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01-09-2012 | Original Article

Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering

Authors: Davod Mohebbi-Kalhori, Amin Behzadmehr, Charles J. Doillon, Afra Hadjizadeh

Published in: Journal of Artificial Organs | Issue 3/2012

Abstract

The use of hollow-fiber membrane bioreactors (HFMBs) has been proposed for three-dimensional bone tissue growth at the clinical scale. However, to achieve an efficient HFMB design, the relationship between cell growth and environmental conditions must be determined. Therefore, in this work, a dynamic double-porous media model was developed to determine nutrient-dependent cell growth for bone tissue formation in a HFMB. The whole hollow-fiber scaffold within the bioreactor was treated as a porous domain in this model. The domain consisted of two interpenetrating porous regions, including a porous lumen region available for fluid flow and a porous extracapillary space filled with a collagen gel that contained adherent cells for promoting long-term growth into tissue-like mass. The governing equations were solved numerically and the model was validated using previously published experimental results. The contributions of several bioreactor design and process parameters to the performance of the bioreactor were studied. The results demonstrated that the process and design parameters of the HFMB significantly affect nutrient transport and thus cell behavior over a long period of culture. The approach presented here can be applied to any cell type and used to develop tissue engineering hollow-fiber scaffolds.

Hadjizadeh A, Mohebbi-Kalhori D. Porous hollow membrane sheet for tissue engineering applications. J Biomed Mater Res A. 2010;93:1140–50.PubMed

Mohebbi-Kalhori D. A positron emission tomography approach to visualize flow perfusion in hollow-fiber membrane bioreactors. J Artif Organs. 2011;14:318–30.PubMedCrossRef

Abdullah NS, Das DB, Ye H, Cui ZF. 3D bone tissue growth in hollow fibre membrane bioreactor: implications of various process parameters on tissue nutrition. Int J Artif Organs. 2006;29:841–51.PubMed

Liu G, Zhao L, Cui L, Liu W, Cao Y. Tissue-engineered bone formation using human bone marrow stromal cells and novel beta-tricalcium phosphate. Biomed Mater (Bristol, England). 2007;2:78–86.

Meinel L, Karageorgiou V, Fajardo R, Snyder B, Shinde-Patil V, Zichner L, Kaplan D, Langer R, Vunjak-Novakovic G. Bone tissue engineering using human mesenchymal stem cells: effects of scaffold material and medium flow. Ann Biomed Eng. 2004;32:112–22.PubMedCrossRef

Ogawa M. Differentiation and proliferation of hematopoietic stem cells. Blood. 1993;81:2844–53.PubMed

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.PubMedCrossRef

Ho AD, Wagner W, Franke W. Heterogeneity of mesenchymal stromal cell preparations. Cytotherapy. 2008;10:320–30.PubMedCrossRef

Chien HH, Lin WL, Cho MI. Down-regulation of osteoblastic cell differentiation by epidermal growth factor receptor. Calcif Tissue Int. 2000;67:141–50.PubMedCrossRef

10.

Zhao F, Pathi P, Grayson W, Xing Q, Locke BR, Ma T. Effects of oxygen transport on 3-D human mesenchymal stem cell metabolic activity in perfusion and static cultures: experiments and mathematical model. Biotechnol Prog. 2005;21:1269–80.PubMedCrossRef

11.

Vunjak-Novakovic G, Meinel L, Altman G, Kaplan D. Bioreactor cultivation of osteochondral grafts. Orthod Craniofac Res. 2005;8:209–18.PubMedCrossRef

12.

Ellis MJ, Chaudhuri JB. Poly(lactic-co-glycolic acid) hollow fibre membranes for use as a tissue engineering scaffold. Biotechnol Bioeng. 2007;96:177–87.PubMedCrossRef

13.

Dunn JCY, Chan WY, Cristini V, Kim JS, Lowengrub J, Singh S, Wu BM. Analysis of cell growth in three-dimensional scaffolds. Tissue Eng. 2006;12:705–16.PubMedCrossRef

14.

Bettahalli NM, Vicente J, Moroni L, Higuera GA, van Blitterswijk CA, Wessling M, Stamatialis DF. Integration of hollow fiber membranes improves nutrient supply in three-dimensional tissue constructs. Acta Biomater. 2011;7:3312–24.PubMedCrossRef

15.

Cartmell SH, Porter BD, Garcia AJ, Guldberg RE. Effect of medium perfusion rate on cell-seeded three-dimensional bone construct in vitro. Tissue Eng. 2003;9:1197–203.PubMedCrossRef

16.

Kellner K, Liebsch G, Klimant I, Wolfbeis OS, Blunk T, Schulz MB, Gopferich A. Determination of oxygen gradients in engineered tissue using a fluorescent sensor. Biotechnol Bioeng. 2002;80:73–83.PubMedCrossRef

17.

Abdullah NS, Das DB. Modelling nutrient transport in hollow fibre membrane bioreactor for growing bone tissue with consideration of multi-component interactions. Chem Eng Sci. 2007;62:5821–39.CrossRef

18.

Pierre J, Oddou C. Engineered bone culture in a perfusion bioreactor: a 2D computational study of stationary mass and momentum transport. Comput Methods Biomech Biomed Eng. 2007;10:429–38.CrossRef

19.

Chesnick IE, Avallone FA, Leapman RD, Landis WJ, Eidelman N, Potter K. Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and FTIR microspectroscopy. Bone. 2007;40:904–12.PubMedCrossRef

20.

Ye H, Xia Z, Ferguson DJ, Triffitt JT, Cui Z. Studies on the use of hollow fibre membrane bioreactors for tissue generation by using rat bone marrow fibroblastic cells and a composite scaffold. J Mater Sci Mater Med. 2007;18:641–8.PubMedCrossRef

21.

Das DB. Multiscale simulation of nutrient transport in hollow fibre membrane bioreactor for growing bone tissue: sub-cellular scale and beyond. Chem Eng Sci. 2007;62:3627–39.CrossRef

22.

Sikavitsas VI, Bancroft GN, Mikos AG. Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor. J Biomed Mater Res. 2002;62:136–48.PubMedCrossRef

23.

Zhang N, Heather LN, Shila T, Wen X. Fabrication of nanocrystalline hydroxyapatite doped degradable composite hollow fiber for guided and biomimetic bone tissue engineering. Mater Sci Eng. 2007;27:599–606.CrossRef

24.

Ye H, Das DB, Triffitt JT, Cui Z. Modelling nutrient transport in hollow fibre membrane bioreactors for growing three-dimensional bone tissue. J Membr Sci. 2006;272:169–78.CrossRef

25.

Krogh A. The rate of diffusion of gases through animal tissues, with some remarks on the coefficient of invasion. J Physiol. 1919;52:391–408.PubMed

26.

Labecki M, Piret JM, Bowen BD. Effect of free convection on three-dimensional protein transport in hollow-fiber bioreactors. AIChE J. 2004;50:1974–90.CrossRef

27.

Ding W, He L, Zhao G, Zhang H, Shu Z, Gao D. Double porous media model for mass transfer of hemodialyzers. Int J Heat Mass Transf. 2004;47:4849–55.CrossRef

28.

Chresand TJ, Gillies RJ, Dale BE. Optimum fiber spacing in a hollow fiber bioreactor. Biotechnol Bioeng. 1988;32:983–92.PubMedCrossRef

29.

Sengers BG, Taylor M, Please CP, Oreffo RO. Computational modeling of cell spreading and tissue regeneration in porous scaffolds. Biomaterials. 2007;28:1926–40.PubMedCrossRef

30.

Galban CJ, Locke BR. Analysis of cell growth kinetics and substrate diffusion in a polymer scaffold. Biotechnol Bioeng. 1999;65:121–32.PubMedCrossRef

31.

Mehta K, Linderman JJ. Model-based analysis and design of a microchannel reactor for tissue engineering. Biotechnol Bioeng. 2006;94:596–609.PubMedCrossRef

32.

Brotherton JD, Chau PC. Modeling of axial-flow hollow fiber cell culture bioreactors. Biotechnol Prog. 1996;12:575–90.CrossRef

33.

McClelland RE, MacDonald JM, Coger RN. Modeling O₂ transport within engineered hepatic devices. Biotechnol Bioeng. 2003;82:12–27.PubMedCrossRef

34.

Zhang Q, Cussler EL. Microporous hollow fibre for gas absorption. Part II. Mass transfer across the membrane. J Membr Sci. 1985;23:332–45.

35.

Boyd RF, Lopez M, Stephens CL, Velez GM, Ramirez CA, Zydney AL. Solute washout experiments for characterizing mass transport in hollow fiber immunoisolation membranes. Ann Biomed Eng. 1998;26:618–26.PubMedCrossRef

36.

Mota M, Yelshin A, Fidaleo M, Flickinger MC. Modelling diffusivity in porous polymeric membranes with an intermediate layer containing microbial cells. Biochem Eng J. 2007;37:285–93.CrossRef

37.

Chresand TJ, Dale BE, Hanson SL, Gillies RJ. A stirred bath technique for diffusivity measurement in cell matrices. Biotechnol Bioeng. 1988;32:1029–36.PubMedCrossRef

38.

Maxwell JC. A treatise on electricity and magnetism. New York: Clarendon Press; 1973.

39.

Brown DA, MacLellan WR, Laks H, Dunn JC, Wu BM, Beygui RE. Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue. Biotechnol Bioeng. 2007;97:962–75.PubMedCrossRef

40.

Westrin BA, Axelsson A. Diffusion in gels containing immobilized cells: a critical review. Biotechnol Bioeng. 1991;38:439–46.PubMedCrossRef

41.

Curcio S, Calabro V, Iorio G. A theoretical and experimental analysis of a membrane bioreactor performance in recycle configuration. J Membr Sci. 2006;273:129–42.CrossRef

42.

Chow DC, Wenning LA, Miller WM, Papoutsakis ET. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh’s model. Biophys J. 2001;81:675–84.PubMedCrossRef

43.

Pathi P, Ma T, Locke BR. Role of nutrient supply on cell growth in bioreactor design for tissue engineering of hematopoietic cells. Biotechnol Bioeng. 2005;89:743–58.PubMedCrossRef

44.

Janssen FW, Oostra J, Oorschot A, van Blitterswijk CA. A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept. Biomaterials. 2006;27:315–23.PubMedCrossRef

45.

Tjia JS, Moghe PV. Regulation of cell motility on polymer substrates via “dynamic,” cell internalizable, ligand microinterfaces. Tissue Eng. 2002;8:247–61.PubMedCrossRef

46.

Cho CH, Park J, Nagrath D, Tilles AW, Berthiaume F, Toner M, Yarmush ML. Oxygen uptake rates and liver-specific functions of hepatocyte and 3T3 fibroblast co-cultures. Biotechnol Bioeng. 2007;97:188–99.PubMedCrossRef

47.

Windhaber RA, Wilkins RJ, Meredith D. Functional characterisation of glucose transport in bovine articular chondrocytes. Pflugers Arch Eur J Phys. 2003;446:572–7.CrossRef

48.

Obradovic B, Carrier RL, Vunjak-Novakovic G, Freed LE. Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage. Biotechnol Bioeng. 1999;63:197–205.PubMedCrossRef

49.

Kleinstreuer C, Agarwal SS. Analysis and simulation of hollow-fiber bioreactor dynamics. Biotechnol Bioeng. 1986;28:1233–40.PubMedCrossRef

50.

Ramanujan S, Pluen A, McKee TD, Brown EB, Boucher Y, Jain RK. Diffusion and convection in collagen gels: implications for transport in the tumor interstitium. Biophys J. 2002;83:1650–60.PubMedCrossRef

51.

Korin N, Bransky A, Dinnar U, Levenberg S. A parametric study of human fibroblasts culture in a microchannel bioreactor. Lab Chip. 2007;7:611–7.PubMedCrossRef

52.

Sun S, Cho M. Human fibroblast migration in three-dimensional collagen gel in response to noninvasive electrical stimulus. II. Identification of electrocoupling molecular mechanisms. Tissue Eng. 2004;10:1558–65.PubMed

53.

Burrows RC, Freeman D, Charlop AW, Wiseman W, Adamsen TCH, Krohn A, Spence AM. [18F]-2-fluoro-2-deoxyglucose transport kinetics as a function of extracellular glucose concentration in malignant glioma, fibroblast and macrophage cells in vitro. Nucl Med Biol. 2004;31:1–9.PubMedCrossRef

Title: Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering
Authors: Davod Mohebbi-Kalhori
Amin Behzadmehr
Charles J. Doillon
Afra Hadjizadeh
Publication date: 01-09-2012
Publisher: Springer Japan
Published in: Journal of Artificial Organs / Issue 3/2012
Print ISSN: 1434-7229
Electronic ISSN: 1619-0904
DOI: https://doi.org/10.1007/s10047-012-0649-1

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Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering

Abstract

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Abstract

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