组织工程中细胞实验和动物实验的替代计算模型

黄皓; 刘朝宗; 易腾; Maryam Tamaddon; 苑姗姗; 史震云; 刘子钰

doi:10.24920/004007

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组织工程中细胞实验和动物实验的替代计算模型

中国医学科学杂志（英文版） 2021年36卷第4期页码：323-332

Reviews | Updated：2024-04-10

- 组织工程中细胞实验和动物实验的替代计算模型
- Affiliations：
  
  1. 1School of Engineering Medicine, Beihang University, 100191 Beijing, China
  2. 2Division of Surgery & Interventional Science, University College London, Royal National Orthopaedic Hospital, Stanmore HA7 4LP, London, UK
  3. 3National Institude of Defense Science and Technology, Beijing 100071, China
  4. 4School of Mechanical Engineering and Automation, Beihang University, 100191 Beijing, China
  5. 5Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong 266071, China
- Author bio：
  
  Zhenyun Shi, shichong1983623@hotmail.com
  *Ziyu Liu, liu_ziyu@buaa.edu.cn;
- Funds：
  
  Versus Arthritis Research UK(21977);European Commission via a H2020-MSCA-RISE programme(BAMOS, Grant No: 734156);Innovative UK via Newton Fund(102872);Engineering and Physical Science Research Council (EPSRC) via DTP CASE programme(EP/T517793/1)
- DOI：10.24920/004007
  中图分类号：
- 收稿日期：2021-09-27，
  
  网络出版日期：2021-12-21，
  
  纸质出版日期：2021-12-31
- Accepted：
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黄皓, 刘朝宗, 易腾, 等. 组织工程中细胞实验和动物实验的替代计算模型[J]. 中国医学科学杂志（英文版）, 2021,36(4):323-332.

Huang Hao, Liu Chaozong, Yi Teng, et al. Substitution for In Vitro and In Vivo Tests: Computational Models from Cell Attachment to Tissue Regeneration[J]. Chinese medical sciences journal, 2021, 36(4): 323-332.
黄皓, 刘朝宗, 易腾, 等. 组织工程中细胞实验和动物实验的替代计算模型[J]. 中国医学科学杂志（英文版）, 2021,36(4):323-332. DOI： 10.24920/004007.

Huang Hao, Liu Chaozong, Yi Teng, et al. Substitution for In Vitro and In Vivo Tests: Computational Models from Cell Attachment to Tissue Regeneration[J]. Chinese medical sciences journal, 2021, 36(4): 323-332. DOI： 10.24920/004007.

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。

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.

关键词

Keywords

references

Kang H , Zeng Y , Varghese S . Functionally graded multilayer scaffolds for in vivo osteochondral tissue engineering . Acta Biomater 2018 ; 78 : 365 - 77 . doi: 10.1016/j.actbio.2018.07.039 https://dx.doi.org/10.1016/j.actbio.2018.07.039 . DOI: 10.1016/j.actbio.2018.07.039 http://doi.org/10.1016/j.actbio.2018.07.039 https://linkinghub.elsevier.com/retrieve/pii/S1742706118304331 https://linkinghub.elsevier.com/retrieve/pii/S1742706118304331

Nooeaid P , Salih V , Beier JP , et al . Osteochondral tissue engineering: scaffolds, stem cells and applications . J Cell Mol Med 2012 ; 16 ( 10 ): 2247 - 70 . doi: 10.1111/j.1582-4934.2012.01571.x https://dx.doi.org/10.1111/j.1582-4934.2012.01571.x . DOI: 10.1111/j.1582-4934.2012.01571.x http://doi.org/10.1111/j.1582-4934.2012.01571.x https://onlinelibrary.wiley.com/doi/10.1111/j.1582-4934.2012.01571.x https://onlinelibrary.wiley.com/doi/10.1111/j.1582-4934.2012.01571.x

Yang PJ , Temenoff JS . Engineering orthopedic tissue interfaces . Tissue Eng Part B Rev 2009 ; 15 ( 2 ): 127 - 41 . doi: 10.1089/ten.teb.2008.0371 https://dx.doi.org/10.1089/ten.teb.2008.0371 . DOI: 10.1089/ten.teb.2008.0371 http://doi.org/10.1089/ten.teb.2008.0371 https://www.liebertpub.com/doi/10.1089/ten.teb.2008.0371 https://www.liebertpub.com/doi/10.1089/ten.teb.2008.0371

Hunziker EB . Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects . Osteoarthritis Cartilage 2002 ; 10 ( 6 ): 432 - 63 . doi: 10.1053/joca.2002.0801 https://dx.doi.org/10.1053/joca.2002.0801 . DOI: 10.1053/joca.2002.0801 http://doi.org/10.1053/joca.2002.0801 https://linkinghub.elsevier.com/retrieve/pii/S1063458402908010 https://linkinghub.elsevier.com/retrieve/pii/S1063458402908010

Xu S , Du P , Xie Y , et al . Cell distribution in a scaffold with random architectures under the influence of fluid dynamics . J Biomater Appl 2008 ; 23 ( 3 ): 229 - 45 . doi: 10.1177/0885328207086322 https://dx.doi.org/10.1177/0885328207086322 . DOI: 10.1177/0885328207086322 http://doi.org/10.1177/0885328207086322 http://journals.sagepub.com/doi/10.1177/0885328207086322 http://journals.sagepub.com/doi/10.1177/0885328207086322

Olivares AL , Lacroix D . Simulation of cell seeding within a three-dimensional porous scaffold: a fluid-particle analysis . Tissue Eng Part C Methods 2012 ; 18 ( 8 ): 624 - 31 . doi: 10.1089/ten.TEC.2011.0660 https://dx.doi.org/10.1089/ten.TEC.2011.0660 . DOI: 10.1089/ten.TEC.2011.0660 http://doi.org/10.1089/ten.TEC.2011.0660 https://www.liebertpub.com/doi/10.1089/ten.tec.2011.0660 https://www.liebertpub.com/doi/10.1089/ten.tec.2011.0660

Prendergast PJ , Huiskes R , Søballe K . ESB Research Award 1996. Biophysical stimuli on cells during tissue differentiation at implant interfaces . J Biomech 1997 ; 30 ( 6 ): 539 - 48 . doi: 10.1016/s0021-9290(96)00140-6 https://dx.doi.org/10.1016/s0021-9290(96)00140-6 . DOI: 10.1016/s0021-9290(96)00140-6 http://doi.org/10.1016/s0021-9290(96)00140-6

Byrne DP , Lacroix D , Planell JA , et al . Simulation of tissue differentiation in a scaffold as a function of porosity, Young’s modulus and dissolution rate: application of mechanobiological models in tissue engineering . Biomaterials 2007 ; 28 ( 36 ): 5544 - 54 . doi: 10.1016/j.biomaterials.2007.09.003 https://dx.doi.org/10.1016/j.biomaterials.2007.09.003 . DOI: 10.1016/j.biomaterials.2007.09.003 http://doi.org/10.1016/j.biomaterials.2007.09.003 https://linkinghub.elsevier.com/retrieve/pii/S0142961207007120 https://linkinghub.elsevier.com/retrieve/pii/S0142961207007120

Liu Z , Tamaddon M , Chen SM , et al . Determination of an initial stage of the bone tissue ingrowth into titanium matrix by cell adhesion model . Front Bioeng Biotechnol 2021 ; 9 : 736063 . doi: 10.3389/fbioe.2021.736063 https://dx.doi.org/10.3389/fbioe.2021.736063 . DOI: 10.3389/fbioe.2021.736063 http://doi.org/10.3389/fbioe.2021.736063 https://www.frontiersin.org/articles/10.3389/fbioe.2021.736063/full https://www.frontiersin.org/articles/10.3389/fbioe.2021.736063/full

Liu J , Chen G , Xu H , et al . Pre-vascularization in fibrin Gel/PLGA microsphere scaffolds designed for bone regeneration . NPG Asia Materials 2018 ; 10 ( 8 ): 827 - 39 . doi: 10.1038/s41427-018-0076-8 https://dx.doi.org/10.1038/s41427-018-0076-8 . DOI: 10.1038/s41427-018-0076-8 http://doi.org/10.1038/s41427-018-0076-8 https://doi.org/10.1038/s41427-018-0076-8 https://doi.org/10.1038/s41427-018-0076-8

Daley WP , Peters SB , Larsen M . Extracellular matrix dynamics in development and regenerative medicine . J Cell Sci 2008 ; 121 ( Pt 3 ): 255 - 64 . doi: 10.1242/jcs.006064 https://dx.doi.org/10.1242/jcs.006064 . DOI: 10.1242/jcs.006064 http://doi.org/10.1242/jcs.006064 https://journals.biologists.com/jcs/article/121/3/255/30425/Extracellular-matrix-dynamics-in-development-and https://journals.biologists.com/jcs/article/121/3/255/30425/Extracellular-matrix-dynamics-in-development-and

Liu Z , Tamaddon M , Gu Y , et al . Cell seeding process experiment and simulation on three-dimensional polyhedron and cross-link design scaffolds . Front Bioeng Biotechnol 2020 ; 8 : 104 . doi: 10.3389/fbioe.2020.00104 https://dx.doi.org/10.3389/fbioe.2020.00104 . DOI: 10.3389/fbioe.2020.00104 http://doi.org/10.3389/fbioe.2020.00104 https://www.frontiersin.org/article/10.3389/fbioe.2020.00104/full https://www.frontiersin.org/article/10.3389/fbioe.2020.00104/full

Ali F , Taresh S , Al-Nuzaily M , et al . Stem cells differentiation and probing their therapeutic applications in hematological disorders: a critical review . Eur Rev Med Pharmacol Sci 2016 ; 20 ( 20 ): 4390 - 400 . doi: 10.1155/2016/7653489 https://dx.doi.org/10.1155/2016/7653489 . DOI: 10.1155/2016/7653489 http://doi.org/10.1155/2016/7653489

Santoro R , Olivares AL , Brans G , et al . Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing . Biomaterials 2010 ; 31 ( 34 ): 8946 - 52 . doi: 10.1016/j.biomaterials.2010.08.009 https://dx.doi.org/10.1016/j.biomaterials.2010.08.009 . DOI: 10.1016/j.biomaterials.2010.08.009 http://doi.org/10.1016/j.biomaterials.2010.08.009 https://linkinghub.elsevier.com/retrieve/pii/S014296121001015X https://linkinghub.elsevier.com/retrieve/pii/S014296121001015X

Wendt D , Stroebel S , Jakob M , et al . Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions . Biorheology 2006 ; 43 ( 3, 4 ): 481 - 8 .

Cherry EM , JK Eaton . Shear thinning effects on blood flow in straight and curved tubes . Phys FLUIDS 2013 ; 25 : 0733104 . doi: 10.1063/1.4816369 https://dx.doi.org/10.1063/1.4816369 . DOI: 10.1063/1.4816369 http://doi.org/10.1063/1.4816369

Reymond P , Perren F , Lazeyras F , et al . Patient-specific mean pressure drop in the systemic arterial tree, a comparison between 1-D and 3-D models . J Biomech 2012 ; 45 ( 15 ): 2499 - 505 . doi: 10.1016/j.jbiomech.2012.07.020 https://dx.doi.org/10.1016/j.jbiomech.2012.07.020 . DOI: 10.1016/j.jbiomech.2012.07.020 http://doi.org/10.1016/j.jbiomech.2012.07.020 https://linkinghub.elsevier.com/retrieve/pii/S0021929012004174 https://linkinghub.elsevier.com/retrieve/pii/S0021929012004174

Truscello S , Kerckhofs G , Van Bael S , et al . Prediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study . Acta Biomater 2012 ; 8 ( 4 ): 1648 - 58 . doi: 10.1016/j.actbio.2011.12.021 https://dx.doi.org/10.1016/j.actbio.2011.12.021 . DOI: 10.1016/j.actbio.2011.12.021 http://doi.org/10.1016/j.actbio.2011.12.021

Xiang J , Tremmel M , Kolega J , et al . Newtonian viscosity model could overestimate wall shear stress in intracranial aneurysm domes and underestimate rupture risk . J Neurointerv Surg 2012 ; 4 ( 5 ): 351 - 7 . doi: 10.1136/neurintsurg-2011-010089 https://dx.doi.org/10.1136/neurintsurg-2011-010089 . DOI: 10.1136/neurintsurg-2011-010089 http://doi.org/10.1136/neurintsurg-2011-010089 http://jnis.bmj.com/lookup/doi/10.1136/neurintsurg-2011-010089 http://jnis.bmj.com/lookup/doi/10.1136/neurintsurg-2011-010089

Jiang Y , Zhang J , Zhao W . Effects of the inlet conditions and blood models on accurate prediction of hemodynamics in the stented coronary arteries . AIP Adv 2015 ; 5 ( 5 ): 057109 . doi: 10.1063/1.4919937 https://dx.doi.org/10.1063/1.4919937 . DOI: 10.1063/1.4919937 http://doi.org/10.1063/1.4919937 http://aip.scitation.org/doi/10.1063/1.4919937 http://aip.scitation.org/doi/10.1063/1.4919937

Koch MA , Vrij EJ , Engel E , et al . Perfusion cell seeding on large porous PLA/calcium phosphate composite scaffolds in a perfusion bioreactor system under varying perfusion parameters . J Biomed Mater Res A 2010 ; 95 ( 4 ): 1011 - 8 . doi: 10.1002/jbm.a.32927 https://dx.doi.org/10.1002/jbm.a.32927 . DOI: 10.1002/jbm.a.32927 http://doi.org/10.1002/jbm.a.32927

Wendt D , Marsano A , Jakob M , et al . Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity . Biotechnol Bioeng 2003 ; 84 ( 2 ): 205 - 14 . doi: 10.1002/bit https://dx.doi.org/10.1002/bit . DOI: 10.1002/bit http://doi.org/10.1002/bit

Stanton DW , CJ Rutland . Modeling fuel film formation and wall interaction in diesel engines . SAE Trans 1996 ; 808 - 24 . doi: 10.4271/960628 https://dx.doi.org/10.4271/960628 . DOI: 10.4271/960628 http://doi.org/10.4271/960628

O’rourke PJ , Amsden AA . A particle numerical model for wall film dynamics in port-injected engines. SAE Technical Paper Series . Detroit: SAE ; 1996 . p. 2000 - 13 .

O’Rourke PJ , Amsden AA . A spray/wall interaction submodel for the KIVA-3 wall film model. SAE Technical Paper Series . Detroit: SAE ; 2000 . p. 281 - 98 . doi: 10.4271/2000-01-0271 https://dx.doi.org/10.4271/2000-01-0271 . DOI: 10.4271/2000-01-0271 http://doi.org/10.4271/2000-01-0271

Karande TS , Ong JL , Agrawal CM . Diffusion in musculoskeletal tissue engineering scaffolds: design issues related to porosity, permeability, architecture, and nutrient mixing . Ann Biomed Eng 2004 ; 32 ( 12 ): 1728 - 43 . doi: 10.1007/s10439-004-7825-2 https://dx.doi.org/10.1007/s10439-004-7825-2 . DOI: 10.1007/s10439-004-7825-2 http://doi.org/10.1007/s10439-004-7825-2

Makhaniok A , Haranava Y , Goranov V , et al . In silico prediction of the cell proliferation in porous scaffold using model of effective pore . Biosystems 2013 ; 114 ( 3 ): 227 - 37 . doi: 10.1016/j.biosystems.2013. 10.001 https://dx.doi.org/10.1016/j.biosystems.2013. 10.001 . DOI: 10.1016/j.biosystems.2013.10.001 http://doi.org/10.1016/j.biosystems.2013.10.001

Dunn JC , Chan WY , Cristini V , et al . Analysis of cell growth in three-dimensional scaffolds . Tissue Eng 2006 ; 12 ( 4 ): 705 - 16 . doi: 10.1089/ten.2006.12.705 https://dx.doi.org/10.1089/ten.2006.12.705 . DOI: 10.1089/ten.2006.12.705 http://doi.org/10.1089/ten.2006.12.705 https://www.liebertpub.com/doi/10.1089/ten.2006.12.705 https://www.liebertpub.com/doi/10.1089/ten.2006.12.705

Rouwkema J , Koopman B , Blitterswijk C , et al . Supply of nutrients to cells in engineered tissues . Biotechnol Genet Eng Rev 2010 ; 26 : 163 - 78 . doi: 10.5661/bger-26-163 https://dx.doi.org/10.5661/bger-26-163 . DOI: 10.5661/bger-26-163 http://doi.org/10.5661/bger-26-163

Reynolds M , McCann SR . Human marrow stromal cells in short-term semi-solid bone marrow culture in aplastic anaemia . Scand J Haematol 1985 ; 34 ( 2 ): 101 - 10 . doi: 10.1111/j.1600-0609.1985.tb02241.x https://dx.doi.org/10.1111/j.1600-0609.1985.tb02241.x . DOI: 10.1111/j.1600-0609.1985.tb02241.x http://doi.org/10.1111/j.1600-0609.1985.tb02241.x

Winterton RHS . Thermal design of nuclear reactors . Elsevier ; 1981 . Available from: https://doi.org/10.1016/B978-0-08-024215-6.50003-6 https://dx.doi.org/10.1016/B978-0-08-024215-6.50003-6 . DOI: https://doi.org/10.1016/B978-0-08-024215-6.50003-6 http://doi.org/https://doi.org/10.1016/B978-0-08-024215-6.50003-6

Botchwey EA , Dupree MA , Pollack SR , et al . Tissue engineered bone: measurement of nutrient transport in three-dimensional matrices . J Biomed Mater Res A 2003 ; 67 ( 1 ): 357 - 67 . doi: 10.1002/jbm.a.10111 https://dx.doi.org/10.1002/jbm.a.10111 . DOI: 10.1002/jbm.a.10111 http://doi.org/10.1002/jbm.a.10111

Mofrad AZ , Mashayekhan S , Bastani D . Simulation of the effects of oxygen carriers and scaffold geometry on oxygen distribution and cell growth in a channeled scaffold for engineering myocardium . Math Biosci 2017 ; 294 : 160 - 71 . doi: 10.1016/j.mbs.2017.09.003 https://dx.doi.org/10.1016/j.mbs.2017.09.003 . DOI: 10.1016/j.mbs.2017.09.003 http://doi.org/10.1016/j.mbs.2017.09.003 https://linkinghub.elsevier.com/retrieve/pii/S0025556417302468 https://linkinghub.elsevier.com/retrieve/pii/S0025556417302468

Pérez MA , Prendergast PJ . Random-walk models of cell dispersal included in mechanobiological simulations of tissue differentiation . J Biomech 2007 ; 40 ( 10 ): 2244 - 53 . doi: 10.1016/j.jbiomech.2006.10.020 https://dx.doi.org/10.1016/j.jbiomech.2006.10.020 . DOI: 10.1016/j.jbiomech.2006.10.020 http://doi.org/10.1016/j.jbiomech.2006.10.020

Søballe K , Hansen ES , B-Rasmussen H , et al . Tissue ingrowth into titanium and hydroxyapatite-coated implants during stable and unstable mechanical conditions . J Orthop Res 1992 ; 10 ( 2 ): 285 - 99 . doi: 10.1002/jor.1100100216 https://dx.doi.org/10.1002/jor.1100100216 . DOI: 10.1002/jor.1100100216 http://doi.org/10.1002/jor.1100100216

Lanza R , Gearhart J , Hogan B , et al . Essentials of stem cell biology . Elsevier ; 2009 . Available from: https://doi.org/10.1016/C2009-0-00078-6 https://dx.doi.org/10.1016/C2009-0-00078-6 . DOI: https://doi.org/10.1016/C2009-0-00078-6 http://doi.org/https://doi.org/10.1016/C2009-0-00078-6

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