Advertisement

Biomechanics and Modeling in Mechanobiology

, Volume 14, Issue 2, pp 231–243 | Cite as

Multiscale fluid–structure interaction modelling to determine the mechanical stimulation of bone cells in a tissue engineered scaffold

  • Feihu Zhao
  • Ted J. Vaughan
  • Laoise M. Mcnamara
Original Paper

Abstract

Recent studies have shown that mechanical stimulation, by means of flow perfusion and mechanical compression (or stretching), enhances osteogenic differentiation of mesenchymal stem cells and bone cells within biomaterial scaffolds in vitro. However, the precise mechanisms by which such stimulation enhances bone regeneration is not yet fully understood. Previous computational studies have sought to characterise the mechanical stimulation on cells within biomaterial scaffolds using either computational fluid dynamics or finite element (FE) approaches. However, the physical environment within a scaffold under perfusion is extremely complex and requires a multiscale and multiphysics approach to study the mechanical stimulation of cells. In this study, we seek to determine the mechanical stimulation of osteoblasts seeded in a biomaterial scaffold under flow perfusion and mechanical compression using multiscale modelling by two-way fluid–structure interaction and FE approaches. The mechanical stimulation, in terms of wall shear stress (WSS) and strain in osteoblasts, is quantified at different locations within the scaffold for cells of different attachment morphologies (attached, bridged). The results show that 75.4 % of scaffold surface has a WSS of 0.1–10 mPa, which indicates the likelihood of bone cell differentiation at these locations. For attached and bridged osteoblasts, the maximum strains are 397 and 177,200 \(\upmu \) \(\upvarepsilon \), respectively. Additionally, the results from mechanical compression show that attached cells are more stimulated (\(\mathrm{maximum\,strain}=22,600\,\upmu \) \(\upvarepsilon \)) than bridged cells (\(\mathrm{maximum\,strain}=10,000\,\upmu \) \(\upvarepsilon \)). Such information is important for understanding the biological response of osteoblasts under in vitro stimulation. Finally, a combination of perfusion and compression of a tissue engineering scaffold is suggested for osteogenic differentiation.

Keywords

Fluid–structure interaction Multiscale modelling  Osteoblast Tissue engineered scaffold 

Notes

Acknowledgments

The authors would like to acknowledge the funding provided by the European Research Council (ERC) under Grant Number 258992 (BONEMECHBIO). In addition, the first author wishes to express his gratitude to Dr. S. W. Verbruggen (Biomedical Engineering, National University of Ireland, Galway) for his help with model generation.

References

  1. Adachi T, Aonuma Y, Tanaka M, Takano-Yamamoto T, Kamioka H (2009) Calcium response in single osteocytes to locally applied mechanical stimulus: differences in cell process and cell body. J Biomech 42(12):1989–1995. doi: 10.1016/j.jbiomech.2009.04.034 CrossRefGoogle Scholar
  2. Anderson EJ, Falls TD, Sorkin AM, Knothe Tate ML (2006) The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction. Biomed Eng Online 5:27. doi: 10.1186/1475-925X-5-27 CrossRefGoogle Scholar
  3. Bacabac RG, Smit TH, Mullender MG, Dijcks SJ, Van Loon JJWA, Klein-Nulend J (2004) Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem Biophys Res Commun 315(4):823–829. doi: 10.1016/j.bbrc.2004.01.138 CrossRefGoogle Scholar
  4. Ban Y, Wu YY, Yu T, Geng N, Wang YY, Liu XG, Gong P (2011) Response of osteoblasts to low fluid shear stress is time dependent. Tissue Cell 43(5):311–317. doi: 10.1016/j.tice.2011.06.003 CrossRefGoogle Scholar
  5. Bancroft GN, Sikavitsas VI, van den Dolder J, Sheffield TL, Ambrose CG, Jansen JA, Mikos AG (2002) Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc Natl Acad Sci USA 99(20):12600–12605. doi: 10.1073/pnas.202296599 CrossRefGoogle Scholar
  6. Blecha LD, Rakotomanana L, Razafimahery F, Terrier A, Pioletti DP (2010) Mechanical interaction between cells and fluid for bone tissue engineering scaffold: modulation of the interfacial shear stress. J Biomech 43(5):933–937. doi: 10.1016/j.jbiomech.2009.11.004 CrossRefGoogle Scholar
  7. Birmingham E, Grogan JA, Niebur GL, McNamara LM, McHugh PE (2013) Computational modelling of the mechanics of trabecular bone and marrow using fluid structure interaction techniques. Ann Biomed Eng 41(4):814–826. doi: 10.1007/s10439-012-0714-1 CrossRefGoogle Scholar
  8. 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(36):5544–5554. doi: 10.1016/j.biomaterials.2007.09.003 CrossRefGoogle Scholar
  9. Freyman TM, Yannas IV, Pek Y-S, Yokoo R, Gibson LJ (2001) Micromechanics of fibroblast contraction of a collagen–GAG matrix. Exp Cell Res 269(1):140–153. doi: 10.1006/excr.2001.5302 CrossRefGoogle Scholar
  10. Goldstein AS, Juarez TM, Helmke D, Gustin MC, Mikos AG (2001) Effect of convection on osteoblastic cell growth and function in biodegradable polymer foam scaffold. Biomaterials 22(11):1279–1288. doi: 10.1016/S0142-9612(00)00280-5 CrossRefGoogle Scholar
  11. Gomes ME, Sikavitasa VI, Behravesh E, Reis RL, Mikos AG (2003) Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells cultured on starch-based three dimensional scaffolds. J Biomed Mater Res A 67(1):87–95. doi: 10.1002/jbm.a.10075 CrossRefGoogle Scholar
  12. Jaasma MJ, Plunkett NA, O’Brien FJ (2008) Design and validation of a dynamic flow perfusion bioreactor for use with compliant tissue engineering scaffolds. J Biotechnol 133(4):490–496. doi: 10.1016/j.jbiotec.2007.11.010 CrossRefGoogle Scholar
  13. Juhasz T, Matta C, Somogyi C, Katona E, Takacs R, Soha RF, Szabo IA, Cserhati C, Szody R, Karacsonyi Z, Bako E, Gergely P, Zakany R (2014) Mechanical loading stimulates chondrogenesis visa the PKA/CREB-Sox9 and PP2A pathways in chicken micromass cultures. Cell Signal 26(3):468–482. doi: 10.1016/j.cellsig.2013.12.001 CrossRefGoogle Scholar
  14. Jungreuthmayer C, Jaasma MJ, Al-Munajjed AA, Zanghellini J, Kelly DJ, O’Brien FJ (2009) Deformation simulation of cells seeded on a collagen–GAG scaffold in a flow perfusion bioreactor using a sequential 3D CFD-elastostatics model. Med Eng Phys 31(4):420–427. doi: 10.1016/j.medengphy.2008.11.003 CrossRefGoogle Scholar
  15. Keogh MB, Partap S, Daly JS, O’Brien FJ (2011) Three hours of perfusion culture prior to 28 days of static culture, enhances osteogenesis by human cells in a collagen–GAG scaffold. Biotechnol Bioeng 108(5):1203–1210. doi: 10.1002/bit.23032 CrossRefGoogle Scholar
  16. Kim K, Yeatts A, Dean D, Fisher JP (2010) Stereolithographic bone scaffold design parameters: osteogenic differentiation and signal expression. Tissue Eng Part B Rev 16(5):523–539. doi: 10.1089/ten.TEB.2010.0171 CrossRefGoogle Scholar
  17. Klein-Nulend J, van der Plas A, Semeins CM, Ajubi NE, Frangos JA, Nijweide PJ, Burger EH (1995) Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J 9(5):441–445Google Scholar
  18. Li D, Tang T, Lu J, Dai K (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 Part A 15(10):2773–2783. doi: 10.1089/ten.TEA.2008.0540 CrossRefGoogle Scholar
  19. Li M, Liu W, Sun J, Xianyu Y, Wang J, Zhang W, Zheng W, Huang D, Di S, Long YZ, Jiang X (2013) Culturing primary human osteoblasts on electrospum Poly(lactic-co-glycolic acid) and Poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering. ACS Appl Mater Interfaces 5(13):5921–5926. doi: 10.1021/am401937m CrossRefGoogle Scholar
  20. Liu L, Yu B, Chen J, Tang Z, Zong C, Shen D, Zheng Q, Tong X, Gao C, Wang J (2012) Different effects of intermittent and continuous fluid shear stresses on osteogenic differentiation of human mesenchymal stem cells. Biomech Model Mechanobiol 11(3–4):391–401. doi: 10.1007/s10237-011-0319-x CrossRefGoogle Scholar
  21. Lupu-Haber Y, Pinkas O, Boehm S, Scheper T, Kasper C, Machluf M (2013) Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration. Biomed Microdevices 15(6):1055–1066. doi: 10.1007/s10544-013-9797-1 CrossRefGoogle Scholar
  22. Lyons FG, Al-Munajjed AA, Kieran SM, Toner ME, Murphy CM, Duffy GP, O’Brien FJ (2010) The healing of bony defects by cell-free collagen-based scaffolds compared to stem cells-seeded tissue engineered constructs. Biomaterials 31(35):9232–9243. doi: 10.1016/j.biomaterials.2010.08.056 CrossRefGoogle Scholar
  23. McCoy RJ, Jungreuthmayer C, O’Brien FJ (2012) Influence of flow rate and scaffold pore size on cell behaviour during mechanical stimulation in a flow perfusion bioreactor. Biotechnol Bioeng 109(6):1583–1594. doi: 10.1002/bit.24424 CrossRefGoogle Scholar
  24. Milan JL, Planell JA, Lacroix D (2009) Computational modelling of the mechanical environment of osteogenesis within a polylactic acid–calcium phosphate glass scaffold. Biomaterials 30(25):4219–4226. doi: 10.1016/j.biomaterials.2009.04.026 CrossRefGoogle Scholar
  25. Olivares AL, Marsal E, Planell JA, Lacroix D (2009) Finite element study of scaffold architecture design and culture conditions for tissue engineering. Biomaterials 30(30):6142–6149. doi: 10.1016/j.biomaterials.2009.07.041 CrossRefGoogle Scholar
  26. Owan I, Burr DB, Turner CH, Qiu J, Tu J, Onyia JE, Duncan RL (1997) Mechanotransduction in bone: osteoblasts are more responsive to fluid force than mechanical strain. Am J Physiol Cell Physiol 273(3):C810–C815Google Scholar
  27. Park SH, Park DS, Shin JW, Kang YG, Kim HK, Yoon TR, Shin JW (2012) Scaffolds for bone tissue engineering fabricated from two different materials by the rapid prototyping technique: PCL versus PLGA. J Mater Sci Mater Med 23(11):2671–2678. doi: 10.1007/s10856-012-4738-8 CrossRefGoogle Scholar
  28. Prendergast PJ, Huiskes R, Søballe K (1997) Biophysical stimuli on cells during tissue differentiation at implant interfaces. J Biomech 30(6):539–548. doi: 10.1016/S00219290(96)001406
  29. Prendergast PJ, Huiskes R, Søballe K (1997) Biophysical stimuli on cells during tissue differentiation at implant interfaces. J Biomech 30(6):539–548. doi: 10.1016/S00219290(96)001406
  30. Ryan G, McGarry P, Pandit A, Apatsidis D (2009) Analysis of the mechanical behaviour of a Titanium scaffold with a repeating unit-cell substructure. J Biomed Mater Res B Appl Biomater 90(2):894–906. doi: 10.1002/jbm.b.31361 CrossRefGoogle Scholar
  31. Samavedi S, Guelcher SA, Goldstein AS, Whittington AR (2012) Response of bone marrow stromal cells to graded co-electrospun scaffolds and its implications for engineering the ligament-bone interface. Biomaterials 33(31):7727–7735. doi: 10.1016/j.biomaterials.2012.07.008 CrossRefGoogle Scholar
  32. Seliktar D, Dunkelman N, Peterson AE, Schreiber RE, Willoughby J, Naughton GK (2002) Application of shear flow stress to chondrocytes. Google Patents EP1019489 A4Google Scholar
  33. Sikavitsas VI, Bancroft GN, Lemoine JJ, Liebschner MA, Dauner M, Mikos AG (2005) Flow perfusion enhances the calcified matrix deposition of marrow stromal cells in biodegradable nonwoven fiber mesh scaffolds. Ann Biomed Eng 33(1):63–70. doi: 10.1007/s10439-005-8963-x CrossRefGoogle Scholar
  34. Sittichockechaiwut A, Scutt AM, Ryan AJ, Bonewald LF, Reilly GC (2009) Use of rapid mineralising osteoblasts and short periods of mechanical loading to accelerate matrix maturation in 3D scaffolds. Bone 44(5):822–829. doi: 10.1016/j.bone.2008.12.027 CrossRefGoogle Scholar
  35. Stops AJ, McMahon LA, O’Mahoney D, Prendergast PJ, McHugh PE (2008) A finite element prediction of strain on cells in a highly porous collagen–glycosaminoglycan scaffold. J Biomech Eng 130(6):061001. doi: 10.1115/1.2979873 CrossRefGoogle Scholar
  36. Stops AJ, Harison NM, Haugh MG, O’Brien FJ, McHugh PE (2010) Local and regional mechanical characterisation of a collagen–gycosaminoglycan scaffold using high-resolution finite element analysis. J Mech Behav Biomed Mater 3(4):292–302. doi: 10.1016/j.jmbbm.2009.12.003
  37. Sugawara Y, Ando R, Kamioka H, Ishihara Y, Murshid SA, Hashimoto K, Kataoka N, Tsujioka K, Kajiya F, Yamashiro T, TakanoYamamoto T (2008) The alteration of a mechanical property of bone cells during the process of changing from osteoblasts to osteocytes. Bone 43(1):19–24. doi: 10.1016/j.bone.2008.02.020
  38. Thompson MS, Epari DR, Bieler F, Duda GN (2010) In vitro models for bone mechanobiology: applications in bone regeneration and tissue engineering. Proc Inst Mech Eng H 224(12):1533–1541. doi: 10.1243/09544119JEIM807 CrossRefGoogle Scholar
  39. Vaughan TJ, Haugh MG, McNamara LM (2013) A fluid-structure interaction model to characterize bone cell stimulation in parallel-plate flow chamber systems. J R Soc Interface 10(81):20120900. doi: 10.1098/rsif.2012.0900 CrossRefGoogle Scholar
  40. Verbruggen SW, Vaughan TJ, McNamara LM (2012) Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes. J R Soc Interface 9(75):2735–2744. doi: 10.1098/rsif.2012.0286 CrossRefGoogle Scholar
  41. Verbruggen SW, Vaughan TJ, McNamara LM (2013) Fluid flow in the osteocyte mechanical environment: a fluid–structure interaction approach. Biomech Model Mechanobiol. doi: 10.1007/s10237-013-0487-y
  42. Vozzi G, Corallo C, Carta S, Fortina M, Gattazzo F, Galletti M, Giordano N (2013) Collagen–gelatin–genipin–hydroxyapatite composite scaffolds colonized by human primary osteoblasts are suitable for bone tissue engineering application: in vitro evidences. J Biomed Mater Res A. doi: 10.1002/jbm.a.34823
  43. Westbroek I, Ajubi NE, Alblas MJ, Semeins CM, Klein-Nulend J, Burger EH, Nijweide PJ (2000) Differential stimulation of prostaglandin G/H synthase-2 in osteocytes and other osteogenic cells by pulsating fluid flow. Biochem Biophys Res Commun 268(2):414–419. doi: 10.1006/bbrc.2000.2154 CrossRefGoogle Scholar
  44. Xie L, Zhang N, Marsano A, Vunjak-Novakovic G, Zhang Y, Lopez MJ (2013) In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold. Stem Cell Rev 9(6):858–872. doi: 10.1007/s12015-013-9456-1 CrossRefGoogle Scholar
  45. You J, Yellowley CE, Donahue HJ, Zhang Y, Chen Q, Jacobs CR (2000) Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. J Biomech Eng 122(4):387–393. doi: 10.1115/1.1287161 CrossRefGoogle Scholar
  46. Yourek G, McCormick SM, Mao JJ, Reilly GC (2010) Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen Med 5(5):713–724. doi: 10.2217/rme.10.60 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Feihu Zhao
    • 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