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Multiscale modelling and homogenisation of fibre-reinforced hydrogels for tissue engineering. (English) Zbl 1503.74027

Summary: Tissue engineering aims to grow artificial tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. A recent approach to engineer artificial cartilage involves seeding cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres combined with a cast or printed hydrogel, and subjecting the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how the applied load is distributed throughout the construct. To address this, we employ homogenisation theory to derive equations governing the effective macroscale material properties of a periodic, elastic-poroelastic composite. We treat the fibres as a linear elastic material and the hydrogel as a poroelastic material, and exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions) to derive macroscale equations governing the response of the composite to an applied load. This homogenised description reflects the orthotropic nature of the composite. To validate the model, solutions from finite element simulations of the macroscale, homogenised equations are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings and to determine the local mechanical environment experienced by cells embedded within the construct.

MSC:

74F10 Fluid-solid interactions (including aero- and hydro-elasticity, porosity, etc.)
74E30 Composite and mixture properties
74Q15 Effective constitutive equations in solid mechanics
74L15 Biomechanical solid mechanics

Software:

TetGen

References:

[1] (2013) Osteoarthritis in general practice: data and perspectives.
[2] Ateshian, G. (2007) On the theory of reactive mixtures for modeling biological growth. Biomech. Model. Mechanobiol. 6(6), 423-445.
[3] Auriault, J.-L. & Sanchez-Palencia, E. (1977) Etude du comportement macroscopique d’un milieu poreux saturé déformable. J. Méc. 16(4), 575-603. · Zbl 0382.73013
[4] Badia, S., Quaini, A. & Quarteroni, A. (2009) Coupling Biot and Navier-Stokes equations for modelling fluid-poroelastic media interaction. J. Comput. Phys. 228, 7986-8014. · Zbl 1391.74234
[5] Baker, S. R., Banerjee, S., Bonin, K. & Guthold, M. (2016) Determining the mechanical properties of electrospun poly-ɛ-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique. Mater. Sci. Eng. C59, 203-212.
[6] Bas, O., De-Juan-Pardo, E. M., Meinert, C., D’Angella, D., Baldwin, J. G., Bray, L. J., Wellard, R. M., Kollmannsberger, S., Rank, E., Werner, C., Klein, T. J., Catelas, I. & Hutmacher, D. W. (2017) Biofabricated soft network composites for cartilage tissue engineering. Biofabrication7, 025014.
[7] Biot, M. A. (1962) Generalized theory of acoustic propagation in porous dissipative media. J. Acoust. Soc. Am. 34(5), 1254-1264.
[8] Biot, M. A. (1972) Theory of finite deformations of porous solids. Indiana Univ. Math. J. 21, 597-620. · Zbl 0218.76090
[9] Bruna, M. & Chapman, S. J. (2015) Diffusion in spatially varying porous media. SIAM J. Appl. Math. 75(4), 1648-1674. · Zbl 1320.35038
[10] Bukac, M., Yotov, I., Zakerzadeh, R. & Zunino, P. (2015) Partitioning strategies for the interaction of a fluid with a poroelastic material based on a Nitsche’s coupling approach. Comput. Methods Appl. Mech. Eng. 292, 138-170. · Zbl 1423.76419
[11] Castilho, M., Feyen, D., Flandes-Iparraguirre, M., Hochleitner, G., Groll, J., Doevendans, P., Vermonden, T., Ito, K., Sluijter, J. & Malda, J. (2017) Melt electrospinning writing of poly-hydroxymethylglycolide-co-ɛ-caprolactone-based scaffolds for cardiac tissue engineering. Adv. Healthcare Mater. 6(18), 1700311.
[12] Castilho, M., Hochleitner, G., Wilson, W., Van Rietbergen, B., Dalton, D. P., Groll, J. & Malda, J. (2018) Mechanical behavior of a soft hydrogel reinforced with three-dimensional printed microfibre scaffolds. Sci. Rep. 8, 1245.
[13] Collis, J., Brown, D. L., Hubbard, M. E. & O’Dea, R. D. (2017) Effective equations governing an active poroelastic medium. Proc. R. Soc. A473, 20160755. · Zbl 1404.74040
[14] Davit, Y., Bell, C. G., Byrne, H. M., Chapman, L. A., Kimpton, L. S., Lang, G. E., Leonard, K. H., Oliver, J. M., Pearson, N. C., Shipley, R. J., Waters, S. L., Whiteley, J. P., Wood, B. D. & Quintard, M. (2013) Homogenization via formal multiscale asymptotics and volume averaging: how do the two techniques compare?Adv. Water Resour. 62, 178-206.
[15] Detournay, E. & Cheng, A. H. D. (1993) Fundamentals of poroelasticity, Reprint of Chapter 5. In: Comprehensive Rock Engineering: Principles, Practice and Projects. Analysis and Design Method, Vol. II. Pergamon Press, Oxford, UK.
[16] Dunlop, J. W. C. & Fratzl, P. (2015) Bioinspired composites: making a tooth mimic. Nat. Mater. 14, 1082-1083.
[17] Eschbach, F. O. & Huang, S. J. (1994) Hydrophilic-hydrophobic binary systems of poly (2-hydroxyethyl methacrylate) and polycaprolactone. Part I: Synthesis and characterization. J. Bioact. Compatible Polym. 9, 29-54.
[18] Eshraghi, S. & Das, S. (2010) Mechanical and microstructural properties of polycaprolactone scaffolds with one-dimensional, two-dimensional, and three-dimensional orthogonally oriented porous architectures produced by selective laser sintering. Acta Biomater. 6, 2467-2476.
[19] Gladman, A. S., Matsumoto, E. A., Nuzzo, R. G., Mahadevan, L. & Lewis, J. A. (2016) Biomimetic 4D printing. Nat. Mater. 15, 413-418.
[20] Goriely, A. & Amar, M. B. (2007) On the definition and modeling of incremental, cumulative, and continuous growth laws in morphoelasticity. Biomech. Model. Mechanobiol. 6(5), 289-296.
[21] Groll, J., Boland, T., Blunk, T., Burdick, J. A., Cho, D.-W., Dalton, P. D., Derby, B., Forgacs, G., Li, Q., Mironov, V. A., Moroni, L., Nakamura, M., Shu, W., Takeuchi, S., Vozzi, G., Woodfield, T. B. F., Xu, T., Yoo, J. J. & Malda, J. (2016) Biofabrication: reappraising the definition of an evolving field. Biofabrication8, 013001.
[22] Hang, S. (2015) TetGen, a Delaunay-based quality tetrahedral mesh generator. ACM Trans. Math. Softw. 41(2), Article 11. · Zbl 1369.65157
[23] Holzapfel, G. A. (2000) Nonlinear Solid Mechanics: A Continuum Approach for Engineering. Wiley, Chichester. · Zbl 0980.74001
[24] Howell, P., Kozyreff, G. & Ockendon, J. (2009) Applied Solid Mechanics. Cambridge University Press, Cambridge. · Zbl 1153.74003
[25] HydroZONES, Last accessed 1 October 2017. http://hydrozones.eu.
[26] Klika, V., Gaffney, E. A., Chen, Y.-C. & Brown, C. P. (2016) An overview of multiphase cartilage mechanical modelling and its role in understanding function and pathology. J. Mech. Behav. Biomed. Mater. 62, 139-157.
[27] Lemon, G., King, J. R., Byrne, H. M., Jensen, O. E. & Shakesheff, K. M. (2006) Mathematical modelling of engineered tissue growth using a multiphase porous flow mixture theory. J. Math. Bio52(5), 571-594. · Zbl 1110.92016
[28] Li, Z., Kupcsik, L., Yao, S.-J., Alini, M. & Stoddart, M. J. (2010) Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-β pathway. J. Cell. Mol. Med. 14(6A), 1338-1346.
[29] Mikelic, A. & Wheeler, M. F. (2012) On the interface law between a deformable porous medium containing a viscous fluid and an elastic body. Math. Models Methods Appl. Sci. 22, 1250031. · Zbl 1257.35030
[30] Mow, V., Kuei, S., Lai, W. & Armstrong, C. (1980) Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments. J. Biomech. Eng. 102(1), 73-84.
[31] Murad, M. A. & Loula, A. F. (1994) On stability and convergence of finite element approximations of Biot’s consolidation problem. Int. J. Numer. Methods Eng. 37, 645-667. · Zbl 0791.76047
[32] O’Dea, R. D., Waters, S. L. & Byrne, H. M. (2010) A multiphase model for tissue construct growth in a perfusion bioreactor. Math. Med. Biol. 27(2), 95-127. · Zbl 1190.92008
[33] Parnell, W. & Abrahams, I. (2008) Homogenization for wave propagation in periodic fibre-reinforced media with complex microstructure. i—theory. J. Mech. Phys. Solids67, 2521-2540. · Zbl 1171.74409
[34] Penta, R., Ambrosi, D. & Shipley, R. J. (2014) Effective governing equations for poroelastic growing media. Q. J. Mech. Appl. Math. 67, 69-91. · Zbl 1346.74159
[35] Peter, M. A. (2009) Coupled reaction-diffusion processes inducing an evolution of the microstructure: analysis and homogenization. Nonlinear Anal. Theory Methods Appl. 70, 806-821. · Zbl 1151.35308
[36] Piatnitski, A. & Ptashnyk, M. (2017) Homogenization of biomechanical models for plant tissues. Multiscale Model. Simul. 15(1), 339-387. · Zbl 1383.35019
[37] Ptashnyk, M. & Seguin, B. (2016) The impact of microfibril orientations on the biomechanics of plant cell walls and tissues. Bull. Math. Biol. 78, 2135-2164. · Zbl 1357.92006
[38] Shipley, R., Jones, G., Dyson, R., Sengers, B., Bailey, C., Catt, C., Please, C. & Malda, J. (2009) Design criteria for a printed tissue engineering construct: a mathematical homogenization approach. J. Theor. Biol. 259(3), 489-502. · Zbl 1402.92258
[39] Shipley, R. J. & Chapman, S. J. (2010) Multiscale modelling of fluid and drug transport in vascular tumours. Bull. Math. Biol. 72, 1464-1491. · Zbl 1198.92028
[40] Sunkara, V. & Von Kleist, M. (2016) Coupling cellular phenotype and mechanics to understand extracellular matrix formation and homeostasis in osteoarthritis. IFAC-PapersOnLine49(26), 038-043.
[41] Tan, E., Ng, S. & Lim, C. (2005) Tensile testing of a single ultrafine polymeric fiber. Biomaterials26, 1453-1456.
[42] Visser, J., Melchels, F. P. W., Jeon, J. E., Van Bussel, E. M., Kimpton, L. S., Byrne, H. M., Dhert, W. J. A., Dalton, P. D., Hutmacher, D. W. & Malda, J. (2015) Reinforcement of hydrogels using three-dimensionally printed microfibres. Nat. Commun. 6, 6933.
[43] Wegst, U. G. K., Ba, H., Saiz, E., Tomsia, A. P. & Ritchie, R. O. (2015) Bioinspired structural materials. Nat. Mater. 14, 23-26.
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