宏观结构与功能之间的适应性发育。在本文中,我们根据生物反应器中不同介质传递的力将机械刺激分为三种类型,即通过液体介质、固体介质或其他介质传递的力,然后我们回顾并总结软骨组织工程(CTE)生物反应器的研究现状,主要关注各种机械刺激对工程化软骨的影响。基于目前的研究,膝关节存在几种运动模式;但压缩、拉伸、剪切、流体剪切或静水压力各自仅部分反映体内的力学状况。在本研究中,我们提出滚动 - 滑动 - 压缩载荷包含多种刺激,在CTE中能更好地代表力学环境。此外,工程师们常常忽视生化因素对工程化软骨生长和发育的重要性。在我们看来,只有充分考虑机械和生化因素的协同作用,才能找到功能性软骨构建体的合适培养条件。再次强调,在适当的生化条件下,滚动 - 滑动 - 压缩载荷可能有助于在体外实现工程化软骨结构与功能之间的适应性发育。

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