Abstract
Tissue engineered vascular grafts cultured in vitro are often done so under static conditions, which forces a diffusion-only mass transport regime for nutrient delivery and metabolite removal. Some bioreactor culture methods employ mechanical stimulation to improve material strength and stiffness; however, even with mechanical stimulation, engineered tissues are likely to operate in a diffusional transport regime for nutrient delivery and metabolite removal. In this study, we present an analysis of dissolved oxygen (DO) transport limitations that can arise in statically cultured vascular grafts and highlight bioreactor designs that improve transport, particularly by perfusion of medium through the interstitial space by transmural flow. A computational analysis is provided in conjunction with empirical data to support the models. Our goal was to investigate designs that would eliminate nutrient gradients that are evident using static culture methods in order to develop more uniform engineered vascular tissues, which could potentially improve mechanical strength and stiffness.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Jain, R.K., Au, P., Tam, J., Duda, D.G., Fukumura, D.: Engineering vascularized tissue. Nat. Biotechnol. 23, 821–823 (2005)
Malda, J., Rouwkema, J., Martens, D.E., le Comte, E.P., Kooy, F.K., Tramper, J., et al.: Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: measurement and modeling. Biotechnol. Bioeng. 86, 9–18 (2004)
Malda, J., Woodfield, T.B.F., van der Vloodt, F., Wilson, C., Martens, D.E., Tramper, J., et al.: The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage. Biomaterials 26, 63–72 (2005)
Nikolaev, N.I., Obradovic, B., Versteeg, H.K., Lemon, G., Williams, D.J.: A validated model of GAG deposition, cell distribution, and growth of tissue engineered cartilage cultured in a rotating bioreactor. Biotechnol. Bioeng. 105, 842–852 (2009)
Brown, D.A., MacLellan, W.R., Laks, H., Dunn, J.C.Y., Wu, B.M., Beygui, R.E.: Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue. Biotechnol. Bioeng. 97, 962–975 (2007)
Radisic, M., Malda, J., Epping, E., Geng, W.L., Langer, R., Vunjak-Novakovic, G.: Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol. Bioeng. 93, 332–343 (2006)
Potier, E., Ferreira, E., Meunier, A., Sedel, L., Logeart-Avramoglou, D., Petite, H.: Prolonged hypoxia concomitant with serum deprivation induces massive human mesenchymal stem cell death. Tissue Eng. 13, 1325–1331 (2007)
Demol, J., Lambrechts, D., Geris, L., Schrooten, J., Van Oosterwyck, H.: Towards a quantitative understanding of oxygen tension and cell density evolution in fibrin hydrogels. Biomaterials 32, 107–118 (2011)
Isenberg, B.C., Williams, C., Tranquillo, R.T.: Endothelialization and flow conditioning of fibrin-based media-equivalents. Ann. Biomed. Eng. 34, 971–985 (2006)
Webb, A.R., Macrie, B.D., Ray, A.S., Russo, J.E., Siegel, A.M., Glucksberg, M.R., et al.: In vitro characterization of a compliant biodegradable scaffold with a novel bioreactor system. Ann. Biomed. Eng. 35, 1357–1367 (2007)
Hahn, M.S., McHale, M.K., Wang, E., Schmedlen, R.H., West, J.L.: Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based tissue engineered vascular grafts. Ann. Biomed. Eng. 35, 190–200 (2007)
Butcher, J.T., Barrett, B.C., Nerem, R.M.: Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells in an engineered tissue model of the aortic wall. Biomaterials 27, 5252–5258 (2006)
Stegemann, J.P., Hong, H., Nerem, R.M.: Mechanical, biochemical, and extracellular matrix effects on vascular smooth muscle cell phenotype. J. Appl. Physiol. 98, 2321–2327 (2005)
Syedain, Z.H., Weinberg, J.S., Tranquillo, R.T.: Cyclic distension of fibrin-based tissue constructs: Evidence of adaptation during growth of engineered connective tissue. Proc. Natl. Acad. Sci. USA 105, 6537–6542 (2008)
Niklason, L.E., Gao, J., Abbott, W.M., Hirschi, K.K., Houser, S., Marini, R., et al.: Functional arteries grown in vitro. Science 284, 489–493 (1999)
Niklason, L.E., Abbott, W., Gao, J., Klagges, B., Hirschi, K.K., Ulubayram, K., et al.: Morphologic and mechanical characteristics of engineered bovine arteries. J. Vasc. Surg. 33, 628–638 (2001)
Williams, C., Wick, T.M.: Perfusion bioreactor for small diameter tissue-engineered arteries. Tissue Eng. 10, 930–941 (2004)
Khong, Y.M., Mang, J., Zhou, S.B., Cheung, C., Doberstein, K., Samper, V., et al.: Novel intra-tissue perfusion system for culturing thick liver tissue. Tissue Eng. 13, 2345–2356 (2007)
Radisic, M., Yang, L., Boublik, J., Cohen, R.J., Langer, R., Freed, L.E., et al.: Medium perfusion enables engineering of compact and contractile cardiac tissue. Am. J. Physiol. Heart Circ. Physiol. 286, H507–H516 (2004)
Radisic, M., Malda, J., Epping, E., Geng, W.L., Langer, R., Vunjak-Novakovic, G.: Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol. Bioeng. 93, 332–343 (2006)
Chung, C.A., Chen, C.W., Chen, C.P., Tseng, C.S.: Enhancement of cell growth in tissue-engineering constructs under direct perfusion: modeling and simulation. Biotechnol. Bioeng. 97, 1603–1616 (2007)
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. 93, 947–954 (2006)
Bjork, J.W., Tranquillo, R.T.: Transmural flow bioreactor for vascular tissue engineering. Biotechnol. Bioeng. 104, 1197–1206 (2009)
Syedain, Z.H., Meier, L.A., Bjork, J.W., Lee, A., Tranquillo, R.T.: Implantable arterial grafts from human fibroblasts and fibrin using a multi-graft pulsed flow-stretch bioreactor with noninvasive strength monitoring. Biomaterials 32, 714–722 (2011)
Chung, C.A., Chen, C.W., Chen, C.P., Tseng, C.S.: Enhancement of cell growth in tissue-engineering constructs under direct perfusion: modeling and simulation. Biotechnol. Bioeng. 97, 1603–1616 (2007)
Wang, S., Tarbell, J.M.: Effect of fluid flow on smooth muscle cells in a 3-dimensional collagen gel model. Arterioscler. Thromb. Vasc. Biol. 20, 2220–2225 (2000)
Papas, K.K., Pisania, A., Wu, H., Weir, G.C., Colton, C.K.: A stirred microchamber for oxygen consumption rate measurements with pancreatic islets. Biotechnol. Bioeng. 98, 1071–1082 (2007)
Avgoustiniatos, E.: Oxygen diffusion limitation in pancreatic islet culture and immunoisolation. Massachusetts Institute of Technology, Cambridge (2001)
Tschoeke, B., Flanagan, T.C., Koch, S., Harwoko, M.S., Deichmann, T., Ella, V., et al.: Tissue-engineered small-caliber vascular graft based on a novel biodegradable composite fibrin-polylactide scaffold. Tissue eng. 15, 1909–1918 (2009)
Hoerstrup, S.P., Zund, G., Sodian, R., Schnell, A.M., Grunenfelder, J., Turina, M.I.: Tissue engineering of small caliber vascular grafts. Eur. J. Cardiothorac. Surg. 20, 164–169 (2001)
Seliktar D., Black R.A., Vito R.P., Nerem R.M.: Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro. Ann. Biomed. Eng. 28, 351–362 (2000)
Simpson, N.E., Han, Z.C., Berendzen, K.M., Sweeney, C.A., Oca-Cossio, J.A., Constantinidis, I., et al.: Magnetic resonance spectroscopic investigation of mitochondrial fuel metabolism and energetics in cultured human fibroblasts: Effects of pyruvate dehydrogenase complex deficiency and dichloroacetate. Mol. Genet. Metab. 89, 97–105 (2006)
Decker, S., Lipmann, F.: Transport of d-glucose by membrane vesicles from normal and avian sarcoma virus transformed chicken embryo fibroblasts. Proc. Natl. Acad. Sci. USA 78, 5358–5361 (1981)
Truskey, G.A., Yuan, F., Katz, D.F.: Transport Phenomena in Biological Systems. Pearson Prentice Hall, Upper Saddle River (2004)
Weind, K.L., Boughner, D.R., Rigutto, L., Ellis, C.G.: Oxygen diffusion and consumption of aortic valve cusps. Am. J. Physiol.-Heart Circ. Physiol. 281, H2604–H2611 (2001)
Rong, Z., Cheema, U., Vadgama, P.: Needle enzyme electrode based glucose diffusive transport measurement in a collagen gel and validation of a simulation model. Analyst 131, 816–821 (2006)
Dean, J.A.: Lange’s Handbook of Chemistry (15th Edition), 15th edn. McGraw Hill, New York (1999)
Lee, J.: Biochemical Engineering. Prentice Hall, Englewood Cliffs, NJ (1991)
Invitrogen Life Technologies. http://products.invitrogen.com/ivgn/product/21063029#coa. Accessed 14 April 2011
Acknowledgments
This work has been supported by National Institutes of Health (NHLBI R01 HL083880 to RTT) and 3M Company (JWB). Furthermore, the technical assistance of Naomi Ferguson and Lee Meier is gratefully acknowledged as well as Dave Hultman for his efforts in machining and design discussions.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Bjork, J.W., Safonov, A.M., Tranquillo, R.T. (2012). Oxygen Transport in Bioreactors for Engineered Vascular Tissues. In: Geris, L. (eds) Computational Modeling in Tissue Engineering. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8415_2012_133
Download citation
DOI: https://doi.org/10.1007/8415_2012_133
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-32562-5
Online ISBN: 978-3-642-32563-2
eBook Packages: EngineeringEngineering (R0)