全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
Processes  2014 

Model-Based Optimization of Scaffold Geometry and Operating Conditions of Radial Flow Packed-Bed Bioreactors for Therapeutic Applications

DOI: 10.3390/pr2010034

Keywords: bioreactor, model, oxygen, radial flow, tissue engineering, transport

Full-Text   Cite this paper   Add to My Lib

Abstract:

Radial flow perfusion of cell-seeded hollow cylindrical porous scaffolds may overcome the transport limitations of pure diffusion and direct axial perfusion in the realization of bioengineered substitutes of failing or missing tissues. Little has been reported on the optimization criteria of such bioreactors. A steady-state model was developed, combining convective and dispersive transport of dissolved oxygen with Michaelis-Menten cellular consumption kinetics. Dimensional analysis was used to combine more effectively geometric and operational variables in the dimensionless groups determining bioreactor performance. The effectiveness of cell oxygenation was expressed in terms of non-hypoxic fractional construct volume. The model permits the optimization of the geometry of hollow cylindrical constructs, and direction and magnitude of perfusion flow, to ensure cell oxygenation and culture at controlled oxygen concentration profiles. This may help engineer tissues suitable for therapeutic and drug screening purposes.

References

[1]  Langer, R.; Vacanti, J.P.; Vacanti, C.A.; Atala, A.; Freed, L.E.; Vunjak-Novakovic, G. Tissue engineering: Biomedical applications. Tissue Eng. 1995, 1, 151–161, doi:10.1089/ten.1995.1.151.
[2]  VandeVord, P.J.; Nasser, S.; Wooley, P.H. Immunological responses to bone soluble proteins in recipients of bone allografts. J. Orthop. Res. 2005, 23, 1059–1064, doi:10.1016/j.orthres.2004.12.004.
[3]  Zeilinger, K.; Holland, G.; Sauer, I.M.; Efimova, E.; Kardassis, D.; Obermayer, N.; Liu, M.; Neuhaus, P.; Gerlach, J.C. Time course of primary liver cell reorganization in three-dimensional high-density bioreactors for extracorporeal liver support: An immunohistochemical and ultrastructural study. Tissue Eng. 2004, 10, 1113–1124.
[4]  Rotem, A.; Toner, M.; Bhatia, S.N.; Foy, B.D.; Tomkins, R.G.; Yarmush, M.L. Oxygen is a factor determining in vitro tissue assembly: Effects on attachment and spreading of hepatocytes. Biotechnol. Bioeng. 1994, 43, 654–660, doi:10.1002/bit.260430715.
[5]  Catapano, G.; de Bartolo, L.; Lombardi, C.P.; Drioli, E. The effect of oxygen transport resistances on the viability and functions of isolated rat hepatocytes. Int. J. Artif. Organs 1996, 19, 31–41.
[6]  Allen, J.W.; Khetani, S.R.; Bhatia, S.N. In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol. Sci. 2005, 84, 110–119, doi:10.1093/toxsci/kfi052.
[7]  Volkmer, E.; Drosse, I.; Otto, S.; Stangellmayer, A.; Stengele, M.; Kallukalam, B.C.; Mutschler, W.; Schieker, M. Hypoxia in static and dynamic 3D culture systems for tissue engineering of bone. Tissue Eng. Part A 2008, 14, 1331–1340, doi:10.1089/ten.tea.2007.0231.
[8]  Griffith, C.K.; George, S.C. The effect of hypoxia on in vitro prevascularization of a thick soft tissue. Tissue Eng. Part A 2009, 15, 2423–2434, doi:10.1089/ten.tea.2008.0267.
[9]  Catapano, G. Mass transfer limitations to the performance of membrane bioartificial liver support devices. Int. J. Artif. Organs 1996, 19, 51–68.
[10]  Wendt, D.; Marsano, A.; Jakob, M.; Heberer, M.; Martin, I. Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity. Biotechnol. Bioeng. 2003, 84, 205–214, doi:10.1002/bit.10759.
[11]  Glicklis, R.; Shapiro, L.; Agbaria, R.; Merchuk, J.C.; Cohen, S. Hepatocyte behavior within three-dimensional porous alginate scaffolds. Biotechnol. Bioeng. 2000, 67, 344–353, doi:10.1002/(SICI)1097-0290(20000205)67:3<344::AID-BIT11>3.0.CO;2-2.
[12]  Gaspar, D.A.; Gomide, V.; Monteiro, F.J. The role of perfusion bioreactors in bone tissue engineering. Biomatter 2012, 2, 1–9, doi:10.4161/biom.19429.
[13]  Muschler, G.F.; Nakamoto, C.; Griffith, L. Engineering principles of clinical cell-based tissue engineering. J. Bone Joint Surg. 2004, 86, 1541–1558.
[14]  Griffith, C.K.; George, S.C. Diffusion limits of an in vitro thick prevascularized tissue. Tissue Eng. 2005, 11, 257–266, doi:10.1089/ten.2005.11.257.
[15]  Jaesung, P.; Yawen, L.; Berthiaume, F.; Toner, M.; Yarmush, M.L.; Tilles, A.W. Radial flow hepatocyte bioreactor using stacked microfabricated grooved substrates. Biotechnol. Bioeng. 2008, 99, 455–467, doi:10.1002/bit.21572.
[16]  Niu, M.; Hammond, P.; Coger, R.N. The effectiveness of a novel cartridge-based bioreactor design in supporting liver cells. Tissue Eng. Part A 2009, 15, 2903–2916, doi:10.1089/ten.tea.2008.0279.
[17]  Granet, C.; Laroche, N.; Vico, L.; Alexandre, C.; Lafage-Proust, M.H. Rotating wall vessel, promising bioreactors for osteoblastic cell culture: Comparison with other 3D conditions. Med. Biol. Eng. Comput. 1998, 36, 513–519, doi:10.1007/BF02523224.
[18]  Sikavitsas, V.I.; Bancroft, G.N.; Mikos, A.G. 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, 36–48.
[19]  Catapano, G.; Gerlach, J.C. Bioreactors for liver tissue engineering. On-line encyclopedia of tissue engineering. Topics in Tissue Engineering; Biomaterials and Tissue Engineering Group: Oulu, Finland, 2007; Volume 3. Chaper 8, pp. 1–42. Available online: http://www.oulu.fi/spareparts/ebook_topics_in_t_e_vol3/ (accessed on 27 December 2013).
[20]  Radisic, M.; Deen, W.; Langer, R.; Vunjak-Novakovic, G. Mathematical model of oxygen distribution in engineered cardic tissue with parallel channel array perfused with culture medium containing oxygen carriers. Am. J. Physiol. Heart Circ. Physiol. 2005, 288, H1278–H1289.
[21]  Sullivan, J.P.; Palmer, A.F. Targeted oxygen delivery within hepatic hollow fiber bioreactors via supplementation of hemoglobin-based oxygen carriers. Biotechnol. Prog. 2006, 22, 1374–1387.
[22]  McClelland, R.E.; Coger, R.N. Use of micropathways to improve oxygen transport in a hepatic system. Trans. ASME 2000, 122, 268–273.
[23]  McClelland, R.E.; Coger, R.N. Effects of enhanced O2 transport on hepatocytes packed within a bioartificial liver device. Tissue Eng. 2004, 10, 253–266, doi:10.1089/107632704322791899.
[24]  Kim, S.S.; Sundback, C.A.; Kaihara, S.; Benvenuto, M.S.; Kim, B.-S.; Mooney, D.J.; Vacanti, J.P. Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system. Tissue Eng. 2000, 6, 39–44, doi:10.1089/107632700320874.
[25]  Bancroft, G.N.; Sikavitsas, V.I.; van der Dolder, J.; Sheffield, T.L.; Ambrose, C.G.; Jansen, J.A.; Mikos, A.G. Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc. Natl. Acad. Sci. USA 2002, 99, 12600–12605, doi:10.1073/pnas.202296599.
[26]  Warnock, J.N.; Bratch, K.; Al-Rubeai, M. Packed-bed bioreactors. In Bioreactors for Tissue Engineering, 1st ed.; Chauduri, J., Al-Rubeai, M., Eds.; Springer Verlag: Dordrecht, The Netherlands, 2005; pp. 87–114.
[27]  Fr?hlich, M.; Grayson, W.L.; Marolt, D.; Gimble, J.M.; Kregar-Velikonja, N.; Vunjak-Novakovic, G. Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng. 2010, 16, 179–189.
[28]  Piret, J.M.; Devens, D.A.; Cooney, C.L. Nutrient and metabolite gradients in mammalian-cell hollow fiber bioreactors. Can. J. Chem. Eng. 1991, 69, 421–428, doi:10.1002/cjce.5450690204.
[29]  Fassnacht, D.; P?rtner, R. Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed-bed reactors. J. Biotechnol. 1999, 72, 169–184, doi:10.1016/S0168-1656(99)00129-7.
[30]  Singh, H.; Ang, E.S.; Lim, T.T.; Hutmacher, D.W. Flow modeling in a novel non-perfusion conical bioreactor. Biotechnol. Bioeng. 2007, 97, 1291–1299, doi:10.1002/bit.21327.
[31]  Kurosawa, H.; Markl, H.; Niebhur-Redder, C.; Matsamura, M. Dialysis bioreactor with radial flow fixed bed for animal cell culture. J. Ferment. Bioeng. 1991, 72, 41–45.
[32]  Kino-Oka, M.; Taya, M. Design and operation of a radial flow bioreactor for reconstruction of cultured tissues. In Bioreactors for Tissue Engineering, 1st ed.; Chauduri, J., Al-Rubeai, M., Eds.; Springer Verlag: Dordrecht, The Netherlands, 2005; pp. 115–133.
[33]  Guillouzo, A.; Guguen-Guillouzo, C. Evolving concepts in liver tissue modeling and implications for in vitro toxicology. Expert Opin. Drug Metab. Toxicol. 2008, 4, 1279–1294, doi:10.1517/17425255.4.10.1279.
[34]  Kitagawa, T.; Yamaoka, T.; Iwase, R.; Murakami, A. Three-dimensional cell seeding and growth in radial-flow perfusion bioreactor for in vitro tissue reconstruction. Biotechnol. Bioeng. 2006, 93, 947–954, doi:10.1002/bit.20797.
[35]  Xie, Y.; Hardouin, P.; Zhu, Z.; Tang, T.; Dai, K.; Lu, J. Three-dimensional flow perfusion culture system for stem cell proliferation inside the critical-size β-tricalcium phosphate scaffold. Tissue Eng. 2006, 12, 3535–3543, doi:10.1089/ten.2006.12.3535.
[36]  Olivier, V.; Hivart, P.; Descamps, M.; Hardouin, P. In vitro culture of large bone substitutes in a new bioreactor: Importance of the flow direction. Biomed. Mater. 2007, 2, 174–180, doi:10.1088/1748-6041/2/3/002.
[37]  Kawada, M.; Nagamori, S.; Aizaki, H.; Fukaya, K.; Niiya, M.; Matsuura, T.; Sujino, H.; Hasumura, S.; Yashida, H.; Mizutani, S.; et al. Massive culture of human liver cancer cells in a newly developed radial flow bioreactor system: Ultrafine structure of functionally enhanced hepatocarcinoma cell lines. In Vitro Cell Dev. Biol. Anim. 1998, 34, 109–115, doi:10.1007/s11626-998-0092-z.
[38]  Hongo, T.; Kajikawa, M.; Ishida, S.; Ozawa, S.; Ohno, Y.; Sawada, J.; Umezawa, A.; Ishikawa, Y.; Kobayashi, T.; Honda, H. Three-dimensional high-density culture of HepG2 cells in a 5-mL radial flow bioreactor for construction of artificial liver. J. Biosci. Bioeng. 2005, 99, 237–244, doi:10.1263/jbb.99.237.
[39]  Miskon, A.; Sasaki, N.; Yamaoka, T.; Uyama, H.; Kodama, M. Radial flow type bioreactor for bioartificial liver assist using PTFE non-woven fabric coated with poly-amino acid urethane copolymer. Macromol. Symp. 2007, 249-250, 151–158, doi:10.1002/masy.200750325.
[40]  Morsiani, E.; Galavotti, D.; Puviani, A.C.; Valieri, L.; Brogli, M.; Tosatti, S.; Pazzi, P.; Azzena, G. Radial flow bioreactor outperforms hollow-fiber modulus as a perfusing culture system for primary porcine hepatocytes. Transplant. Proc. 2000, 32, 2715–2718, doi:10.1016/S0041-1345(00)01853-4.
[41]  Morsiani, E.; Brogli, M.; Galavotti, D.; Bellini, T.; Ricci, D.; Pazzi, P.; Puviani, A.C. Long-term expression of highly differentiated functions by isolated porcine hepatocytes perfused in a radial-flow bioreactor. Artif. Organs 2001, 25, 740–748, doi:10.1046/j.1525-1594.2001.06669.x.
[42]  Saito, M.; Matsuura, T.; Masaki, T.; Maehashi, H.; Shimizu, K.; Hataba, Y.; Iwahori, T.; Suzuki, T.; Braet, F. Reconstruction of liver organoid using bioreactor. World J. Gastroenterol. 2006, 12, 1881–1888.
[43]  Ishii, Y.; Saito, R.; Marushima, H.; Ito, R.; Sakamoto, T.; Yanaga, K. Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor. World J. Gastroenterol. 2008, 14, 2740–2747, doi:10.3748/wjg.14.2740.
[44]  Tharakan, J.P.; Chau, P.C. Modeling and analysis of radial flow mammalian cell culture. Biotechnol. Bioeng. 1987, 29, 657–671, doi:10.1002/bit.260290602.
[45]  Cima, L.G.; Blanch, H.W.; Wilke, C.R. A theoretical and experimental evaluation of a novel radial-flow hollow fiber reactor for mammalian cell culture. Bioprocess Eng. 1990, 5, 19–30, doi:10.1007/BF00369643.
[46]  B?hmann, A.; P?rtner, R.; Schmieding, J.; Kasche, V.; Markl, H. The membrane dialysis bioreactor with integrated radial-flow fixed bed—A new approach for continuous cultivation of animal cells. Cytotechnology 1992, 9, 51–57, doi:10.1007/BF02521731.
[47]  P?rtner, R.; Platas, O.B.; Fassnacht, D.; Nehring, D.; Czermak, P.; Markl, H. Fixed bed reactors for the cultivation of mammalian cells: Design, performance and scale-up. Open Biotechnol. J. 2007, 1, 41–46.
[48]  Chang, H.C.; Saucier, M.; Calo, J.M. Design criterion for radial flow fixed-bed reactors. AIChE J. 1983, 29, 1039–1041, doi:10.1002/aic.690290624.
[49]  Delgado, J. A critical review of dispersion in packed beds. Heat Mass Transfer 2006, 42, 279–310, doi:10.1007/s00231-005-0019-0.
[50]  Fogler, H.S. Elements of Chemical Reaction Engineering, 4th ed. ed.; Prentice Hall: Westford, MA, USA, 2006; pp. 946–943.
[51]  Bird, R.B.; Stewart, W.E.; Lightfoot, E.N. Transport Phenomena, 2nd ed. ed.; John Wiley & Sons, Inc.: New York, NY, USA, 2007; pp. 545–568.
[52]  Han, P.; Bartels, D.M. Temperature dependence of oxygen diffusion in H2O and D2O. J. Phys. Chem. 1996, 100, 5597–5602, doi:10.1021/jp952903y.
[53]  Abdullah, N.S.; Das, D.B.; Ye, H.; Cui, Z.F. 3-D bone tissue growth in hollow fibre membrane bioreactor: Implications of various process parameters on tissue nutrition. Int. J. Artif. Organs 2006, 29, 841–851.
[54]  Zahm, A.M.; Bucaro, M.A.; Ayyaswamy, P.S.; Srinivas, V.; Shapiro, I.M.; Adams, C.S.; Mukundakrishnan, K. Numerical modeling of oxygen distribution in cortical and cancellous bone: Oxygen availability governs osteonal and trabecular dimensions. Am. J. Physiol. Cell Physiol. 2010, 229, C922–C929.
[55]  Chen, G.; Palmer, A.F. Hemoglobin-based oxygen carrier and convection enhanced oxygen transport in a hollow fiber bioreactor. Biotechnol. Bioeng. 2009, 102, 1603–1612, doi:10.1002/bit.22200.
[56]  Loiacono, L.A.; Shapiro, D.S. Detection of hypoxia at the cellular level. Crit. Care Clin. 2010, 26, 409–421, doi:10.1016/j.ccc.2009.12.001.
[57]  Clarke, B. Normal bone anatomy. Clin. J. Am. Soc. Nephrol. 2008, 3, S131–S139, doi:10.2215/CJN.04151206.
[58]  Tortora, G.J.; Derrickson, B. Principles of Anatomy and Physiology, 11th ed. ed.; John Wiley & Sons, Inc.: New York, NY, USA, 2006.
[59]  Ponzi, P.R.; Kaye, L.A. Effect of flow maldistribution on conversion and selectivity in radial flow fixed-bed reactors. AIChE J. 1979, 25, 100–108, doi:10.1002/aic.690250111.
[60]  Komarova, S.V.; Ataullakhanov, F.I.; Globus, R.K. Bioenergetics and mitochondrial transmembrane potential during differentiation of cultured osteoblasts. Am. J. Physiol. Cell Physiol. 2000, 279, C1220–C1229.
[61]  Balis, U.J.; Behnia, K.; Dwarakanath, B.; Bhatia, S.N.; Sullivan, S.J.; Yarmush, M.L.; Toner, M. Oxygen consumption characteristics of porcine hepatocytes. Metab. Eng. 1999, 1, 49–62, doi:10.1006/mben.1998.0105.
[62]  Mehta, K.; Mehta, G.; Takayama, S.; Linderman, J. Quantitative inference of cellular parameters from microfluidic cell culture systems. Biotechnol. Bioeng. 2009, 103, 966–974, doi:10.1002/bit.22334.
[63]  Wang, S.; Tarbell, J.M. Effect of fluid flow on smooth muscle in a 3-dimensional collagen gel model. Arterioscler. Thromb. Vasc. Biol. 2000, 20, 2220–2225, doi:10.1161/01.ATV.20.10.2220.
[64]  Christi, Y. Hydrodynamic damage to animal cells. Crit. Rev. Biotechnol. 2001, 21, 67–110, doi:10.1080/20013891081692.
[65]  Navdeep, S.; Chandel, G.R.; Budinger, S. The cellular basis for diverse responses to oxygen. Free Radic. Biol. Med. 2007, 42, 165–174, doi:10.1016/j.freeradbiomed.2006.10.048.
[66]  Moustafa, T.; Badr, S.; Hassan, M.; Abba, I.A. Effect of flow direction on the behavior of radial flow catalytic reactors. Asia-Pac. J. Chem. Eng. 2012, 7, 307–316, doi:10.1002/apj.509.
[67]  Rowley, J.A.; Timmins, M.; Galbraith, W.; Garvin, J.; Kosovsky, M.; Heidaran, M. Oxygen consumption as a predictor of growth and differentiation of MC3T3-E1 osteoblasts on 3D biodegradable scaffolds. Mol. Biol. Cell 2002, 13, 345a.
[68]  Kretzmer, G.; Schügerl, K. Response of mammalian cells to shear stress. Appl. Microbiol. Biotechnol. 1991, 34, 613–616, doi:10.1007/BF00167909.

Full-Text

comments powered by Disqus

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133

WeChat 1538708413