Computational Fluid Dynamics in 3D-Printed Scaffolds with Different Strand-Orientation in Perfusion Bioreactors

Document Type : Research Article

Authors

1 School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, I.R. IRAN

2 Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, I.R. IRAN

3 Department Oral and Maxillofacial Surgery, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam Movement Sciences, Amsterdam, THE NETHERLANDS

4 Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA)-the University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, THE NETHERLANDS

10.30492/ijcce.2019.35867

Abstract

Bone tissue engineering strategies use fluid flow dynamics inside 3D-scaffolds in perfusion, bioreactors mechanically stimulate cells in these scaffolds. Fluid flow dynamics depends on the bioreactor’s inlet flow rate and 3D-scaffold architecture. We aimed to employ a computational evaluation to assess fluid dynamics in 3D-printed scaffolds with different angular orientations between strands in each layer inside a perfusion bioreactor at different inlet flow rates. 3D-printed cubic scaffolds (0.6×0.6×0.6 cm; total volume 216×10-3 cm3) containing strands (diameter 100 µm) with regular internal structure and different angular orientation (30°, 45°, 60°, and 90° between strands in each layer) were used for modeling. The finite element method showed that the perfusion bioreactor’s inlet flow rate (0.02, 0.1, 0.5 mL/min) was linearly related to average fluid velocity, average fluid shear stress, and average wall shear stress inside 3D-printed scaffolds with different angular orientation (30°, 45°, 60°, 90°) between strands in each layer. At all inlet flow rates, strands at 30° angular orientation increased average fluid velocity (1.2-1.5-fold), average fluid shear stress (6-10-fold), and average wall shear stress (1.4-2-fold) compared to strands at 45°, 60°, and 90° angular orientation providing similar results. In conclusion, significant local changes in fluid dynamics inside 3D-printed scaffolds result from varying the degree of angular orientation between strands in each layer, and the perfusion bioreactor’s inlet flow rate. By decreasing the angular orientation between strands in each layer and increasing the inlet flow rate of a perfusion bioreactor, the magnitude and distribution of fluid velocity, fluid shear stress, and wall shear stress inside the scaffold increased. The average fluid velocity, average fluid shear stress, and average wall shear stress inside the scaffold within the bioreactor increased linearly with the inlet flow rate. This might have important implications for bone tissue engineering strategies using cells, scaffolds, and bioreactors.

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Main Subjects


[1] Volkmer E., Drosse I., Otto S., Stangelmayer 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, 14(8): 1331-1340 (2008).
[2] Bjerre L., Bünger C.E., Kassem M., Mygind T., Flow Perfusion Culture of Human Mesenchymal Stem Cells on Ailicate-Substituted Tricalcium Phosphate Scaffolds, Biomaterials, 29(17): 2616-2627 (2008).
[4] Cai D.X., Quan Y., He P.J., Tan H.B., Xu Y.Q., Dynamic Perfusion Culture of Human Outgrowth Endothelial Progenitor Cells on Demineralized Bone Matrix in Vitro, Med. Sci. Monit., 22: 4037-4045 (2016).
[5]    Kim J., Ma T., Perfusion Regulation of HMSC Microenvironment and Osteogenic Differentiation in 3D Scaffold, Biotechnol. Bioeng., 109(1): 252-261 (2012).
[6] Liu C., Abedian R., Meister R., Haasper C., Hurschler C., Krettek C., Von Lewinski G., Jagodzinski M., Influence of Perfusion and Compression on the Proliferation and Differentiation of Bone Mesenchymal Stromal Cells Seeded on Polyurethane Scaffolds, Biomaterials, 33(4):1052-1064 (2012).
[7] Cartmell S.H., Porter B.D., García A.J., Guldberg, R.E., Effects of Medium Perfusion Rate on Cell-Seeded Three-dimensional Bone Constructs in Vitro, Tissue Eng., 9(6): 1197-1203 (2003).
[8] Sittichockechaiwut A., Scutt A.M., Ryan A.J., Bonewald, L.F., Reilly G.C., Use of Rapidly Mineralising Osteoblasts and Short Periods of Mechanical Loading to Accelerate Matrix Maturation in 3D Scaffolds, Bone, 44(5): 822-829 (2009).
[9] Bacabac R.G., Smit T.H., Mullender M.G., Dijcks S.J., Van Loon J.J., Klein-Nulend J., Nitric Oxide Production by Bone Cells is Fluid Shear Stress Rate Dependent, Biochem. Biophys. Res. Commun., 315(4): 823-829 (2004).
[10] Klein-Nulend J., Van der Plas A., Semeins C.M., Ajubi N.E., Frangos J.A., Nijweide P.J., Burger E.H., Sensitivity of Osteocytes to Biomechanical Stress in Vitro, FASEB J., 9(5): 441-445 (1995).
[11] Rubin J., Rubin C., Jacobs C.R., Molecular Pathways Mediating Mechanical Signaling in Bone, Gene, 367:1-16 (2006).
[12] Weinbaum S., Cowin S.C., Zeng Y., A Model for the Excitation of Osteocytes by Mechanical Loading-induced Bone Fluid Shear Stresses, J. Biomech., 27(3): 339-360 (1994).
[13] Song M.J., Dean D., Tate M.L.K., Mechanical Modulation of Nascent Stem Cell Lineage Commitment in Tissue Engineering Scaffolds, Biomaterials, 34(23): 5766-5775 (2013).
[14] Yue D., Zhang M., Lu J., Zhou J., Bai Y., Pan J., The Rate of Fluid Shear Stress is a Potent Regulator for the Differentiation of Mesenchymal Stem Cells, J. Cell. Physiol., (2019).
[15] Papantoniou I., Chai Y.C., Luyten F.P., Schrooten J., Process Quality Engineering for Bioreactor-driven Manufacturing of Tissue-engineered  Constructs for Bone Regeneration, Tissue Eng. Part C Methods, 19(8): 596-609 (2013).
[16] Elashry M.I., Gegnaw S.T., Klymiuk M.C., Wenisch S., Arnhold S., Influence of Mechanical Fluid Shear Stress on the Osteogenic Differentiation Protocols for Equine Adipose Tissue-Derived Mesenchymal Stem Cells, Acta Histochem., 121(3): 344-353 (2019).
[17] Li Y., Fang X., Jiang T., Minimally Traumatic Alveolar Ridge Augmentation with a Tunnel Injectable Thermo-sensitive Alginate Scaffold, J. Appl. Oral. Sci., 23(2): 215-223 (2015).
[19] Liu S., He Z., Xu G., Xiao X., Fabrication of Polycaprolactone Nanofibrous Scaffolds by Facile Phase Separation Approach, Mater. Sci. Eng. C Mater. Biol. Appl., 44: 201-208 (2014).
[20] Haugh M.G., Murphy C.M., O'Brien F.J., Novel Freeze-drying Methods to Produce a Range of Collagen-glycosaminoglycan Scaffolds with Tailored Mean Pore Sizes, Tissue Eng. Part C Methods, 16(5):887-94 (2010).
[21] Hollister S.J., Porous Scaffold Design for Tissue Engineering, Nat. Mater., 4(7):518-524 (2005).
[22] Stevens B., Yang Y., Mohandas A., Stucker B., Nguyen K.T., A Review of Materials, Fabrication Methods, and Strategies Used to Enhance Bone Regeneration in Engineered Bone Tissues, J. Biomed. Mater. Res. B Appl. Biomater., 85(2):573-582 (2008).
[24] Pfister A., Landers R., Laib A., Hübner U., Schmelzeisen R., Mülhaupt R., Biofunctional Rapid Prototyping for Tissue‐engineering Applications: 3D Bioplotting Versus 3D Printing, J. Polym. Sci. Pol. Chem., 42(3): 624-638 (2004).
[25] Bartnikowski M., Klein T.J., Melchels F.P., Woodruff M.A., Effects of Scaffold Architecture on Mechanical Characteristics and Osteoblast Response to Static and Perfusion Bioreactor Cultures, Biotechnol. Bioeng., 111(7): 1440-1451 (2014).
[26] Hossain M.S., Boergstrom D.J., Chen X.B., Prediction of Cell Growth Rate over Scaffold Strands inside a Perfusion Bioreactor, Biomech. Model. Mechanobiol., 14(2): 333-44 (2015).
[27] Lesman A., Blinder Y., Levenberg S., Modeling of Flow-induced Shear Stress Applied on 3D Cellular Scaffolds: Implications for Vascular Tissue Engineering, Biotechnol. Bioeng., 105(3):645-54 (2010).
[28] Hutmacher D.W., Singh H., Computational Fluid Dynamics for Improved Bioreactor Design and 3D Culture, Trends Biotechnol., 26(4): 166-72 (2008).
[29] Boschetti F., Raimondi M.T., Migliavacca F., Dubini G., Prediction of the Micro-fluid Dynamic Environment Imposed to Three-dimensional Engineered Cell Systems in Bioreactors, J. Biomech., 39(3): 418-25 (2006).
[30] Maes F., Claessens T., Moesen M., Van Oosterwyck H., Van Ransbeeck P., Verdonck P., Computational Models for Wall Shear Stress Estimation in Scaffolds: a Comparative Study of Two Complete Geometries, J. Biomech., 45(9): 1586-92 (2012).
[31] Vossenberg P., Higuera G.A., Van Straten G., Van Blitterswijk C.A., Van Boxtel A.J.B., Darcian Permeability Constant as Indicator for Shear Stresses in Regular Scaffold Systems for Tissue Engineering, Biomech. Model. Mechanobiol., 8(6): 499-507 (2009).
[32] Xue X., Patel M.K., Kersaudy-Kerhoas M., Desmulliez M.P., Bailey C., Topham D., Analysis of Fluid Separation in Microfluidic T-channels, Appl. Math. Model., 36(2): 743-755 (2012).
[33] McCoy R.J., Jungreuthmayer C., O'Brien F.J., Influence of Flow Rate and Scaffold Pore Size on Cell Behavior During Mechanical Stimulation in a Flow Perfusion Bioreactor, Biotechnol. Bioeng., 109(6): 1583-9154 (2012).
[35] Bakker A.D., Gakes T., Hogervorst J.M., De Wit G.M., Klein‐Nulend J., Jaspers R.T., Mechanical Stimulation and IGF-1 Enhance mRNA Translation Rate in Osteoblasts via Activation of the AKT-mTOR Pathway, J. Cell. Physiol., 231(6):1283-1290 (2016).
[36] Knippenberg M., Helder M.N., Zandieh Doulabi B., Semeins C.M., Wuisman P.I., Klein-Nulend J., Adipose Tissue-Derived Mesenchymal Stem Cells Acquire Bone Cell-like Responsiveness to Fluid Shear Stress on Osteogenic Stimulation, Tissue Eng., 11(11-12):1780-1788 (2005).
[37] Wittkowske C., Reilly G.C., Lacroix D., Perrault C.M., In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation, Front. Bioeng. Biotechnol., 4:87 (2016).
[38] Olivares A.L., Marsal È., Planell J.A., Lacroix D., Finite Element Study of Scaffold Architecture Design and Culture Conditions for Tissue Engineering, Biomaterials, 30(30):6142-6149 (2009).
[39] Prendergast P.J., Huiskes R., Soballe K., Biophysical Stimuli on Cells During Tissue Differentiation at Implant Interfaces, J. Biomech., 30(6):539-548 (1997).
[40] Park J., Li Y., Berthiaume F., Toner M., Yarmush M.L., Tilles A.W., Radial Flow Hepatocyte Bioreactor Using Stacked Microfabricated Grooved Substrates, Biotechnol. Bioeng., 99(2): 455-467 (2008).
[41] Tilles A.W., Baskaran H., Roy P., Yarmush M.L., Toner M., Effects of Oxygenation and Flow on the Viability and Function of Rat Hepatocytes Cocultured in a Microchannel Flat‐plate Bioreactor, Biotechnol. Bioeng., 73(5): 379-389 (2001).
[42] Vinci B., Duret C., Klieber S., Gerbal‐Chaloin S., Sa‐Cunha A., Laporte S., Suc B., Maurel P., Ahluwalia A., Daujat‐Chavanieu M., Modular Bioreactor for Primary Human Hepatocyte Culture: Medium Flow Stimulates Expression and Activity of Detoxification Genes, Biotechnol. J., 6(5): 554-564 (2011).
[43] Sandino C., Planell J.A., Lacroix D., A Finite Element Study of Mechanical Stimuli in Scaffolds for Bone Tissue Engineering, J. Biomech., 41(5): 1005-1014 (2008).
[44] Yan X., Chen X., Bergstrom D.J., Modeling of the Flow within Scaffolds in Perfusion BioreactorsAm. J. Biomed. Eng., 1(2):72-77 (2011).
[46] Yap C.H., Saikrishnan N., Yoganathan A.P., Experimental Measurement of Dynamic Fluid Shear Stress on the Ventricular Surface of the Aortic Valve Leaflet, Biomech. Model. Mechanobiol., 11(1-2): 231-244 (2012).
[47] Roloff C., Berg P., Redel T., Janiga G., Thévenin D., Tomographic Particle Image Velocimetry for the Validation of Hemodynamic Simulations in an Intracranial Aneurysm, Conf. Proc. IEEE Eng. Med. Biol. Soc., 2017: 1340-1343 (2017).