Annals of Biomedical Engineering

, Volume 42, Issue 6, pp 1319–1330 | Cite as

Modeling Pressure Drop Using Generalized Scaffold Characteristics in an Axial-Flow Bioreactor for Soft Tissue Regeneration

  • Jagdeep T. Podichetty
  • Prasana R. Bhaskar
  • Abdurizzagh Khalf
  • Sundararajan V. Madihally
Article

Abstract

The goal of this study was to better understand how analytical permeability models based on scaffold architecture can facilitate a non-invasive technique to real time monitoring of pressure drop in bioreactors. In particular, we evaluated the permeability equations for electrospun and freeze dried scaffolds via pressure drop comparison in an axial-flow bioreactor using computational fluid dynamic (CFD) and experimentation. The polycaprolactone–cellulose acetate fibers obtained by co-axial electrospinning technique and Chitosan–Gelatin scaffolds prepared using freeze-drying techniques were utilized. Initially, the structural properties (fiber size, pore size and porosity) and mechanical properties (elastic modulus and Poisson’s ratio) of scaffolds in phosphate buffered saline at 37 °C were evaluated. The CFD simulations were performed by coupling fluid flow, described by Brinkman equation, with structural mechanics using a moving mesh. The experimentally obtained pressure drop values for both 1 mm thick and 2 mm thick scaffolds agreed with simulation results. To evaluate the effect of permeability and elastic modulus on pressure drop, CFD predictions were extended to a broad range of permeabilities spanning synthetic scaffolds and tissues, elastic moduli, and Poisson’s ratio. Results indicated an increase in pressure drop with increase in permeability. Scaffolds with higher elastic modulus performed better and the effect of Poisson’s ratio was insignificant. Flow induced deformation was negligible in axial-flow bioreactor. In summary, scaffold permeabilities can be calculated using scaffold microarchitecture and can be used in non-invasive monitoring of tissue regeneration.

Keywords

Permeability Fibrous scaffolds Elastic modulus Axial-flow Flow-through Soft tissue Brinkman equation Poroelasticity 

References

  1. 1.
    Azuaje, F. Computational discrete models of tissue growth and regeneration. Brief. Bioinform. 12(1):64–77, 2011.PubMedCrossRefGoogle Scholar
  2. 2.
    Bhaskar, P. R. Design of an Axial Flow Bioreactor for Tissue Engineering. Stillwater, OK: Oklahoma State University, 2012.Google Scholar
  3. 3.
    Chu, X. H., X. L. Shi, Z. Q. Feng, J. Y. Gu, H. Y. Xu, Y. Zhang, Z. Z. Gu, and Y. T. Ding. In vitro evaluation of a multi-layer radial-flow bioreactor based on galactosylated chitosan nanofiber scaffolds. Biomaterials 30(27):4533–4538, 2009.PubMedCrossRefGoogle Scholar
  4. 4.
    Correia, C., S. Bhumiratana, R. A. Sousa, R. L. Reis, and G. Vunjak-Novakovic. Sequential application of steady and pulsatile medium perfusion enhanced the formation of engineered bone. Tissue Eng. Part. A 19(9–10):1244–1254, 2013.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Cowin, S. C. Bone poroelasticity. J. Biomech. 32(3):217–238, 1999.PubMedCrossRefGoogle Scholar
  6. 6.
    de Kloe, J., A. van der Steen, H. Öksüzoğlu, and H. Dijkstra. A fully implicit parallel ocean model using MUMPS. J. Supercomput. 23(2):167–183, 2002.CrossRefGoogle Scholar
  7. 7.
    Devarapalli, M., B. J. Lawrence, and S. V. Madihally. Modeling nutrient consumptions in large flow-through bioreactors for tissue engineering. Biotechnol. Bioeng. 103(5):1003–1015, 2009.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Dias, M. R., P. R. Fernandes, J. M. Guedes, and S. J. Hollister. Permeability analysis of scaffolds for bone tissue engineering. J. Biomech. 45(6):938–944, 2012.PubMedCrossRefGoogle Scholar
  9. 9.
    Dvir, T., N. Benishti, M. Shachar, and S. Cohen. A novel perfusion bioreactor providing a homogenous milieu for tissue regeneration. Tissue Eng. 12(10):2843–2852, 2006.PubMedCrossRefGoogle Scholar
  10. 10.
    Goulet, R. W., S. A. Goldstein, M. J. Ciarelli, J. L. Kuhn, M. B. Brown, and L. A. Feldkamp. The relationship between the structural and orthogonal compressive properties of trabecular bone. J. Biomech. 27(4):375–539, 1994.PubMedCrossRefGoogle Scholar
  11. 11.
    Griffith, L. G., and G. Naughton. Tissue engineering-current challenges and expanding opportunities. Science 295(5557):1009–1014, 2002.PubMedCrossRefGoogle Scholar
  12. 12.
    Hayashi, K. Mechanical properties of soft tissues and arterial walls. In: Biomechanics of Soft Tissue in Cardiovascular Systems, edited by G. Holzapfel and R. W. Ogden. New York: Springer, 2003.Google Scholar
  13. 13.
    Hellmich, C., and F. J. Ulm. Drained and undrained poroelastic properties of healthy and pathological bone: a poro-micromechanical investigation. Transp. Porous Media 58(3):243–268, 2005.CrossRefGoogle Scholar
  14. 14.
    Hidalgo-Bastida, L. A., S. Thirunavukkarasu, S. Griffiths, S. H. Cartmell, and S. Naire. Modeling and design of optimal flow perfusion bioreactors for tissue engineering applications. Biotechnol. Bioeng. 109(4):1095–1099, 2012.PubMedCrossRefGoogle Scholar
  15. 15.
    Hong, J. K., and S. V. Madihally. Next generation of electrosprayed fibers for tissue regeneration. Tissue Eng. Part B 17(2):125–142, 2011.CrossRefGoogle Scholar
  16. 16.
    Iyer, P., K. J. Walker, and S. V. Madihally. Increased matrix synthesis by fibroblasts with decreased proliferation on synthetic chitosan–gelatin porous structures. Biotechnol. Bioeng. 109(5):1314–1325, 2012.PubMedCrossRefGoogle Scholar
  17. 17.
    Jackson, G. W., and D. F. James. The permeability of fibrous porous media. Can. J. Chem. Eng. 64(3):364–374, 1986.CrossRefGoogle Scholar
  18. 18.
    Jacob, B. Dynamics of Fluid in Porous Media. New York: American Elsevier Publishing Company Inc., 1988.Google Scholar
  19. 19.
    Jones, A. C., C. H. Arns, A. P. Sheppard, D. W. Hutmacher, B. K. Milthorpe, and M. A. Knackstedt. Assessment of bone ingrowth into porous biomaterials using MICRO-CT. Biomaterials 28(15):2491–2504, 2007.PubMedCrossRefGoogle Scholar
  20. 20.
    Khayyeri, H., S. Checa, M. Tagil, F. J. O’Brien, and P. J. Prendergast. Tissue differentiation in an in vivo bioreactor: in silico investigations of scaffold stiffness. J. Mater. Sci. Mater. Med. 21(8):2331–2336, 2010.PubMedCrossRefGoogle Scholar
  21. 21.
    Koponen, A., D. Kandhai, E. Hellen, M. Alava, A. Hoekstra, M. Kataja, K. Niskanen, P. Sloot, and J. Timonen. Permeability of three-dimensional random fiber webs. Phys. Rev. Lett. 80(4):716–719, 1998.CrossRefGoogle Scholar
  22. 22.
    Koponen, A., M. Kataja, and J. Timonen. Permeability and effective porosity of porous media. Phys. Rev. E 56(3):3319–3325, 1997.CrossRefGoogle Scholar
  23. 23.
    Lawrence, B. J., M. Devarapalli, and S. V. Madihally. Flow dynamics in bioreactors containing tissue engineering scaffolds. Biotechnol. Bioeng. 102(3):935–947, 2009.PubMedCrossRefGoogle Scholar
  24. 24.
    Lawrence, B. J., E. L. Maase, H. K. Lin, and S. V. Madihally. Multilayer composite scaffolds with mechanical properties similar to small intestinal submucosa. J. Biomed. Mater. Res. A 88(3):634–643, 2009.PubMedGoogle Scholar
  25. 25.
    Lawrence, B. J., and S. V. Madihally. Cell colonization in degradable 3D porous matrices. Cell Adhes. Migr. 2(1):9–16, 2008.CrossRefGoogle Scholar
  26. 26.
    Leclerc, E., Y. Sakai, and T. Fujii. Microfluidic PDMS (Polydimethylsiloxane) bioreactor for large-scale culture of hepatocytes. Biotechnol. Prog. 20(3):750–755, 2004.PubMedCrossRefGoogle Scholar
  27. 27.
    Patrachari, A. R., J. T. Podichetty, and S. V. Madihally. Application of computational fluid dynamics in tissue engineering. J. Biosci. Bioeng. 114(2):123–132, 2012.PubMedCrossRefGoogle Scholar
  28. 28.
    Pennella, F., G. Cerino, D. Massai, D. Gallo, G. Falvo D’Urso Labate, A. Schiavi, M. A. Deriu, A. Audenino, and U. Morbiducci. A survey of methods for the evaluation of tissue engineering scaffold permeability. Ann. Biomed. Eng. 41(10):2027–2041, 2013.PubMedCrossRefGoogle Scholar
  29. 29.
    Podichetty, J. T., D. V. Dhane, and S. V. Madihally. Dynamics of diffusivity and pressure drop in flow-through and parallel-flow bioreactors during tissue regeneration. Biotechnol. Prog. 28(4):1045–1054, 2012.PubMedCrossRefGoogle Scholar
  30. 30.
    Podichetty, J. T., and S. V. Madihally. Modeling of porous scaffold deformation induced by medium perfusion. J. Biomed. Mater. Res. Part B. 2013. doi:10.1002/jbm.b.33054.
  31. 31.
    Pok, S., D. V. Dhane, and S. V. Madihally. Computational simulation modelling of bioreactor configurations for regenerating human bladder. Comput. Methods Biomech. Biomed. Eng. 16(8):840–851, 2013.CrossRefGoogle Scholar
  32. 32.
    Pörtner, R., S. Nagel-Heyer, C. Goepfert, P. Adamietz, and N. M. Meenen. Bioreactor design for tissue engineering. J. Biosci. Bioeng. 100(3):235–245, 2005.PubMedCrossRefGoogle Scholar
  33. 33.
    Pu, F., N. P. Rhodes, Y. Bayon, R. Chen, G. Brans, R. Benne, and J. A. Hunt. The use of flow perfusion culture and subcutaneous implantation with fibroblast-seeded PLLA-collagen 3D scaffolds for abdominal wall repair. Biomaterials 31(15):4330–4340, 2010.PubMedCrossRefGoogle Scholar
  34. 34.
    Ratakonda, S., U. M. Sridhar, R. R. Rhinehart, and S. V. Madihally. Assessing viscoelastic properties of chitosan scaffolds and validation with cyclical tests. Acta Biomater. 8(4):1566–1575, 2012.PubMedCrossRefGoogle Scholar
  35. 35.
    Saad, Y., and M. H. Schultz. GMRES: a generalized minimal residual algorithm for solving nonsymmetric linear systems. SIAM J. Sci. Stat. Comput. 7(3):856–869, 1986.CrossRefGoogle Scholar
  36. 36.
    Sengers, B. G., C. W. Oomens, and F. P. Baaijens. An integrated finite-element approach to mechanics, transport and biosynthesis in tissue engineering. J. Biomech. Eng. 126(1):82–91, 2004.PubMedCrossRefGoogle Scholar
  37. 37.
    Sethuraman, V., K. Makornkaewkeyoon, A. Khalf, and S. V. Madihally. Influence of scaffold forming techniques on stress relaxation behavior of polycaprolactone scaffolds. J. Appl. Polym. Sci. 130(6):4237–4244, 2013.Google Scholar
  38. 38.
    Shimko, D. A., V. F. Shimko, E. A. Sander, K. F. Dickson, and E. A. Nauman. Effect of porosity on the fluid flow characteristics and mechanical properties of tantalum scaffolds. J. Biomed. Mater. Res. Part B 73(2):315–324, 2005.CrossRefGoogle Scholar
  39. 39.
    Strain, A. J., and J. M. Neuberger. A bioartificial liver-state of the art. Science 295(5557):1005–1009, 2002.PubMedCrossRefGoogle Scholar
  40. 40.
    Swartz, M. A., and M. E. Fleury. Interstitial flow and its effects in soft tissues. Annu. Rev. Biomed. Eng. 9:229–256, 2007.PubMedCrossRefGoogle Scholar
  41. 41.
    Whitaker, S. The Forchheimer equation: a theoretical development. Transp. Porous Media 25(1):27–61, 1996.CrossRefGoogle Scholar
  42. 42.
    Zhao, F., and T. Ma. Perfusion bioreactor system for human mesenchymal stem cell tissue engineering: dynamic cell seeding and construct development. Biotechnol. Bioeng. 91(4):482–493, 2005.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhu, X., W. Cui, X. Li, and Y. Jin. Electrospun fibrous mats with high porosity as potential scaffolds for skin tissue engineering. Biomacromolecules 9(7):1795–1801, 2008.PubMedCrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Jagdeep T. Podichetty
    • 1
  • Prasana R. Bhaskar
    • 1
  • Abdurizzagh Khalf
    • 1
  • Sundararajan V. Madihally
    • 1
  1. 1.School of Chemical EngineeringOklahoma State UniversityStillwaterUSA

Personalised recommendations