Numerical Study on Parameters Affecting the Structure of Scaffolds Prepared by Freeze-Drying Method

Document Type: Research Article

Authors

Faculty of Polymer Engineering, Sahand University of Technology, Tabriz, I.R. IRAN

Abstract

Freeze-drying is one of the most used methods for preparing scaffolds and is very sensitive to the material and operational parameters such as nucleation temperature, thermal properties of the mold, cooling rate, set freezing point, and slurry height. In the present study, a Finite Element Method (FEM) based code was developed to investigate the effects of such parameters and to eventually predict the microstructure of the scaffold. Similar molds and cooling conditions used in various experimental studies were simulated and compared. The achieved pattern demonstrated how different thermal condition tailored scaffold microstructure. It was shown that nucleation temperature (Tn) was an effective parameter controlling the final structure of the scaffold and influenced pore sizes with different mold materials. Simulation results also showed that by decreasing the rate of cooling, the average pore sizes increased, and a quenching solution led to a randomly distributed pattern of pore sizes. It is also achieved that by increasing the set freezing temperature as well as the height of the solution the pore sizes increased more at the top of the mold. The thermal gradient also illustrated the orientation of the pore in a mold with the thick isolated wall was considerably uniform. This framework can be used to optimize the scaffold structure or any ice templating method.

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Main Subjects


[1] Chung H.J., Park T.G., Surface Engineered and Drug Releasing Pre-Fabricated Scaffolds for Tissue Engineering. Advanced Drug Delivery Reviews, 59(4): 249-262 (2007).
[2] O'Brien F.J., Biomaterials & Scaffolds for Tissue Engineering. Materials Today, 14 (3): 88-95 (2011).
[3] O’Brien F.J., Harley B.A., Yannas I.V., Gibson L., Influence of Freezing Rate on Pore Structure
in Freeze-Dried Collagen-GAG Scaffolds
, Biomaterials, 25 (6), 1077-1086 (2004).
[4] Madaghiele M., Sannino A., Yannas I.V., Spector M., Collagen‐Based Matrices with Axially Oriented Pores, Journal of Biomedical Materials Research Part A, 85 (3): 757-767 (2008).
[5] Alizadeh M., Abbasi F., Khoshfetrat A., Ghaleh H., Microstructure and Characteristic Properties of Gelatin/Chitosan Scaffold Prepared by a Combined Freeze-Drying/Leaching Method, Materials Science and Engineering: C, 33(7): 3958-3967 (2013).
[6] Davidenko N., Gibb T., Schuster C., Best S.M., Campbell J., Watson C., Cameron R.E., Biomimetic Collagen Scaffolds with Anisotropic Pore Architecture, Acta Biomaterialia, 8 (2): 667-676 (2012).
[7] 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 Engineering Part C: Methods, 16 (5): 887-894 (2009).
[8] Yuan N.-Y., Lin Y.-A., Ho M.-H., Wang D.-M., Lai J.-Y., Hsieh H.-J., Effects of the Cooling mode on the Structure and Strength of Porous Scaffolds Made of Chitosan, Alginate, and Carboxymethyl Cellulose by the Freeze-Gelation Method, Carbohydrate Polymers, 78 (2): 349-356 (2009).
[9] Tanthapanichakoon W., Tamon H., Nakagawa K., Charinpanitkul T., Synthesis of Porous Materials
and Their Microstructural Control through Ice Templating
. Engineering Journal, 17 (3): 1-8 (2013).
[10] Moore M.J., Friedman J.A., Lewellyn E.B., Mantila S.M., Krych A.J., Ameenuddin S., Knight A.M., Lu L., Currier B.L., Spinner R.J., Multiple-Channel Scaffolds to Promote Spinal Cord Axon Regeneration, Biomaterials, 27 (3): 419-429 (2006).
[11] Yannas I., Burke J., Orgill D., Skrabut E., Wound Tissue can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin, Science, 215 (4529): 174-176 (1982).
[12] Lee S.Y., Oh J.H., Kim J.C., Kim Y.H., Kim S.H., Choi J.W., In vivo Conjunctival Reconstruction Using Modified PLGA Grafts for Decreased Scar Formation and Contraction, Biomaterials, 24(27): 5049-5059 (2003).
[14] Berry C.C., Campbell G., Spadiccino A., Robertson M., Curtis A.S., The Influence of Microscale Topography on Fibroblast Attachment and Motility, Biomaterials, 25(26): 5781-5788 (2004).
[15] Woinet B., Andrieu J., Laurent M., Min S., Experimental and Theoretical Study of Model Food Freezing. Part II. Characterization and Modelling of the Ice Crystal Size, Journal of Food Engineering, 35(4): 395-407 (1998).
16] Pawelec K., Husmann A., Best S.M., Cameron R.E., Understanding Anisotropy and Architecture in Ice-Templated Biopolymer Scaffolds, Materials Science and Engineering: C,  (2014).
[17] Pawelec K., Husmann A., Best S.M., Cameron R.E., A Design protocol for tailoring ice-templated scaffold Structure, Journal of the Royal Society Interface, 11(92): 20130958 (2014).
[18] Kiani H., Sun D.-W., Water Crystallization and Its Importance to Freezing of Foods: A Review, Trends in Food Science & Technology, 22(8): 407-426 (2011).
[19] Lunardini, V.J., “Heat Transfer with Freezing and Thawing”, Elsevier: (1991).
[20] Moore E.B., Molinero V., Structural Transformation in Supercooled Water Controls the Crystallization Rate of Ice, Nature, 479(7374): 506-508 (2011).
[21] Nakagawa K., Hottot A., Vessot S., Andrieu J., Modeling of Freezing Step during Freeze‐Drying of Drugs in Vials, AIChE Journal, 53(5): 1362-1372 (2007).
[22] Saatchi, A., Seddiqi, H., Amoabediny, G., Helder, M.N., Zandieh-Doulabi, B., Klein-Nulend, J., Computational Fluid Dynamics in 3D-Printed Scaffolds with Different Strand-Orientation in Perfusion Bioreactors. Iranian Journal of Chemistry and Chemical Engineering (IJCCE), - (2019). [in Press]
[23] Muzzio C.R., Dini N.G., Simulation of Freezing Step in Vial Lyophilization Using Finite Element Method, Computers & Chemical Engineering, 35 (11): 2274-2283 (2011).
[24] Nakagawa, K., Thongprachan, N., Charinpanitkul, T., Tanthapanichakoon, W., Ice Crystal Formation
in the Carbon Nanotube Suspension: A Modelling Approach
, Chemical Engineering Science, 65 (4): 1438-1451 (2010).
[25] Quintero Ortega I.s.A., Mota-Morales J.D., Elizalde Peña E.A., Zárate-Triviño D.G., De Santiago Y.A., Ortiz A., García Gaitan B., Sanchez I.C., Luna-Bárcenas G., Cryogenic Process to Elaborate
Poly (ethylene glycol) Scaffolds. Experimental and Simulation Studies
. Industrial & Engineering Chemistry Research, 52 (2): 706-715 (2012).
[26] Chan K., Liang W., Francis W., Nicolella D., A Multiscale Modeling Approach to Scaffold Design and Property Prediction, Journal of the Mechanical Behavior of Biomedical Materials, 3(8): 584-593 (2010).
[27] Hollister S., Maddox R., Taboas J., Optimal Design and Fabrication of Scaffolds to Mimic Tissue Properties and Satisfy Biological Constraints, Biomaterials, 23(20): 4095-4103 (2002).
[28] Mehdizadeh H., Sumo S., Bayrak E.S., Brey E.M., Cinar A., Three-dimensional Modeling of Angiogenesis in Porous Biomaterial Scaffolds, Biomaterials, 34 (12): 2875-2887 (2013).
[29] Yu P., Lee T.S., Zeng Y., Low H.T., Fluid Dynamics and Oxygen Transport in a Micro-Bioreactor
with a Tissue Engineering Scaffold
, International Journal of Heat and Mass Transfer, 52 (1): 316-327 (2009).
[30] Youssef K., Mack J., Iruela‐Arispe M., Bouchard L.S., Macro‐Scale Topology Optimization for Controlling Internal Shear Stress in a Porous Scaffold Bioreactor, Biotechnology and Bioengineering, 109(7): 1844-1854 (2012).
[31] Kamalipour M., AliMousavi Dehghani S.A., Naseri A., Abbasi S., Distinguishing Anhydrate
and Gypsum Scale in Mixing Incompatible Surface and Ground Waters During Water Injection
Process
, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 37(1): 231-240
(2018).
[32] Jamshidi S., Bozorgmehry Boozarjomehry R., Pishvaie S.M.R., An Irregular Lattice Pore Network Model Construction Algorithm, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 29(1): 61-70 (2010).
[33] Ghaleh H., Abbasi F., Alizadeh M., Khoshfetrat A.B., Mimicking the Quasi-Random Assembly of Protein Fibers in the Dermis by Freeze-Drying Method, Materials Science and Engineering: C, 49: 807-815 (2015).
[34] Williams T.L., “An Experimental Investigation of Natural Convection Heat Transfer in a Refrigerator During Closed Door Conditions”; Air Conditioning and Refrigeration Center. College of Engineering, University of Illinois at Urbana-Champaign (1994).
[35] Shultz, M.J., Bisson, P.J., Brumberg, A., Best Face Forward: Crystal-Face Competition at the Ice-Water Interface, The Journal of Physical Chemistry B, 118(28): 7972–7980 (2014).
[36] Swope W.C., Andersen H.C., Berens P.H., Wilson K.R., A Computer Simulation Method for the Calculation of Equilibrium Constants for the Formation of Physical Clusters of Molecules: Application To Small Water Clusters, The Journal of Chemical Physics, 76(1): 637-649 (1982).