Advertisement

Biomechanics and Modeling in Mechanobiology

, Volume 17, Issue 1, pp 5–18 | Cite as

In silico study of bone tissue regeneration in an idealised porous hydrogel scaffold using a mechano-regulation algorithm

  • Feihu Zhao
  • Myles J. Mc Garrigle
  • Ted J. Vaughan
  • Laoise M. McNamara
Original Paper

Abstract

Mechanical stimulation, in the form of fluid perfusion or mechanical strain, enhances osteogenic differentiation and overall bone tissue formation by mesenchymal stems cells cultured in biomaterial scaffolds for tissue engineering applications. In silico techniques can be used to predict the mechanical environment within biomaterial scaffolds, and also the relationship between bone tissue regeneration and mechanical stimulation, and thereby inform conditions for bone tissue engineering experiments. In this study, we investigated bone tissue regeneration in an idealised hydrogel scaffold using a mechano-regulation model capable of predicting tissue differentiation, and specifically compared five loading cases, based on known experimental bioreactor regimes. These models predicted that low levels of mechanical loading, i.e. compression (0.5% strain), pore pressure of 10 kPa and a combination of compression (0.5%) and pore pressure (10 kPa), could induce more osteogenic differentiation and lead to the formation of a higher bone tissue fraction. In contrast greater volumes of cartilage and fibrous tissue fractions were predicted under higher levels of mechanical loading (i.e. compression strain of 5.0% and pore pressure of 100 kPa). The findings in this study may provide important information regarding the appropriate mechanical stimulation for in vitro bone tissue engineering experiments.

Keywords

In silico bone tissue engineering Mechanical stimulation Mechano-regulation algorithm 

Notes

Acknowledgements

This study is supported by European Research Council (ERC) under the project of BONEMECHBIO (Grant No. 258992). Additionally, F. Zhao would like to thank Dr. Maria Jose Gomez-Benito (University of Zaragoza), Prof. Damien Lacroix (University of Sheffield) and Dr. Patrick McGarry (NUI Galway) for the insightful discussion. Also, Irish Centre for High End Computing (ICHEC) and MaTe Computing Cluster in Eindhoven University of Technology (Netherlands) are acknowledged for running the simulations.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests on this study.

References

  1. Albertsm B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Fibroblasts and their transformations: the connective-tissue cell family, 4th edn. Garland Science, New YorkGoogle Scholar
  2. Alsberg E, Anderson KW, Albeiruti A, Franceschi RT, Mooney DJ (2001) Cell-interactive alginate hydrogels for bone tissue engineering. J Dent Res 80:2025–2029CrossRefGoogle Scholar
  3. Bidarra SJ, Barrias CC, Barbosa MA, Soares R, Granja PL (2010) Immobilization of human mesenchymal stem cells within RGD-grafted alginate microspheres and assessment of their angiogenic potential. Biomacromolecules 11:1956–1964. doi: 10.1021/bm100264a CrossRefGoogle Scholar
  4. Bland YS, Critchlow MA, Ashhurst DE (1999) The expression of the fibrillar collagen genes during fracture healing: heterogeneity of the matrices and differentiation of the osteoprogenitor cells. Histochem J 31:797–809CrossRefGoogle Scholar
  5. Burke DP, Kelly DJ (2012) Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model. PLoS ONE 7:e40737. doi: 10.1371/journal.pone.0040737 CrossRefGoogle Scholar
  6. Byrne DP, Lacroix D, Planell JA, Kelly DJ, Prendergast PJ (2007) 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 28:5544–5554. doi: 10.1016/j.biomaterials.2007.09.003 CrossRefGoogle Scholar
  7. Carter DR, Blenman PR, Beaupre GS (1988) Correlations between mechanical stress history and tissue differentiation in initial fracture healing. J Orthop Res 6:736–748. doi: 10.1002/jor.1100060517 CrossRefGoogle Scholar
  8. Chapman LA, Shipley RJ, Whiteley JP, Ellis MJ, Byrne HM, Waters SL (2014) Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling. PLoS ONE 9:e105813. doi: 10.1371/journal.pone.0105813 CrossRefGoogle Scholar
  9. Checa S, Prendergast PJ (2010) Effect of cell seeding and mechanical loading on vascularization and tissue formation inside a scaffold: a mechano-biological model using a lattice approach to simulate cell activity. J Biomech 43:961–968CrossRefGoogle Scholar
  10. Chen PY, Yang KC, Wu CC, Yu JH, Lin FH, Sun JS (2014) Fabrication of large perfusable macroporous cell-laden hydrogel scaffolds using microbial transglutaminase. Acta Biomater 10:912–920. doi: 10.1016/j.actbio.2013.11.009 CrossRefGoogle Scholar
  11. Chippada U, Langrana N, Yurke B (2009) Complete mechanical characterization of soft media using nonspherical rods. J Appl Phys. doi: 10.1063/1.3211313 Google Scholar
  12. Claes LE, Heigele CA (1999) Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing. J Biomech 32:255–266CrossRefGoogle Scholar
  13. Delaine-Smith RM, Reilly GC (2012) Mesenchymal stem cell responses to mechanical stimuli. Muscles Ligaments Tendons J 2:169–180Google Scholar
  14. Ford JL, Robinson DE, Scammell BE (2003) The fate of soft callus chondrocytes during long bone fracture repair. J Orthop Res 21:54–61. doi: 10.1016/S0736-0266(02)00087-6 CrossRefGoogle Scholar
  15. Guyot Y, Papantoniou I, Chai YC, Van Bael S, Schrooten J, Geris L (2014) A computational model for cell/ECM growth on 3D surfaces using the level set method: a bone tissue engineering case study. Biomech Model Mechanobiol 13:1361–1371. doi: 10.1007/s10237-014-0577-5 CrossRefGoogle Scholar
  16. Guyot Y, Luyten FP, Schrooten J, Papantoniou I, Geris L (2015) A three-dimensional computational fluid dynamics model of shear stress distribution during neotissue growth in a perfusion bioreactor. Biotechnol Bioeng 112:2591–2600. doi: 10.1002/bit.25672 CrossRefGoogle Scholar
  17. Hodgskinson R, Currey JD (1992) Young’s modulus, density and material properties in cancellous bone over a large density range. J Mater Sci Mater Med 3:377–381CrossRefGoogle Scholar
  18. Huiskes R, Van Driel WD, Prendergast PJ, Soballe K (1997) A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation. J Mater Sci Mater Med 8:785–788CrossRefGoogle Scholar
  19. Hwang CM, Sant S, Masaeli M, Kachouie NN, Zamanian B, Lee SH, Khademhosseini A (2010) Fabrication of three-dimensional porous cell-laden hydrogel for tissue engineering. Biofabrication. doi: 10.1088/1758-5082/2/3/035003 Google Scholar
  20. Isaksson H, van Donkelaar CC, Huiskes R, Ito K (2008) A mechano-regulatory bone-healing model incorporating cell-phenotype specific activity. J Theor Biol 252:230–246. doi: 10.1016/j.jtbi.2008.01.030 MathSciNetCrossRefGoogle Scholar
  21. Jagodzinski M et al (2008) Influence of perfusion and cyclic compression on proliferation and differentiation of bone marrow stromal cells in 3-dimensional culture. J Biomech 41:1885–1891. doi: 10.1016/j.jbiomech.2008.04.001 CrossRefGoogle Scholar
  22. Jukes JM, Both SK, Leusink A, Sterk LM, van Blitterswijk CA, de Boer J (2008) Endochondral bone tissue engineering using embryonic stem cells. Proc Natl Acad Sci USA 105:6840–6845. doi: 10.1073/pnas.0711662105 CrossRefGoogle Scholar
  23. Kolambkar YM, Dupont KM, Boerckel JD, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE (2011) An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials 32:65–74. doi: 10.1016/j.biomaterials.2010.08.074 CrossRefGoogle Scholar
  24. Lacroix D, Prendergast PJ, Li G, Marsh D (2002) Biomechanical model to simulate tissue differentiation and bone regeneration: application to fracture healing. Med Biol Eng Comput 40:14–21CrossRefGoogle Scholar
  25. Li DQ, Tang TT, Lu JX, Dai KR (2009) Effects of flow shear stress and mass transport on the construction of a large-scale tissue-engineered bone in a perfusion bioreactor. Tissue Eng A 15:2773–2783. doi: 10.1089/ten.tea.2008.0540 CrossRefGoogle Scholar
  26. McCoy RJ, Jungreuthmayer C, O’Brien FJ (2012) Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor. Biotechnol Bioeng 109:1583–1594. doi: 10.1002/Bit.24424 CrossRefGoogle Scholar
  27. McDermott AM, Mason DE, Lin AS, Guldberg RE, Boerckel JD (2016) Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration. J Mech Behav Biomed Mater 62:169–181. doi: 10.1016/j.jmbbm.2016.05.010 CrossRefGoogle Scholar
  28. Millward-Sadler SJ, Salter DM (2004) Integrin-dependent signal cascades in chondrocyte mechanotransduction. Ann Biomed Eng 32:435–446. doi: 10.1023/B:Abme.0000017538.72511.48 CrossRefGoogle Scholar
  29. Mizuno S, Glowacki J (1996) Three-dimensional composite of demineralized bone powder and collagen for in vitro analysis of chondroinduction of human dermal fibroblasts. Biomaterials 17:1819–1825CrossRefGoogle Scholar
  30. Murphy CM, Haugh MG, O’Brien FJ (2010) The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials 31:461–466. doi: 10.1016/j.biomaterials.2009.09.063 CrossRefGoogle Scholar
  31. Myster DL, Duronio RJ (2000) To differentiate or not to differentiate? Curr Biol CB 10:R302–304CrossRefGoogle Scholar
  32. Olivares AL, Marsal E, Planell JA, Lacroix D (2009) Finite element study of scaffold architecture design and culture conditions for tissue engineering. Biomaterials 30:6142–6149. doi: 10.1016/j.biomaterials.2009.07.041 CrossRefGoogle Scholar
  33. Prendergast PJ, Huiskes R, Soballe K (1997) ESB Research Award 1996. Biophysical stimuli on cells during tissue differentiation at implant interfaces. J Biomech 30:539–548CrossRefGoogle Scholar
  34. Reina-Romo E, Gomez-Benito MJ, Garcia-Aznar JM, Dominguez J, Doblare M (2009) Modeling distraction osteogenesis: analysis of the distraction rate. Biomech Model Mechanobiol 8:323–335. doi: 10.1007/s10237-008-0138-x CrossRefGoogle Scholar
  35. Reina-Romo E, Gomez-Benito MJ, Sampietro-Fuentes A, Dominguez J, Garcia-Aznar JM (2011) Three-dimensional simulation of mandibular distraction osteogenesis: mechanobiological analysis. Ann Biomed Eng 39:35–43. doi: 10.1007/s10439-010-0166-4 CrossRefGoogle Scholar
  36. Ribeiro FO, Gomez-Benito MJ, Folgado J, Fernandes PR, Garcia-Aznar JM (2015) In silico mechano-chemical model of bone healing for the regeneration of critical defects: the effect of BMP-2. PLoS ONE 10:e0127722. doi: 10.1371/journal.pone.0127722 CrossRefGoogle Scholar
  37. Sandino C, Lacroix D (2011) A dynamical study of the mechanical stimuli and tissue differentiation within a CaP scaffold based on micro-CT finite element models. Biomech Model Mechanobiol 10:565–576. doi: 10.1007/s10237-010-0256-0 CrossRefGoogle Scholar
  38. Sandino C, Checa S, Prendergast PJ, Lacroix D (2010) Simulation of angiogenesis and cell differentiation in a CaP scaffold subjected to compressive strains using a lattice modeling approach. Biomaterials 31:2446–2452CrossRefGoogle Scholar
  39. Sanz-Herrera JA, Garcia-Aznar JM, Doblare M (2008) A mathematical model for bone tissue regeneration inside a specific type of scaffold. Biomech Model Mechanobiol 7:355–366. doi: 10.1007/s10237-007-0089-7 CrossRefGoogle Scholar
  40. Shav D, Einav S (2010) The effect of mechanical loads in the differentiation of precursor cells into mature cells. Ann NY Acad Sci 1188:25–31. doi: 10.1111/j.1749-6632.2009.05079.x CrossRefGoogle Scholar
  41. Stops AJ, Heraty KB, Browne M, O’Brien FJ, McHugh PE (2010) A prediction of cell differentiation and proliferation within a collagen-glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow. J Biomech 43:618–626. doi: 10.1016/j.jbiomech.2009.10.037 CrossRefGoogle Scholar
  42. Yates KE (2004) Demineralized bone alters expression of Wnt network components during chondroinduction of post-natal fibroblasts. Osteoarthr Cartil OARS Osteoarthr Res Soc 12:497–505. doi: 10.1016/j.joca.2004.02.009 CrossRefGoogle Scholar
  43. Zhao F, Vaughan TJ, McNamara LM (2015) Multiscale fluid-structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold. Biomech Model Mechanobiol 14:231–243. doi: 10.1007/s10237-014-0599-z
  44. Zhao F, Vaughan TJ, McNamara LM (2016) Quantification of fluid shear stress in bone tissue engineering scaffolds with spherical and cubical pore architectures. Biomech Model Mechanobiol 15:561–577. doi: 10.1007/s10237-015-0710-0 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Feihu Zhao
    • 1
  • Myles J. Mc Garrigle
    • 1
  • Ted J. Vaughan
    • 1
  • Laoise M. McNamara
    • 1
  1. 1.Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and InformaticsNational University of IrelandGalwayIreland

Personalised recommendations