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An in silico bioreactor for simulating laboratory experiments in tissue engineering

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Abstract

This paper presents a software framework for the computational modeling of tissue engineering experiments, aimed to supplement and extend the empirical techniques currently employed in tissue engineering. The code included a model of cell population dynamics coupled to a finite element model of oxygen diffusion and consumption at the macroscale level, including the scaffold and the culture medium, and at the level of the scaffold microarchitecture. Cells were modeled as discrete entities moving in a continuum space, under the action of adhesion and repulsion forces. Oxygen distribution was calculated with the transient diffusion equation; oxygen consumption by cells was modeled by using the Michaelis–Menten equation. Other phenomena that can be formulated as a differential problem could be added in a straightforward manner to the code, due to the use of a general purpose finite element library. Two scaffold geometries were considered: a fiber scaffold and a scaffold with interconnected spherical pores. Cells were predicted to form clusters and adhere to the scaffold walls. Although the code demonstrated the ability to provide a robust performance, a calibration of the parameters employed in the model, based on specific laboratory experiments, is now required to verify the reliability of the results.

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References

  • F. Boschetti, M.T. Raimondi, F. Migliavacca, G. Dubini, Prediction of the micro-fluid dynamic environment imposed to three-dimensional engineered cell systems in bioreactors J. Biomech. 39(3), 418–425 (2006)

    Google Scholar 

  • S.E. Carver, C.A. Heath, Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure. Biotechnol. Bioeng. 63(2), 166–174(1999)

    Article  Google Scholar 

  • G. Cheng, B.B. Youssef, P. Markenscoff, K. Zygourakis, Cell population dynamics modulate the rates of tissue growth processes Biophys. J. 90(3), 713–724 (2006)

    Article  Google Scholar 

  • C.A. Chung, T.W. Yang, C.W. Chen, Analysis of cell growth and diffusion in a scaffold for cartilage tissue engineering Biotechnol. Bioeng. 94(6), 1138–1146 (2006)

    Article  Google Scholar 

  • C.A. Chung, C.W. Chen, C.P. Chen, C.S. Tseng, Enhancement of cell growth in tissue-engineering constructs under direct perfusion: Modeling and simulation Biotechnol. Bioeng. 97(6), 1603–1616 (2007)

    Article  Google Scholar 

  • M. Cioffi, F. Boschetti, M.T. Raimondi, G. Dubini, Modeling evaluation of the fluid-dynamic microenvironment in tissue-engineered constructs: A micro-CT based model. Biotechnol. Bioeng. 93(3), 500–510 (2006)

    Article  Google Scholar 

  • J.T. Connelly, E.J. Vanderploeg, M.E. Levenston, The influence of cyclic tension amplitude on chondrocyte matrix synthesis: Experimental and finite element analyses Biorheology 41(3–4), 377–387 (2004)

    Google Scholar 

  • M.A. DiMicco, R.L. Sah, Dependence of cartilage matrix composition on biosynthesis, diffusion, and reaction Transp. Porous Media 50, 57–73 (2003)

    Article  Google Scholar 

  • J.C. Dunn, W.Y. Chan, V. Cristini, J.S. Kim, J. Lowengrub, S. Singh, B.M. Wu, Analysis of cell growth in three-dimensional scaffolds Tissue Eng. 12(4), 705–716 (2006)

    Article  Google Scholar 

  • H.B. Frieboes, X. Zheng, C.H. Sun, B. Tromberg, R. Gatenby, V. Cristini, An integrated computational/experimental model of tumor invasion Cancer Res. 66(3), 1597–1604 (2006)

    Article  Google Scholar 

  • F. Galbusera, M. Cioffi, M.T. Raimondi, R. Pietrabissa, Computational modeling of combined cell population dynamics and oxygen transport in engineered tissue subject to interstitial perfusion Comp. Meth. Biomech. Biomed. Eng. 10(4), 279–287 (2007)

    Article  Google Scholar 

  • J.C. Haselgrove, I.M. Shapiro, S.F. Silverton, Computer modeling of the oxygen supply and demand of cells of the avian growth cartilage Am J Physiol 265(2 Pt 1), C497–C506 (1993)

    Google Scholar 

  • E.F. Keller, L.A. Segel, Model for chemotaxis J Theor Biol 30(2), 225–234 (1971)

    Article  Google Scholar 

  • B.S. Kirk, J.W. Peterson, R.H. Stogner, G.F. Carey, libMesh: a C++ library for parallel adaptive mesh refinement/coarsening simulations Eng. Comput. 22(3), 237–254 (2006)

    Article  Google Scholar 

  • R. Langer, J.P. Vacanti, Tissue Eng. Sci. 260(5110), 920–926 (2003)

    Google Scholar 

  • Y. Lee, S. Kouvroukoglou, L.V. McIntire, K. Zygourakis, A cellular automaton model for the proliferation of migrating contact-inhibited cells Biophys. J. 69(4), 1284–1298 (1995)

    Article  Google Scholar 

  • G. Lemon, J.R. King, H.M. Byrne, O.E. Jensen, K.M. Shakesheff, Mathematical modelling of engineered tissue growth using a multiphase porous flow mixture theory J. Math. Biol. 52(5), 571–594 (2006)

    Article  MATH  MathSciNet  Google Scholar 

  • A. Marsano, D. Wendt, R. Raiteri, R. Gottardi, M. Stolz, D. Wirz, A.U. Daniels, D. Salter, M. Jakob, T.M. Quinn, I. Martin, Use of hydrodynamic forces to engineer cartilaginous tissues resembling the non-uniform structure and function of meniscus Biomaterials 27(35), 5927–5934 (2006)

    Article  Google Scholar 

  • B. Obradovic, R.L. Carrier, G. Vunjak-Novakovic, L.E. Freed, Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage Biotechnol. Bioeng. 63(2), 197–205 (1999)

    Article  Google Scholar 

  • B. Obradovic, J.H. Meldon, L.E. Freed, G. Vunjak-Novakovic, Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model AIChE J. 46(9), 1860–1871 (2000)

    Article  Google Scholar 

  • E. Palsson, H.G. Othmer, A model for individual and collective cell movement in Dictyostelium discoideum Proc. Natl. Acad. Sci. U. S. A. 97(19), 10448–10453 (2000)

    Article  Google Scholar 

  • E. Palsson, A three-dimensional model of cell movement in multicellular systems Future Gener. Comput. Syst. 17, 835–852 (2001)

    Article  MATH  Google Scholar 

  • B. Porter, R. Zauel, H. Stockman, R. Guldberg, D. Fyhrie, 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor J. Biomech. 38(3), 543–549 (2005)

    Article  Google Scholar 

  • M. Radisic, W. Deen, R. Langer, G. Vunjak-Novakovic, Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers Am. J. Physiol. Heart Circ. Physiol. 288(3), H1278–H1289 (2005)

    Article  Google Scholar 

  • M.T. Raimondi, F. Boschetti, L. Falcone, F. Migliavacca, A. Remuzzi, G. Dubini, The effect of media perfusion on three-dimensional cultures of human chondrocytes: integration of experimental and computational approaches Biorheology 41(3–4), 401–410 (2004)

    Google Scholar 

  • S. Sanga, H.B. Frieboes, X. Zheng, R. Gatenby, E.L. Bearer, V. Cristini, Predictive oncology: a review of multidisciplinary, multiscale in silico modeling linking phenotype, morphology and growth Neuroimage 37(1), S120–S134 (2007)

    Article  Google Scholar 

  • J.L. Semple, N. Woolridge, C.J. Lumsden, In vitro, in vivo, in silico: computational systems in tissue engineering and regenerative medicine Tissue Eng. 11(3–4), 341–356 (2005)Review

    Article  Google Scholar 

  • B.G. Sengers, C.C. Van Donkelaar, C.W. Oomens, F.P. Baaijens, The local matrix distribution and the functional development of tissue engineered cartilage, a finite element study Ann. Biomed. Eng. 32(12), 1718–1727 (2004)

    Article  Google Scholar 

  • B.G. Sengers, M. Taylor, C.P. Please, R.O. Oreffo, Computational modelling of cell spreading and tissue regeneration in porous scaffolds Biomaterials 28(10), 1926–1940 (2007)Review

    Article  Google Scholar 

  • H. Singh, S.H. Teoh, H.T. Low, D.W. Hutmacher, Flow modeling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation J. Biotechnol. 119, 181–196 (2005)

    Article  Google Scholar 

  • K.A. Williams, S. Saini, T.M. Wick, Computational fluid dynamics modeling of steady-state momentum and mass transport in a bioreactor for cartilage tissue engineering Biotechnol. Prog. 18(5), 951–963 (2002)

    Article  Google Scholar 

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Correspondence to Fabio Galbusera.

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Galbusera, F., Cioffi, M. & Raimondi, M.T. An in silico bioreactor for simulating laboratory experiments in tissue engineering. Biomed Microdevices 10, 547–554 (2008). https://doi.org/10.1007/s10544-008-9164-9

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