Chinese Medical Sciences Journal ›› 2021, Vol. 36 ›› Issue (4): 323-332.doi: 10.24920/004007

• 综述 • 上一篇    下一篇

组织工程中细胞实验和动物实验的替代计算模型

黄皓1,4,刘朝宗2,易腾3,Maryam Tamaddon2,苑姗姗5,史震云4,*(),刘子钰1,2,3,*()   

  1. 1北京航空航天大学工程医学院,北京 100191
    2英国伦敦大学学院外科与介入科学系,英国伦敦斯坦莫尔市 英国皇家国家骨科医院,伦敦HA7 4LP,英国
    3国防科技创新研究院,北京 100071
    4北京航空航天大学机械工程及自动化学院,北京 100191
    5青岛市立医院心内科,山东青岛 266071
  • 收稿日期:2021-09-27 出版日期:2021-12-31 发布日期:2022-01-06
  • 通讯作者: 史震云,刘子钰 E-mail:shichong1983623@hotmail.com;liu_ziyu@buaa.edu.cn

Substitution for In Vitro and In Vivo Tests: Computational Models from Cell Attachment to Tissue Regeneration

Hao Huang1,4,Chaozong Liu2,Teng Yi3,Maryam Tamaddon2,Shanshan Yuan5,Zhenyun Shi4,*(),Ziyu Liu1,2,3,*()   

  1. 1School of Engineering Medicine, Beihang University, 100191 Beijing, China
    2Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, Stanmore HA7 4LP, London, UK
    3National Institude of Defense Science and Technology, Beijing 100071, China
    4School of Mechanical Engineering and Automation, Beihang University, 100191 Beijing, China
    5Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong 266071, China
  • Received:2021-09-27 Published:2021-12-31 Online:2022-01-06
  • Contact: Zhenyun Shi,Ziyu Liu E-mail:shichong1983623@hotmail.com;liu_ziyu@buaa.edu.cn

摘要:

在骨科植入物和再生医学研究领域,为了得到合适的产品需要经过反复实验分析优化材料、结构、机械性能等指标,从细胞实验到临床试验的整个过程既昂贵又耗时。计算模拟方法是组织工程产品开发的设计工具,可以有效降低开发成本和时耗。本文综述了一系列组织工程模型,他们能模拟从细胞附着到组织再生的全过程。从细胞黏附到组织再生的一体化模型的建立能优化组织工程产品设计和评价过程。然而,目前模拟组织工程过程的模型均各自独立。本文重点介绍了组织工程中细胞黏附、营养物质运输和细胞增殖、分化、迁移的模型,试图将所有独立模型串联在一起以供读者使用。在细胞黏附模型中,离散相模型能最精确地模拟控制细胞运动过程,Stanton-Rutland模型能模拟细胞黏附过程。营养盐运输模型能是一种能将流体体积模型和组分传输模型耦合的数值模型,在组织工程中被应用于营养盐运移过程的预测。有限元以及随机游走算法被用于细胞增殖、分化和迁移的模拟。大多数模型的准确性和有效性还有待进一步研究证实。由于尚缺乏检测营养物质扩散速率的技术,在凝血领域模型分析方法的研究尤其少。因此,组织工程全过程建模方法的研究还有很多工作要做。在未来,数值模型将被视为研究组织工程产品生物性能的最佳方法,并能够优化组织工程产品的参数和材料类型。

关键词: 组织工程, 支架, 计算机辅助设计, 计算流体力学, 有限元模型

Abstract:

To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trial-and-error analyses to investigate suitable product’s material, structure, mechanical properites etc. The whole process from in vivo tests to clinical trials is expensive and time-consuming. Computational model is seen as a useful analysis tool to make the product development. A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed. The challenging is that models for simulating tissue engineering processes are developed separately. From cell to tissue regeneration, it would go through blood injection after moving out the defect; to cell disperse and attach on the scaffold; to proliferation, migration and differentiation; and to the final part—becoming mature tissues. This paper reviewed models that related to tissue engineering process, aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process. This article focuses on the model analysis methods of cell adhesion, nutrient transport and cell proliferation, differentiation and migration in tissue engineering. In cell adhesion model, one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment. As for nutrient transport model, numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process. For cell proliferation, differentiation and migration, finite element method with random-walk algorithm is one the most advanced way to simulate these processes. Most of the model analysis methods require further experiments to verify the accuracy and effectiveness. Due to the lack of technology to detect the rate of nutrient diffusion, there are especially few researches on model analysis methods in the area of blood coagulation. Therefore, there is still a lot of work to be done in the research of the whole process model method of tissue engineering. In the future, the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.

Key words: tissue engineering, scaffold, computer aided design, computational fluid dynamics, finite element models

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