The use of nanoindentation for characterizing the properties of mineralized hard tissues:​ state-of-the art review

Lewis, Gladius<sup>1</sup>; Nyman, Jeffry S.<sup>2</sup>

Affiliations

¹Department of Mechanical Engineering, The University of Memphis, Memphis, Tennessee 38152

²Vanderbilt Center for Bone Biology and Department of Orthopaedics and Rehabilitation, Vanderbilt University, Nashville, Tennessee 37232

Abstract and keywords

The use of nanoindentation to determine nanomechanical properties of mineralized tissues has been investigated extensively. A detailed, critical, and comprehensive review of this literature is the subject of the present work. After stating the motivation for the review, a succinct presentation of the challenges, advantages, and disadvantages of the various quasi-static nanoindentation test methods (to obtain elastic modulus, E, and hardness, H) and dynamic test methods (to obtain storage and loss moduli and/or loss/damping factor) is given in the form of a primer. Explicative summaries of literature reports on various intrinsic and extrinsic factors that significantly influence E and H, followed by 15 suggested topics for future research, are included additionally. This review is designed to present a compact guide to the principles of the nanoindentation technique and to emphasize considerations when determining material properties of mineralized tissues.

Keywords: nanoindentation; bone; teeth; stiffness; hardness

Links

DOI: 10.1002/jbm.b.31092

PubMed: 18395829

WoS: 000259328900035

History

Received: 2007-08-02

Revised: 2008-01-20

Accepted: 2008-01-25

Online: 2008-04-07

Cited Works (25)

Year	Entry
2005	Busa B, Miller LM, Rubin CT, Qin Y-X, Judex S. Rapid establishment of chemical and mechanical properties during lamellar bone formation. Calcif Tiss Int. December 2005;77(6):386-394.
1999	Roy ME, Rho J-Y, Tsui TY, Evans ND, Pharr GM. Mechanical and morphological variation of the human lumbar vertebral cortical and trabecular bone. J Biomed Mater Res. February 1999;A44(2):191-197.
2006	Donnelly E, Williams RM, Downs SA, Dickinson ME, Baker SP, van der Meulen MCH. Quasistatic and dynamic nanomechanical properties of cancellous bone tissue relate to collagen content and organization. J Mater Res. August 2006;21(8):2106-2117.
2007	Tai K, Dao M, Suresh S, Palazoglu A, Ortiz C. Nanoscale heterogeneity promotes energy dissipation in bone. Nat Mater. June 2007;6(6):454-462.
2002	Fan Z, Swadener JG, Rho JY, Roy ME, Pharr GM. Anisotropic properties of human tibial cortical bone as measured by nanoindentation. J Orthop Res. July 2002;20(4):806-810.
2003	Fan Z, Rho J-Y. Effects of viscoelasticity and time-dependent plasticity on nanoindentation measurements of human cortical bone. J Biomed Mater Res. October 1, 2003;A67(1):208-214.
2007	Miller LM, Little W, Schirmer A, Sheik F, Busa B, Judex S. Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res. July 2007;22(7):1037-1045.
2001	Rho JY, Currey JD, Zioupos P, Pharr GM. The anisotropic Young's modulus of equine secondary osteones and interstitial bone determined by nanoindentation. J Exp Biol. May 2001;204(10):1775-1781.
2004	Li X, Chang W-C, Chao YJ, Wang R, Chang M. Nanoscale structural and mechanical characterization of a natural nanocomposite material: the shell of red abalone. Nano Lett. 2004;4(4):613-617.
1977	Carter DR, Hayes WC. The compressive behavior of bone as a two-phase porous structure. J Bone Joint Surg. 1977;59A(7):954-962.
2005	Hoffler CE, Guo XE, Zysset PK, Goldstein SA. An application of nanoindentation technique to measure bone tissue lamellae properties. J Biomech Eng. January 2005;127(7):1046-1053.
2005	Tai K, Qi HJ, Ortiz C. Effect of mineral content on the nanoindentation properties and nanoscale deformation mechanisms of bovine tibial cortical bone. J Mater Sci Mater Med. October 2005;16(10):947-959.
1992	Oliver WC, Pharr GM. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res. 1992;7(6):1564-1583.
2006	Ebenstein DM, Pruitt LA. Nanoindentation of biological materials. Nano Today. August 2006;1(3):26-33.
2001	Hengsberger S, Kulik A, Zysset P. A combined atomic force microscopy and nanoindentation technique to investigate the elastic properties of bone structural units. Eur Cell Mater. January–June 2001;1:12-17.
2002	Hengsberger S, Kulik A, Zysset P. Nanoindentation discriminates the elastic properties of individual human bone lamellae under dry and physiological conditions. Bone. 2002;30(1):178-184.
2006	Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, Kinney JH, Bonewald LF. Glucocorticoid‐treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo‐treated or estrogen‐deficient mice. J Bone Miner Res. March 2006;21(3):466-476.
2004	Silva MJ, Brodt MD, Fan Z, Rho J-Y. Nanoindentation and whole-bone bending estimates of material properties in bones from the senescence accelerated mouse SAMP6. J Biomech. November 2004;37(11):1639-1646.
2007	Mulder L, Koolstra JH, den Toonder JMJ, van Eijden TMGJ. Intratrabecular distribution of tissue stiffness and mineralization in developing trabecular bone. Bone. August 2007;41(2):256-265.
2006	Donnelly E, Baker SP, Boskey AL, van der Meulen MC. Effects of surface roughness and maximum load on the mechanical properties of cancellous bone measured by nanoindentation. J Biomed Mater Res. May 2006;A77(2):426-435.
2006	Mittra E, Akella S, Qin Y-X. The effects of embedding material, loading rate and magnitude, and penetration depth in nanoindentation of trabecular bone. J Biomed Mater Res. October 2006;A79(1):86-93.
2004	Oliver WC, Pharr GM. Measurement of hardness and elastic modulus by instrumented indentation: advances in understanding and refinements to methodology. J Mater Res. January 2004;19(1):3-20.
2003	Xu J, Rho JY, Mishra SR, Fan Z. Atomic force microscopy and nanoindentation characterization of human lamellar bone prepared by microtome sectioning and mechanical polishing technique. J Biomed Mater Res. December 1, 2003;A67(3):719-726.
2004	Bushby AJ, Ferguson VL, Boyde A. Nanoindentation of bone: comparison of specimens tested in liquid and embedded in polymethylmethacrylate. J Bone Miner Res. January 2004;19(1):249-259.
1999	Rho J-Y, Roy ME II, Tsui TY, Pharr GM. Elastic properties of microstructural components of human bone tissue as measured by nanoindentation. J Biomed Mater Res. 1999;A45(1):48-54.

Cited By (44)

Year	Entry
2018	Wu D, Isaksson P, Ferguson SJ, Persson C. Young’s modulus of trabecular bone at the tissue level: a review. Acta Biomater. September 15, 2018;78:1.
2021	Casari D, Michler J, Zysset P, Schwiedrzik J. Microtensile properties and failure mechanisms of cortical bone at the lamellar level. Acta Biomater. January 15, 2021;120:135-145.
2010	Wolfram U, Wilke H-J, Zysset PK. Rehydration of vertebral trabecular bone: influences on its anisotropy, its stiffness and the indentation work with a view to age, gender and vertebral level. Bone. February 2010;46(2):348-354.
2010	Isaksson H, Malkiewicz M, Nowak R, Helminen HJ, Jurvelin JS. Rabbit cortical bone tissue increases its elastic stiffness but becomes less viscoelastic with age. Bone. December 2010;47(6):1030-1038.
2016	Mirzaali MJ, Schwiedrzik JJ, Thaiwichai S, Best JP, Michler J, Zysset PK, Wolfram U. Mechanical properties of cortical bone and their relationships with age, gender, composition and microindentation properties in the elderly. Bone. December 2016;93:196-211.
2021	Vahidi G, Rux C, Sherk VD, Heveran CM. Lacunar-canalicular bone remodeling: impacts on bone quality and tools for assessment. Bone. February 2021;143:115663.
2020	Maghsoudi-Ganjeh M, Wang X, Zeng X. Nanomechanics and ultrastructure of bone: a review. Comput Model Eng Sci. 2020;125(1):1-32.
2019	Semaan M, Karam E, Baron C, Pithioux M. Estimation of the elastic modulus of child cortical bone specimens via microindentation. Connect Tissue Res. July 4, 2019;60(4):399-405.
2010	Wolfram U, Wilke H-J, Zysset PK. Valid μ finite element models of vertebral trabecular bone can be obtained using tissue properties measured with nanoindentation under wet conditions. J Biomech. 2010;43(9):1731-1737.
2010	Isaksson H, Nagao S, MaŁkiewicz M, Julkunen P, Nowak R, Jurvelin JS. Precision of nanoindentation protocols for measurement of viscoelasticity in cortical and trabecular bone. J Biomech. 2010;43(12):2410-2417.
2011	Carnelli D, Lucchini R, Ponzoni M, Contro R, Vena P. Nanoindentation testing and finite element simulations of cortical bone allowing for anisotropic elastic and inelastic mechanical response. J Biomech. July 7, 2011;44(10):1852-1858.
2012	Feng L, Chittenden M, Schirer J, Dickinson M, Jasiuk I. Mechanical properties of porcine femoral cortical bone measured by nanoindentation. J Biomech. June 26, 2012;45(10):1775-1782.
2014	Lambers FM, Bouman AR, Tkachenko EV, Keaveny TM, Hernandez CJ. The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone. J Biomech. November 28, 2014;47(15):3605-3612.
2010	Carnelli D, Gastaldi D, Sassi V, Contro R, Ortiz C, Vena P. A finite element model for direction-dependent mechanical response to nanoindentation of cortical bone allowing for anisotropic post-yield behavior of the tissue. J Biomech Eng. August 2010;132(8):081008.
2019	Grover K, Hu M, Lin L, Muir J, Qin Y-X. Functional disuse initiates medullary endosteal micro-architectural impairment in cortical bone characterized by nanoindentation. J Bone Min Metab. November 2019;37(6):1048-1057.
2011	Pathak S, Swadener JG, Kalidindi SR, Courtland H-W, Jepsen KJ, Goldman HM. Measuring the dynamic mechanical response of hydrated mouse bone by nanoindentation. J Mech Behav Biomed Mater. January 2011;4(1):34-43.
2012	Spiesz EM, Roschger P, Zysset PK. Elastic anisotropy of uniaxial mineralized collagen fibers measured using two-directional indentation: effects of hydration state and indentation depth. J Mech Behav Biomed Mater. August 2012;12:20-28.
2012	Pathak S, Vachhani SJ, Jepsen KJ, Goldman HM, Kalidindi SR. Assessment of lamellar level properties in mouse bone utilizing a novel spherical nanoindentation data analysis method. J Mech Behav Biomed Mater. September 2012;13:102-117.
2013	Carretta R, Luisier B, Bernoulli D, Stüssi E, Müller R, Lorenzetti S. Novel method to analyze post-yield mechanical properties at trabecular bone tissue level. J Mech Behav Biomed Mater. 2013;20:6-18.
2013	Carretta R, Stüssi E, Müller R, Lorenzetti S. Within subject heterogeneity in tissue-level post-yield mechanical and material properties in human trabecular bone. J Mech Behav Biomed Mater. August 2013;24:64-73.
2020	Nedelkovski V, Hahn R, Mayrhofer PH, Steiger-Thirsfeld A, Bernardi J, Thurner PJ. Influence of experimental constraints on micromechanical assessment of micromachined hard-tissue samples. J Mech Behav Biomed Mater. June 2020;106:103741.
2015	Chittenden M, Najafi AR, Li J, Jasiuk I. Nanoindentation and ash content study of age dependent changes in porcine cortical bone. J Mech Med Biol. October 2015;15(5):1550074.
2011	Lorenzetti S, Carretta R, Müller R, Stüssi E. A new device and method for measuring the elastic modulus of single trabeculae. Med Eng Phys. October 2011;33(8):993-1000.
2014	Schwiedrzik J, Raghavan R, Bürki A, LeNader V, Wolfram U, Michler J, Zysset P. In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone. Nat Med. July 2014;13(7):740-747.
2021	Shipov A, Zaslansky P, Riesemeier H, Segev G, Atkins A, Kalish-Achrai N, Weiner S, Shahar R. The influence of estrogen deficiency on the structural and mechanical properties of rat cortical bone. PeerJ. January 13, 2021;9:e10213.
2018	Guss JD. The Role of the Gut Microbiome in Bone and Joint [PhD thesis]. Ithaca, NY: Cornell University; December 2018.
2012	Sharma D. Effects of Estrogen Deficiency on the Osteocyte Lacunar-Canalicular Network [PhD thesis]. New York, NY: The City University of New York; 2012.
2014	Carretta R. Post-Yield Mechanics and Material Composition of Single Trabeculae: A Combined Experimental and Modelling Approach [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2014.
2010	Feng L. Multi-Scale Characterization of Swine Femoral Cortical Bone and Long Bone Defect Repair by Regeneration [PhD thesis]. University of Illinois at Urbana-Champaign; 2010.
2015	Rodriguez-Florez N. Mechanics of Cortical Bone: Exploring the Micro- and Nano-Scale [PhD thesis]. Imperial College London; January 2015.
2014	Jameson JR. Characterization of Bone Material Properties and Microstructure in Osteogenesis Imperfecta/brittle Bone Disease [PhD thesis]. Marquette University; December 2014.
2020	Karali A. Multi-Scale Evaluation of Bone Combining Indentation, in Situ XCT Mechanics and Digital Volume Correlation [PhD thesis]. Portsmouth, England: University of Portsmouth; 2020.
2012	Jimenez Palomar I. Mechanical Properties of Bone At the Sub-lamellar Level [PhD thesis]. London, England: Queen Mary University of London; September 2012.
2012	Acerbo AS. Local Chemical and Nanostructural Properties of Rat Cortical Bone Are Altered by Osteoporosis and Pharmaceutical Treatments [PhD thesis]. Stony Brook, NY: Stony Brook University; August 2012.
2015	Grover K. Osteopenia Uncovered by Remodeling in Spatial Distribution of Elastic Moduli in Orthogonal Orientations: A Nanoindentation Study [Master's thesis]. Stony Brook, NY: Stony Brook University; May 2015.
2020	Stipsitz M. Development of a Nonlinear Micro Finite Element Framework for Image-Based Simulations in Bone Biomechanics [PhD thesis]. Vienna University of Technology; 2020.
2020	Plett RM. Enhanced Longitudinal Analysis of Bone Strength Estimated by 3D Bone Imaging and the Finite Element Method [Master's thesis]. Calgary, AB: University of Calgary; October 2020.
2016	Zhang Z. On the Fatigue Crack Growth Resistance of Resin-Dentin Bonded Interfaces: Aging, Microstructure and Durability [PhD thesis]. Baltimore County, University of Maryland; 2016.
2011	Raghavan M. Investigation of Mineral and Collagen Organization in Bone Using Raman Spectroscopy [PhD thesis]. University of Michigan; 2011.
2014	Schwiedrzik JJ. Experimental, Theoretical and Numerical Investigation of the Nonlinear Micromechanical Properties of Bone [PhD thesis]. Universität Bern; 2014.
2011	Wolfram U. Mechanical Multiscale Characterisation of Vertebral Trabecular Bone for the Prediction of Vertebral Fracture Risk [PhD thesis]. University of Ulm; 2011.
2018	Burke MV. Quantification of Changes in Vertebral Bone Quality in the Presence of Metastases [PhD thesis]. University of Toronto; 2018.
2013	Faingold A. Bone Elementary Units: Mechanical Properties and Structure [PhD thesis]. Weizmann Institute of Science; February 2013.
2011	Vivanco Morales JF. Investigation of Fabrication and Environmental Effects on Bioceramic Bone Scaffolds [PhD thesis]. University of Wisconsin – Madison; 2011.