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Quantitative intravoxel analysis of microCT-scanned resorbing ceramic biomaterials – Perspectives for computer-aided biomaterial design

Published online by Cambridge University Press:  09 December 2014

Agnes Czenek ,
Romane Blanchard ,
Alexander Dejaco ,
Ólafur E. Sigurjónsson ,
Gissur Örlygsson ,
Paolo Gargiulo  and
Christian Hellmich
Agnes Czenek
Affiliation:
Institute for Mechanics of Materials and Structures, Vienna University of Technology (TU Wien), Austria; Institute of Biomedical and Neural Engineering, Reykjavik University, Iceland; and Department of Science, Landspitali University Hospital, Iceland
Romane Blanchard
Affiliation:
Institute for Mechanics of Materials and Structures, Vienna University of Technology (TU Wien), Austria
Alexander Dejaco
Affiliation:
Institute for Mechanics of Materials and Structures, Vienna University of Technology (TU Wien), Austria
Ólafur E. Sigurjónsson
Affiliation:
Institute of Biomedical and Neural Engineering, Reykjavik University, Iceland; and REModel Lab, The Blood Bank, Landspitali University Hospital, Iceland
Gissur Örlygsson
Affiliation:
Department of Materials, Biotechnology and Energy, Innovation Center Iceland, Iceland
Paolo Gargiulo
Affiliation:
Institute of Biomedical and Neural Engineering, Reykjavik University, Iceland; and Department of Science, Landspitali University Hospital, Iceland
Christian Hellmich*
Affiliation:
Institute for Mechanics of Materials and Structures, Vienna University of Technology (TU Wien), Austria
*
a)Address all correspondence to this author. e-mail: christian.hellmich@tuwien.ac.at
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Abstract

Driving the field of micro computed tomography toward more quantitative, rather than qualitative, approaches, we here present a new evaluation method, which uses the unique linear relationship between gray values and x-ray attenuation coefficients, together with the energy-dependence of the latter, to identify (i) the average x-ray energy used in the CT device, (ii) the x-ray attenuation coefficients, and (iii), via the x-ray attenuation average rule, the intravoxel composition, i.e., the microporosity, which, amongst others, governs the voxel-specific mechanical properties, such as stiffness and strength. The method is realized for six 3D tricalcium phosphate scaffolds, seeded with pre-osteoblastic cells and differentiated for 3, 6, and 8 weeks, respectively. The corresponding voxel-specific microporosities turn out to increase during the culturing period (resulting in reduced elastic properties, as determined from micromechanical considerations), while the overall macroporosity remains constant. The new methods are expected to further foster the development of a rationally based and computer-aided design of biomaterials and tissue engineering scaffolds.

Keywords

tissue engineering scaffoldcontinuum micromechanicscomputed tomographyx-ray physicsbone biomaterialstricalcium phosphate
Type
Invited Feature Papers
Information
Journal of Materials Research , Volume 29 , Issue 23 , 14 December 2014 , pp. 2757 - 2772
Copyright
Copyright © Materials Research Society 2014 

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References

REFERENCES

Ho, S.T. and Hutmacher, D.W.: A comparison of micro CT with other techniques used in the characterization of scaffolds. Biomaterials 27(8), 1362 (2006).Google Scholar
Renghini, C., Komlev, V., Fiori, F., Verné, E., Baino, F., and Vitale-Brovarone, C.: Micro-CT studies on a 3D bioactive glass-ceramic scaffolds for bone regeneration. Acta Biomater. 5(4), 1328 (2009).Google Scholar
Gauthier, O., Müller, R., von Stechow, D., Lamy, B., Weiss, P., Bouler, J-M., Aguado, E., and Daculsi, G.: In vivo bone regeneration with injectable calcium phosphate biomaterial: A three-dimensional micro-computed tomographic, biomechanical and SEM study. Biomaterials 26(27), 5444 (2005).CrossRefGoogle ScholarPubMed
Cedola, R., Giuliani, A., Komlev, A., Lagomarsino, V., Mastrogiacomo, S., Peyrin, M., Rustichelli, F., and Cancedda, F.: Bulk and interface investigations of scaffolds and tissue-engineered bones by x-ray microtomography and x-ray microdiffraction. Biomaterials 28(15), 2505 (2007).Google Scholar
Jones, A.C., Arns, C.H., Sheppard, A.P., Hutmacher, D.W., Milthorpe, B.K., and Knackstedt, M.A.: Assessment of bone ingrowth into porous biomaterials using micro-CT. Biomaterials 28(15), 2491 (2007).Google Scholar
Jaecques, S.V.N., Van Oosterwyck, H., Muraru, L., Van Cleynenbreugel, T., De Smet, E., Wevers, M., Naert, I., and Vander Sloten, J.: Individualised, micro CT-based finite element modelling as a tool for biomechanical analysis related to tissue engineering of bone. Biomaterials 25(9), 1683 (2004).Google Scholar
Scheiner, S., Sinibaldi, R., Pichler, B., Komlev, V., Renghini, C., Vitale-Brovarone, C., Rustichelli, F., and Hellmich, C.: Micromechanics of bone tissue-engineering scaffolds, based on resolution error-cleared computer tomography. Biomaterials 30(12), 2411 (2009).Google Scholar
Truscello, S., Kerckhofs, G., Van Bael, S., Pyka, G., Schrooten, J., and Van Oosterwyck, H.: Prediction of permeability of regular scaffolds for skeletal tissue engineering: A combined computational and experimental study. Acta Biomater. 8(4), 1648 (2012).Google Scholar
Dias, M.R., Fernandes, P.R., Guedes, J.M., and Hollister, S.J.: Permeability analysis of scaffolds for bone tissue engineering. J. Biomech. 45(6), 938 (2012).CrossRefGoogle ScholarPubMed
Sandino, C., Checa, S., Prendergast, P.J., and Lacroix, D.: Simulation of angiogenesis and cell differentiation in a CaP scaffold subjected to compressive strains using a lattice modeling approach. Biomaterials 31(8), 2446 (2010).CrossRefGoogle Scholar
Sandino, C. and Lacroix, D.: A dynamical study of the mechanical stimuli and tissue differentiation within a CaP scaffold based on micro-CT finite element models. Biomech. Model. Mechanobiol. 10(4), 565 (2011).Google Scholar
Hubbel, J.H. and Seltzer, S.M.: Tables of X-ray Mass Attenuation Coefficients and Mass Energy-Absorption Coefficients from 1 keV to 20 MeV for Elements Z = 1 to 92 and 48 Additional Substances of Dosimetric Interest (National Institute of Standards and Technologies, July 2004). http://www.nist.gov/pml/data/xraycoef/index.cfm.Google Scholar
Seltzer, S.M.: Calculation of photon mass energy-transfer and mass energy-absorption coefficients. Radiat. Res. 136(2), 147 (1993).Google Scholar
Hubbel, J.H.: Photon mass attenuation and energy-absorption coefficients. Int. J. Appl. Radiat. Isot. 33(11), 1269 (1982).Google Scholar
Crawley, E.O., Evans, W.D., and Owen, G.M.: A theoretical analysis of the accuracy of single-energy CT bone measurements. Phys. Med. Biol. 33(10), 1113 (1988).CrossRefGoogle Scholar
Hellmich, C., Kober, C., and Erdmann, B.: Micromechanics-based conversion of CT data. Ann. Biomed. Eng. 36(1), 108 (2008).Google Scholar
Radon, J.: Über die Bestimmung von Funktionen durch ihre Integralwere längs gewisser Mannigfaltigkeiten. [On the determination of functions from their integrals along certain manifolds]. SBLeipzig 29, 69, (1917).Google Scholar
Hounsfield, G.: A method of an apparatus for examination of a body by radiation such as x-ray or gamma-radiation. Patent specification 1283915, The Patent Office, 1972.Google Scholar
Medical Imaging and Technology Alliance (division of the National Electrical Manufacturers Association): DICOM PS3.3 2013-Information Object Definitions (2013).Google Scholar
Cobel, R. and Kingley, W.: Effect of porosity on physical properties of alumina. J. Am. Ceram. Soc. 39(11), 377 (1956).Google Scholar
Fritsch, A., Hellmich, C., and Young, P.: Micromechanics-derived scaling relations for poroelasticity and strength of brittle porous polycrystals. J. Appl. Mech. 80(2), 020905–1 (2013).Google Scholar
Fritsch, A., Dormieux, L., and Hellmich, C.: Porous polycrystals built up by uniformly and axisymmetrically oriented needles: Homogenization of elastic properties. C. R. Mec. 334(3), 151 (2006).CrossRefGoogle Scholar
Fritsch, A., Dormieux, L., Hellmich, C., and Sanahuja, J.: Mechanical behaviour of hydroxyapatite biomaterials: An experimentally validated micromechanical model for elasticity and strength. J. Biomed. Mater. Res. A 88(1), 149 (2009).Google Scholar
Sanahuja, J., Dormieux, L., Meille, S., Hellmich, C., and Fritsch, A.: Micromechanical explanation of elasticity and strength of gypsum: From elongated anisotropic crystals to isotropic porous polycrystals. J. Eng. Mech. 136(2), 239 (2010).Google Scholar
Fritsch, A., Hellmich, C., and Dormieux, L.: The role of disc-type crystal shape for micromechanical predictions of elasticity and strength of hydroxyapatite biomaterials. Philos. Trans. R. Soc., A 368(1917), 1913 (2010).Google Scholar
Ali, M. and Singh, B.: The effect of porosity on the properties of glass fibre-reinforced gypsum plaster. J. Mater. Sci. 10(11), 1920 (1975).Google Scholar
Phani, K.: Young’s modulus-porosity relation in gypsum systems. Am. Ceram. Soc. Bull. 65(12), 1584 (1986).Google Scholar
Tazawa, E.: Effect of self stress on flexural strength of gypsum-polymer composites. Adv. Cem. Based Mater. 7(1), 1 (1998).Google Scholar
Meille, S.: Etude du comportement mécanique du plâtre pris en relation avec sa microstructure [Study of the mechanical behaviour of gypsum with regard to its microstructure]. Ph.D. Thesis, INSA Lyon, Lyon, France (2001). (in French).Google Scholar
Colak, M.: Physical and mechanical properties of polymer-plaster composites. Mater. Lett. 60(16), 1977 (2006).Google Scholar
Craciun, F., Galassi, C., Roncari, E., Filippi, A., and Guidarelli, G.: Electro-elastic properties of porous piezoelectric ceramics obtained by tape casting. Ferroelectrics 205, 49 (1998).Google Scholar
Pabst, W., Gregorová, E., Tichá, G., and Týnová, E.: Effective elastic properties of alumina-zirconia composite ceramics. Part 4. Tensile modulus of porous alumina and zirconia. Ceram.-Silik. 48(4), 165 (2004).Google Scholar
Reynaud, C., Thévenot, F., Chartier, T., and Besson, J-L.: Mechanical properties and mechanical behaviour of SiC dense-porous laminates. J. Eur. Ceram. Soc. 25(5), 589 (2005).Google Scholar
Díaz, A. and Hampshire, S.: Characterisation of porous silicon nitride materials produced with starch. J. Eur. Ceram. Soc. 24(2), 413 (2004).Google Scholar
Pabst, W., Gregorová, E., and Tichá, G.: Elasticity of porous ceramics—A critical study of modulus-porosity relations. J. Eur. Ceram. Soc. 26(7), 1085 (2006).Google Scholar
Liang, L., Rulis, P., and Ching, W.Y.: Mechanical properties, electronic structure and bonding of α- and β-tricalcium phosphates with surface characterization. Acta Biomater. 6(9), 3763 (2010).Google Scholar
Mastrogiacomo, M., Komlev, V.S., Hausard, M., Peyrin, F., Turquier, F., Casari, S., Cedola, A., Rustichelli, F., and Cancedda, R.: Synchrotron radiation microtomography of bone engineered from bone marrow stromal cells. Tissue Eng. 10(11–12), 1767 (2004).Google Scholar
Komlev, V.S., Peyrin, F., Mastrogiacomo, M., Cedola, A., Papadimitropoulos, A., Rustichelli, F., and Cancedda, R.: Kinetics of in vivo bone deposition by bone marrow stromal cells into porous calcium phosphate scaffolds: An x-ray computed microtomography study. Tissue Eng. 12(12), 3449 (2006).Google Scholar
von Doernberg, M.C., von Rechenberg, B., Bohner, M., Grünenfelder, S., Harry van Lenthe, G., Müller, R., Gasser, B., Mathys, R., Baroud, G., and Auer, J.: In vivo behavior of calcium phosphate scaffolds with four different pore sizes. Biomaterials 27(30), 5186 (2006).CrossRefGoogle ScholarPubMed
Cedola, R., Guiliani, A., Komlev, A., Lagomarsino, V., Mastrogiacomo, S., Peyrin, M., Rustichelli, F., and Cancedda, F.: Bulk and interface investigations of scaffolds and tissue-engineered bones by x-ray microtomography and x-ray microdiffraction. Biomaterials 28(15), 2505 (2007).Google Scholar
Mastrogiacomo, M., Papadimitropoulos, A., Cedola, A., Peyrin, F., Giannoni, P., Pearce, S.G., Alini, M., Giannini, C., Guagliardi, A., and Cancedda, R.: Engineering of bone using bone marrow stromal cells and a silicon-stabilized tricalcium phosphate bioceramic: Evidence for a coupling between bone formation and scaffold resorption. Biomaterials 28(7), 1376 (2007).Google Scholar
Jones, A.C., Arns, C.H., Sheppard, A.P., Hutmacher, D.W., Milthorpe, B.K., and Knackstedt, M.A.: Assessment of bone ingrowth into porous biomaterials using MICRO-CT. Biomaterials 28(15), 2491 (2007).Google Scholar
Komlev, V.S., Mastrogiacomo, M., Pereira, R.C., Peyrin, F., Rustichelli, F., and Cancedda, R.: Biodegradation of porous calcium phosphate scaffolds in an ectopic bone formation model studied by x-ray computed microtomography. Eur. Cell Mater. 19, 136 (2010).Google Scholar
Lan Levengood, S.K., Polak, S.J., Poellmann, M.J., Hoelzle, D.J., Maki, A.J., Clark, S.G., Wheeler, M.B., and Wagoner Johnson, A.J.: The effect of BMP-2 on micro-and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity. Acta Biomater. 6(8), 3283 (2010).Google Scholar
Giuliani, A., Manescu, A., Langer, M., Rustichelli, F., Desiderio, V., Paino, F., De Rosa, A., Laino, L., d'Aquino, R., Tirino, V., and Papaccio, G.: Three years after transplants in human mandibles, histological and in-line holotomography revealed that stem cells regenerated a compact rather than a spongy bone: Biological and clinical implications. Stem Cells Transl. Med. 2(4), 316 (2013).Google Scholar
Rho, J.Y., Hobatho, M.C., and Ashman, R.B.: Relations of mechanical properties to density and CT numbers in human bone. Med. Eng. Phys. 17(5), 347 (1995).Google Scholar
Couteau, B., Hobatho, M.C., Darmana, R., Brignola, J.C., and Arlaud, J.Y.: Finite element modelling of the vibrational behaviour of the human femur using CT-based individualized geometrical and material properties. J. Biomech. 31(4), 383 (1998).Google Scholar
Keyak, J.H. and Falkinstein, Y.: Comparison of in situ and in vitro CT scan-based finite element model predictions of proximal femoral fracture load. Med. Eng. Phys. 25(9), 781 (2003).Google Scholar
Cong, A., Buijs, O.D., and Dragomir-Daescu, D.: In situ parameter identification of optimal density-elastic modulus relationships in subject-specific finite element models of the proximal femur. Med. Eng. Phys. 33(2), 164 (2011).Google Scholar
Hellmich, C., Ulm, F-J., and Dormieux, L.: Can the diverse elastic properties of trabecular and cortical bone be attributed to only a few tissue-independent phase properties and their interactions? Arguments from a multiscale approach. Biomech. Model. Mechanobiol. 2(4), 219 (2004).Google Scholar
Dejaco, A., Komlev, V.S., Jaroszewicz, J., Swieszkowski, W., and Hellmich, C.: Micro CT-based multiscale elasticity of double-porous (pre-cracked) hydroxyapatite granules for regenerative medicine. J. Biomech. 45(6), 1068 (2012).Google Scholar
Blanchard, R., Dejaco, A., Bongaers, E., and Hellmich, C.: Intravoxel bone micromechanics for microCT-based finite element simulations. J. Biomech. 46(15), 2710 (2013).Google Scholar
Fritsch, A., Hellmich, C., and Dormieux, L.: Ductile sliding between mineral crystals followed by rupture of collagen crosslinks: Experimentally supported micromechanical explanation of bone strength. J. Theor. Biol. 260(2), 230 (2009).Google Scholar
Eberhardsteiner, L., Hellmich, C., and Scheiner, S.: Layered water in crystal interfaces as source for bone viscoelasticity: Arguments from a multiscale approach. Comput. Methods Biomed. Eng. 17(1), 48 (2014).Google Scholar
Khanna, R., Katti, D., and Katti, K.: Nanomechanics of surface modified nanohydroxyapatite particulates used in biomaterials. J. Eng. Mech. 135(5), 468 (2009).Google Scholar
Khanna, R., Katti, D., and Katti, K.: AFM and nanoindentation studies of bone nodules on chitosan-polygalacturonic acid-hydroxyapatite nanocomposites. CMES 87(6), (2012).Google Scholar
Huang, S., Li, Z., Chen, Z., Chen, Q., and Pugno, N.: Study on the elastic-plastic behaviour of a porous hierarchical bioscaffold used for bone regeneration. Mater. Lett. 112(1), 43 (2013).Google Scholar
Chen, Q., Baino, F., Spriano, S., Pugno, N.M., and Vitale-Brovarone, C.: Modelling of the strength-porosity relationship in glass-ceramic foam scaffolds for bone repair. J. Eur. Ceram. Soc. 34(11), 2663 (2014).Google Scholar
Katz, E.P. and Li, S.T.: Structure and function of bone collagen fibrils. J. Mol. Biol. 80(1), 1 (1973).Google Scholar
Meek, K., Fullwood, N., Cooke, P., Elliott, G., Maurice, D., Quantock, A., Wall, R., and Worthington, C.: Synchrotron x-ray diffraction studies of the cornea, with implications for stromal hydration. Biophys. J. 60(2), 467 (1991).Google Scholar
Rougvie, M. and Bear, R.: An x-ray diffraction investigation of swelling by collagen. J. Am. Leather Chem. Assoc. 48(12), 735 (1953).Google Scholar
Morin, C., Hellmich, C., and Henits, P.: Fibrillar structure and elasticity of hydrating collagen: A quantitative multiscale approach. J. Theor. Biol. 317, 384 (2013).Google Scholar
Lees, S., Bonar, L.C., and Mook, H.A.: A study of dense mineralized tissue by neutron diffraction. Int. J. Biol. Macromol. 6(6), 321 (1984).CrossRefGoogle Scholar
Bonar, L.C., Lees, S., and Mook, H.A.: Neutron diffraction studies of collagen in fully mineralized bone. J. Mol. Biol. 181(2), 265 (1985).Google Scholar
Morin, C. and Hellmich, C.: Mineralization-driven bone tissue evolution follows from fluid-to-solid phase transformations in closed thermodynamic systems. J. Theor. Biol. 335(21), 185 (2013).Google Scholar
Azami, M., Samadikuchaksaraei, A., and Poursamar, S.A.: Synthesis and characterization of a laminated hydroxyapatite/gelatin nanocomposite scaffold with controlled pore structure for bone tissue engineering. Int. J. Artif. Organs 33(2), 86 (2010).Google Scholar
Lv, Q., Deng, M., Ulery, B., Nair, L., and Laurencin, C.: Nano-ceramic composite scaffolds for bioreactor-based bone engineering. Clin. Orthop. Relat. Res. 471(8), 2422 (2013).Google Scholar
Lv, Q., Nair, L., and Laurencin, C.: Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors. J. Biomed. Mater. Res. A 91(3), 679 (2008).Google Scholar
Cuy, J.L., Mann, A.B., Livi, K.J., Teaford, M.F., and Weihs, T.P.: Nanoindentation mapping of the mechanical properties of human molar tooth enamel. Arch. Oral Biol. 47(4), 281 (2002).Google Scholar
Miller, M., Bobko, C., Vandamme, M., and Ulm, F-J.: Surface roughness criteria for cement paste nanoindentation. Cem. Concr. Res. 38(4), 467 (2008).Google Scholar
Khanna, R., Katti, K.S., and Katti, D.R.: Nanomechanics of surface modified nanohydroxyapatite particulates used in biomaterials. J. Eng. Mech. 135(5), 468 (2009).Google Scholar
Malandrino, A., Fritsch, A., Lahayne, O., Kropik, K., Redl, H., Noailly, J., Lacroix, D., and Hellmich, C.: Anisotropic tissue elasticity in human lumbar vertebra, by means of a coupled ultrasound-micromechanics approach. Mater. Lett. 78(1), 154 (2012).Google Scholar
Peelen, J., Rejda, B., and de Groot, K.: Preparation and properties of sintered hydroxyapatite. Ceram. Int. 4(2), 71 (1978).Google Scholar
Shareef, M.Y., Messer, P.F., and van Noort, R.: Fabrication, characterization and fracture study of a machinable hydroxyapatite ceramic. Biomaterials 14(1), 69 (1993).Google Scholar
Martin, R.I. and Brown, P.W.: Mechanical properties of hydroxyapatite formed at physiological temperature. J. Mater. Sci.: Mater. Med. 6(3), 138 (1995).Google Scholar
Charriere, E., Terrazzoni, S., Pittet, C., Mordasini, P., Dutoit, M., Lemaıtre, J., and Zysset, P.: Mechanical characterization of brushite and hydroxyapatite cements. Biomaterials 22(21), 2937 (2001).Google Scholar
Akao, M., Aoki, H., and Kato, K.: Mechanical properties of sintered hydroxyapatite for prosthetic applications. J. Mater. Sci. 16(3), 809 (1981).Google Scholar
De With, G., van Dijk, H.J.A., Hattu, N., and Prijs, K.: Preparation, micro-structure and mechanical properties of dense polycrystalline hydroxyapatite. J. Mater. Sci. 16(6), 1592 (1981).Google Scholar
Liu, D-M.: Preparation and characterisation of porous hydroxyapatite bioceramic via a slip-casting route. Ceram. Int. 24(6), 441 (1998).Google Scholar
Arita, I.H., Wilkinson, D.S., Mondragon, M.A., and Castano, V.M.: Chemistry and sintering behaviour of thin hydroxyapatite ceramics with controlled porosity. Biomaterials 16(5), 403 (1995).Google Scholar
Luczynski, K.W., Dejaco, A., Lahayne, O., Jaroszewicz, J., Swieszkowski, W., and Hellmich, C.: MicroCT/micromechanics-based finite element models and quasi-static unloading tests deliver consistent values for Young's modulus of rapid-prototyped polymer-ceramic tissue engineering scaffold. Comput. Model. Eng. Sci. 87(6), 505 (2012).Google Scholar
Hara, T., Tanck, E., Homminga, J., and Huiskes, R.: The influence of microcomputed tomography threshold variations on the assessment of structural and mechanical trabecular bone properties. Bone 31(1), 107 (2002).CrossRefGoogle ScholarPubMed