Skip to main content

Advances and Applications of Nanomechanical Tools in Cartilage Tissue Engineering

  • Chapter
  • First Online:
A Tissue Regeneration Approach to Bone and Cartilage Repair

Part of the book series: Mechanical Engineering Series ((MES))

  • 1641 Accesses

Abstract

Native articular cartilage is a hydrated macromolecular composite with heterogeneous composition, structure, and mechanical properties at a hierarchy of length scales. Recently, with the advances of nanotechnology, nanomechanical tools have shown great promises in understanding the mechanistic origins of cartilage function and improving the design of tissue repair strategies. This chapter reviews the current state-of-the-art nanomechanical tools, with a special focus on atomic force microscopy (AFM)-based methods. With the aid of these tools, ultrastructure of individual molecules and spatially variant mechanical properties of tissue engineered products can be directly quantified. Novel scientific information was derived from recent studies via the nanomechanical methods, including choice of cell sources, cell differentiation and purification, as well as biochemical and biomechanical stimulations. It is hoped that further progress in nanomechanical techniques and their applications on engineered cartilage could provide molecular-level mechanistic insight necessary to improve current tissue engineering strategies and propel them toward a functional repair of damaged cartilage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alexopoulos LG, Haider MA, Vail TP, Guilak F (2003) Alterations in the mechanical properties of the human chondrocyte pericellular matrix with osteoarthritis. J Biomech Eng 125(3):323–333. doi:10.1115/1.1579047

    Google Scholar 

  • Barbero A, Grogan S, Schäfer D, Heberer M, Mainil-Varlet P, Martin I (2004) Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity. Osteoarthritis Cartilage 12(6):476–484. doi:10.1016/j.joca.2004.02.010

    Google Scholar 

  • Barbour KE, Helmick CG, Theis KA, Murphy LB, Hootman JM, Brady TJ, Cheng YJ (2013) Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation—United States, 2010–2012. Morb Mortal Wkly Rep 62(44):869–873

    Google Scholar 

  • Benz M, Chen N, Israelachvili J (2004) Lubrication and wear properties of grafted polyelectrolytes, hyaluronan and hylan, measured in the surface forces apparatus. J Biomed Mater Res A 71A(1):6–15. doi:10.1002/jbm.a.30123

    Google Scholar 

  • Binnig G, Quate CF, Gerber C (1986) Atomic force microscope. Phys Rev Lett 56(9):930–933. doi:10.1103/PhysRevLett.56.930

    Google Scholar 

  • Blin G, Nury D, Stefanovic S, Neri T, Guillevic O, Brinon B, Bellamy V, Rüecker-Martin C, Barbry P, Bel A, Bruneval P, Cowan C, Pouly J, Mitalipov S, Gouadon E, Binder P, Hagège A, Desnos M, Renaud JF, Menasché P, Pucéat M (2010) A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J Clin Invest 120(4):1125–1139. doi:10.1172/jci40120

    Google Scholar 

  • Bolton MC, Dudhia J, Bayliss MT (1999) Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability. Biochem J 337(1):77–82. doi:10.1042/0264-6021:3370077

    Google Scholar 

  • Brown MP, Trumble TN, Sandy JD, Merritt KA (2007) A simplified method of determining synovial fluid chondroitin sulfate chain length. Osteoarthritis Cartilage 15(12):1443–1445. doi:10.1016/j.joca.2007.05.018

    Google Scholar 

  • Buckwalter JA, Rosenberg LC, Tang L-H (1984) The effect of link protein on proteoglycan aggregate structure—an electron microscopic study of the molecular architecture and dimensions of proteoglycan aggregates reassembled from the proteoglycan monomers and link proteins of bovine fetal epiphyseal cartilage. J Biol Chem 259(9):5361–5363

    Google Scholar 

  • Buschmann MD, Grodzinsky AJ (1995) A molecular model of proteoglycan-associated electrostatic forces in cartilage mechanics. J Biomech Eng 117(2):179–192. doi:10.1115/1.2796000

    Google Scholar 

  • Buschmann MD, Kim Y-J, Wong M, Frank E, Hunziker EB, Grodzinsky AJ (1999) Stimulation of aggrecan synthesis in cartilage explants by cyclic loading is localized to regions of high interstitial fluid flow. Arch Biochem Biophys 366(1):1–7. doi:10.1006/abbi.1999.1197

    Google Scholar 

  • Calabro A, Midura RJ, Wang A, West L, Plaas A, Hascall VC (2001) Fluorophore-assisted carbohydrate electrophoresis (FACE) of glycosaminoglycans. Osteoarthritis Cartilage 9(S1):S16–S22. doi:10.1053/joca.2001.0439

    Google Scholar 

  • Carpick RW, Ogletree DF, Salmeron M (1999) A general equation for fitting contact area and friction vs load measurements. J Colloid Interface Sci 211(2):395–400. doi:10.1006/jcis.1998.6027

    Google Scholar 

  • Chan SMT, Neu CP, DuRaine G, Komvopoulos K, Reddi AH (2010) Atomic force microscope investigation of the boundary-lubricant layer in articular cartilage. Osteoarthritis Cartilage 18(7):956–963. doi:10.1016/j.joca.2010.03.012

    Google Scholar 

  • Chang DP, Abu-Lail NI, Coles JM, Guilak F, Jay GD, Zauscher S (2009) Friction force microscopy of lubricin and hyaluronic acid between hydrophobic and hydrophilic surfaces. Soft Matter 5(18):3438–3445. doi:10.1039/b907155e

    Google Scholar 

  • Chang DP, Abu-Lail NI, Guilak F, Jay GD, Zauscher S (2008) Conformational mechanics, adsorption, and normal force interactions of lubricin and hyaluronic acid on model surfaces. Langmuir 24(4):1183–1193. doi:10.1021/la702366t

    Google Scholar 

  • Chang DP, Guilak F, Jay GD, Zauscher S (2014) Interaction of lubricin with type II collagen surfaces: adsorption, friction, and normal forces. J Biomech 47(3):659–666. doi:10.1016/j.jbiomech.2013.11.048

    Google Scholar 

  • Chang J, Poole CA (1997) Confocal analysis of the molecular heterogeneity in the pericellular microenvironment produced by adult canine chondrocytes cultured in agarose gel. Histochem J 29(7):515–528. doi:10.1023/a:1026467724216

    Google Scholar 

  • Chen C-H, Yeh M-L, Geyer M, Wang G-J, Huang M-H, Heggeness MH, Höök M, Luo Z-P (2006) Interactions between collagen IX and biglycan measured by atomic force microscopy. Biochem Biophys Res Commun 339(1):204–208. doi:10.1016/j.bbrc.2005.10.205

    Google Scholar 

  • Coles JM, Zhang L, Blum JJ, Warman ML, Jay GD, Guilak F, Zauscher S (2010) Loss of cartilage structure, stiffness, and frictional properties in mice lacking PRG4. Arthritis Rheum 62(6):1666–1674. doi:10.1002/art.27436

    Google Scholar 

  • Connelly JT, Wilson CG, Levenston ME (2008) Characterization of proteoglycan production and processing by chondrocytes and BMSCs in tissue engineered constructs. Osteoarthritis Cartilage 16(9):1092–1100. doi:10.1016/j.joca.2008.01.004

    Google Scholar 

  • Darling EM, Topel M, Zauscher S, Vail TP, Guilak F (2008) Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. J Biomech 41(2):454–464. doi:10.1016/j.jbiomech.2007.06.019

    Google Scholar 

  • Darling EM, Wilusz RE, Bolognesi MP, Zauscher S, Guilak F (2010) Spatial mapping of the biomechanical properties of the pericellular matrix of articular cartilage measured in situ via atomic force microscopy. Biophys J 98(12):2848–2856. doi:10.1016/j.bpj.2010.03.037

    Google Scholar 

  • Darling EM, Zauscher S, Guilak F (2006) Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy. Osteoarthritis Cartilage 14(6):571–579. doi:10.1016/j.joca.2005.12.003

    Google Scholar 

  • Dean D, Han L, Grodzinsky AJ, Ortiz C (2006) Compressive nanomechanics of opposing aggrecan macromolecules. J Biomech 39(14):2555–2565. doi:10.1016/j.jbiomech.2005.09.007

    Google Scholar 

  • Dean D, Han L, Ortiz C, Grodzinsky AJ (2005) Nanoscale conformation and compressibility of cartilage aggrecan using microcontact printing and atomic force microscopy. Macromolecules 38(10):4047–4049. doi:10.1021/ma047626k

    Google Scholar 

  • Dean D, Seog J, Ortiz C, Grodzinsky AJ (2003) Molecular-level theoretical model for electrostatic interactions within polyelectrolyte brushes: applications to charged glycosaminoglycans. Langmuir 19(13):5526–5539. doi:10.1021/la027001k

    Google Scholar 

  • Desrochers J, Amrein MA, Matyas JR (2010) Structural and functional changes of the articular surface in a post-traumatic model of early osteoarthritis measured by atomic force microscopy. J Biomech 43(16):3091–3098. doi:10.1016/j.jbiomech.2010.08.009

    Google Scholar 

  • Dexheimer V, Mueller S, Braatz F, Richter W (2011) Reduced reactivation from dormancy but maintained lineage choice of human mesenchymal stem cells with donor age. PLoS One 6(8):e22980. doi:10.1371/journal.pone.0022980

    Google Scholar 

  • Diekman BO, Christoforou N, Willard VP, Sun H, Sanchez-Adams J, Leong KW, Guilak F (2012) Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells. Proc Natl Acad Sci USA 109(47):19172–19177. doi:10.1073/pnas.1210422109

    Google Scholar 

  • Dimitriadis EK, Horkay F, Maresca J, Kachar B, Chadwick RS (2002) Determination of elastic moduli of thin layers of soft material using the atomic force microscope. Biophys J 82(5):2798–2810. doi:10.1016/S0006-3495(02)75620-8

    Google Scholar 

  • Docheva D, Padula D, Popov C, Mutschler W, Clausen-Schaumann H, Schieker M (2008) Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy. J Cell Mol Med 12(2):537–552. doi:10.1111/j.1582-4934.2007.00138.x

    Google Scholar 

  • Donnan FG (1911) Theorie der membrangleichgewichte und membranpotentiale bei vorhandensein von nicht dialysierenden elektrolyten. Ein beitrag zur physikalisch-chemischen physiologie. Zeitschrift für Electrochemie 17(14):572–581. doi:10.1002/bbpc.19110171405

  • Ebenstein DM, Kuo A, Rodrigo JJ, Reddi AH, Ries M, Pruitt L (2004) A nanoindentation technique for functional evaluation of cartilage repair tissue. J Mater Res 19(1):273–281. doi:10.1557/jmr.2004.19.1.273

    Google Scholar 

  • Ebenstein DM, Pruitt LA (2004) Nanoindentation of soft hydrated materials for application to vascular tissues. J Biomed Mater Res A 69A(2):222–232

    Google Scholar 

  • Eyre DR, Apon S, Wu J-J, Ericsson LH, Walsh KA (1987) Collagen type IX: evidence for covalent linkages to type II collagen in cartilage. FEBS Lett 220(2):337–341. doi:10.1016/0014-5793(87)80842-6

    Google Scholar 

  • Farndale RW, Buttle DJ, Barrett AJ (1986) Improved quantitation and discrimination of sulfated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 883(2):173–177. doi:10.1016/0304-4165(86)90306-5

    Google Scholar 

  • Felka T, Schäfer R, Schewe B, Benz K, Aicher WK (2009) Hypoxia reduces the inhibitory effect of IL-1β on chondrogenic differentiation of FCS-free expanded MSC. Osteoarthritis Cartilage 17(10):1368–1376. doi:10.1016/j.joca.2009.04.023

    Google Scholar 

  • Fitzgerald JB, Jin M, Dean D, Wood DJ, Zheng MH, Grodzinsky AJ (2004) Mechanical compression of cartilage explants induces multiple time-dependent gene expression patterns and involves intracellular calcium and cyclic AMP. J Biol Chem 279(19):19502–19511. doi:10.1074/jbc.M400437200

    Google Scholar 

  • Flechtenmacher J, Huch K, Thonar E, Mollenhauer JA, Davies SR, Schmid TM, Puhl W, Sampath TK, Aydelotte MB, Kuettner KE (1996) Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes. Arthritis Rheum 39(11):1896–1904. doi:10.1002/art.1780391117

    Google Scholar 

  • Francioli S, Cavallo C, Grigolo B, Martin I, Barbero A (2011) Engineered cartilage maturation regulates cytokine production and interleukin-1 beta response. Clin Orthop Relat Res 469(10):2773–2784. doi:10.1007/s11999-011-1826-x

    Google Scholar 

  • Franke O, Durst K, Maier V, Göken M, Birkholz T, Schneider H, Hennig F, Gelse K (2007) Mechanical properties of hyaline and repair cartilage studied by nanoindentation. Acta Biomater 3(6):873–881. doi:10.1016/j.actbio.2007.04.005

    Google Scholar 

  • Freed LE, Vunjak-Novakovic G (1995) Cultivation of cell-polymer tissue constructs in simulated microgravity. Biotechnol Bioeng 46(4):306–313. doi:10.1002/bit.260460403

    Google Scholar 

  • Grad S, Loparic M, Peter R, Stolz M, Aebi U, Alini M (2012) Sliding motion modulates stiffness and friction coefficient at the surface of tissue engineered cartilage. Osteoarthritis Cartilage 20(4):288–295. doi:10.1016/j.joca.2011.12.010

    Google Scholar 

  • Graff RD, Kelley SS, Lee GM (2003) Role of pericellular matrix in development of a mechanically functional neocartilage. Biotechnol Bioeng 82(4):457–464. doi:10.1002/bit.10593

    Google Scholar 

  • Guilak F (2000) The deformation behavior and viscoelastic properties of chondrocytes in articular cartilage. Biorheology 37(1–2):27–44

    Google Scholar 

  • Guilak F, Butler DL, Goldstein SA (2001) Functional tissue engineering: the role of biomechanics in articular cartilage repair. Clin Orthop Relat Res 391:S295–S305

    Google Scholar 

  • Guilak F, Estes BT, Diekman BO, Moutos FT, Gimble JM (2010) 2010 Nicolas Andry award: multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering. Clin Orthop Relat Res 468(9):2530–2540. doi:10.1007/s11999-010-1410-9

    Google Scholar 

  • Guilak F, Jones WR, Ting-Beall HP, Lee GM (1999) The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage 7(1):59–70. doi:10.1053/joca.1998.0162

    Google Scholar 

  • Guilak F, Ratcliffe A, Lane N, Rosenwasser MP, Mow VC (1994) Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis. J Orthop Res 12(4):474–484. doi:10.1002/jor.1100120404

    Google Scholar 

  • Gupta HS, Schratter S, Tesch W, Roschger P, Berzlanovich A, Schoeberl T, Klaushofer K, Fratzl P (2005) Two different correlations between nanoindentation modulus and mineral content in the bone-cartilage interface. J Struct Biol 149(2):138–148. doi:10.1016/j.jsb.2004.10.010

    Google Scholar 

  • Han L, Dean D, Daher LA, Grodzinsky AJ, Ortiz C (2008) Cartilage aggrecan can undergo self-adhesion. Biophys J 95(10):4862–4870. doi:10.1529/biophysj.107.128389

    Google Scholar 

  • Han L, Dean D, Mao P, Ortiz C, Grodzinsky AJ (2007a) Nanoscale shear deformation mechanisms of opposing cartilage aggrecan macromolecules. Biophys J 93(5):L23–L25. doi:10.1529/biophysj.107.114025

    Google Scholar 

  • Han L, Dean D, Ortiz C, Grodzinsky AJ (2007b) Lateral nanomechanics of cartilage aggrecan macromolecules. Biophys J 92(4):1384–1398. doi:10.1529/biophysj.106.091397

    Google Scholar 

  • Han L, Frank EH, Greene JJ, Lee H-Y, Hung H-HK, Grodzinsky AJ, Ortiz C (2011a) Time-dependent nanomechanics of cartilage. Biophys J 100(7):1846–1854. doi:10.1016/j.bpj.2011.02.031

    Google Scholar 

  • Han L, Grodzinsky AJ, Ortiz C (2011b) Nanomechanics of the cartilage extracellular matrix. Annu Rev Mater Res 41:133–168. doi:10.1146/annurev-matsci-062910-100431

    Google Scholar 

  • Harder A, Walhorn V, Dierks T, Fernàndez-Busquets X, Anselmetti D (2010) Single-molecule force spectroscopy of cartilage aggrecan self-adhesion. Biophys J 99(10):3498–3504. doi:10.1016/j.bpj.2010.09.002

    Google Scholar 

  • Hardingham TE, Fosang AJ (1992) Proteoglycans: many forms and many functions. FASEB J 6(3):861–870. doi:10.1096/fj.1530-6860

    Google Scholar 

  • Hardingham TE, Muir H (1972) The specific interaction of hyaluronic acid with cartilage proteoglycans. Biochim Biophys Acta 279(2):401–405. doi:10.1016/0304-4165(72)90160-2

    Google Scholar 

  • Hedlund H, Hedbom E, HeinegÃ¥rd D, Mengarelli-Widholm S, Reinholt FP, Svensson O (1999) Association of the aggrecan keratan sulfate-rich region with collagen in bovine articular cartilage. J Biol Chem 274(9):5777–5781. doi:10.1074/jbc.274.9.5777

    Google Scholar 

  • HeinegÃ¥rd D (2009) Proteoglycans and more - from molecules to biology. Int J Exp Pathol 90(6):575–586. doi:10.1111/j.1365-2613.2009.00695.x

    Google Scholar 

  • Hertz H (1882) Ãœber die Berührung fester elastischer Körper. J Reine Angew Math 92:156–171

    MATH  Google Scholar 

  • Hollander AP, Heathfield TF, Webber C, Iwata Y, Bourne R, Rorabeck C, Poole AR (1994) Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. J Clin Invest 93(4):1722–1732. doi:10.1172/jci117156

    Google Scholar 

  • Huey DJ, Hu JC, Athanasiou KA (2012) Unlike bone, cartilage regeneration remains elusive. Science 338(6109):917–921. doi:10.1126/science.1222454

    Google Scholar 

  • Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10(6):432–463. doi:10.1053/joca.2002.0801

    Google Scholar 

  • Hunziker EB, Kapfinger E, Geiss J (2007) The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthritis Cartilage 15(4):403–413. doi:10.1016/j.joca.2006.09.010

    Google Scholar 

  • Im G-I, Jung N-H, Tae S-K (2006) Chondrogenic differentiation of mesenchymal stem cells isolated from patients in late adulthood: the optimal conditions of growth factors. Tissue Eng 12(3):527–536. doi:10.1089/ten.2006.12.527

    Google Scholar 

  • Israel MA, Yuan SH, Bardy C, Reyna SM, Mu YL, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, Carson CT, Laurent LC, Marsala M, Gage FH, Remes AM, Koo EH, Goldstein LSB (2012) Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482(7384):216–220. doi:10.1038/nature10821

    Google Scholar 

  • Jay GD (2004) Lubricin and surfacing of articular joints. Curr Opin Orthop 15(5):355–359

    Google Scholar 

  • Jay GD, Britt DE, Cha CJ (2000) Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. J Rheumatol 27(3):594–600

    Google Scholar 

  • Jay GD, Torres JR, Warman ML, Laderer MC, Breuer KS (2007) The role of lubricin in the mechanical behavior of synovial fluid. Proc Natl Acad Sci USA 104(15):6194–6199. doi:10.1073/pnas.0608558104

    Google Scholar 

  • Jiang Y, Mishima H, Sakai S, Liu Y-K, Ohyabu Y, Uemura T (2008) Gene expression analysis of major lineage-defining factors in human bone marrow cells: effect of aging, gender, and age-related disorders. J Orthop Res 26(7):910–917. doi:10.1002/jor.20623

    Google Scholar 

  • Jones ARC, Gleghorn JP, Hughes CE, Fitz LJ, Zollner R, Wainwright SD, Caterson B, Morris EA, Bonassar LJ, Flannery CR (2007) Binding and localization of recombinant lubricin to articular cartilage surfaces. J Orthop Res 25(3):283–292. doi:10.1002/jor.20325

    Google Scholar 

  • June RK, Ly S, Fyhrie DP (2009) Cartilage stress-relaxation proceeds slower at higher compressive strains. Arch Biochem Biophys 483(1):75–80. doi:10.1016/j.abb.2008.11.029

    Google Scholar 

  • Jungmann PM, Mehlhorn AT, Schmal H, Schillers H, Oberleithner H, Süedkamp NP (2012) Nanomechanics of human adipose-derived stem cells: small GTPases impact chondrogenic differentiation. Tissue Eng A 18(9–10):1035–1044. doi:10.1089/ten.tea.2011.0507

    Google Scholar 

  • Kim YJ, Sah RLY, Grodzinsky AJ, Plaas AHK, Sandy JD (1994) Mechanical regulation of cartilage biosynthetic behavior: physical stimuli. Arch Biochem Biophys 311(1):1–12. doi:10.1006/abbi.1994.1201

    Google Scholar 

  • Kopesky PW, Lee H-Y, Vanderploeg EJ, Kisiday JD, Frisbie DD, Plaas AHK, Ortiz C, Grodzinsky AJ (2010) Adult equine bone marrow stromal cells produce a cartilage-like ECM mechanically superior to animal-matched adult chondrocytes. Matrix Biol 29(5):427–438. doi:10.1016/j.matbio.2010.02.003

    Google Scholar 

  • Kuhbier JW, Weyand B, Radtke C, Vogt PM, Kasper C, Reimers K (2010) Isolation, characterization, differentiation, and application of adipose-derived stem cells. In: Kasper C, VanGriensven M, Portner R (eds) Bioreactor systems for tissue engineering II: strategies for the expansion and directed differentiation of stem cells, vol 123. Advances in Biochemical Engineering/Biotechnology, pp 55–105. doi:10.1007/10_2009_24

  • Langer R, Vacanti JP (1993) Tissue engineering. Science 260(5110):920–926. doi:10.1126/science.8493529

    Google Scholar 

  • Lee B, Han L, Frank EH, Chubinskaya S, Ortiz C, Grodzinsky AJ (2010a) Dynamic mechanical properties of the tissue-engineered matrix associated with individual chondrocytes. J Biomech 43(3):469–476. doi:10.1016/j.jbiomech.2009.09.053

    Google Scholar 

  • Lee CR, Grodzinsky AJ, Hsu H-P, Martin SD, Spector M (2000) Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee. J Orthop Res 18(5):790–799. doi:10.1002/jor.1100180517

    Google Scholar 

  • Lee H-Y, Han L, Roughley PJ, Grodzinsky AJ, Ortiz C (2013) Age-related nanostructural and nanomechanical changes of individual human cartilage aggrecan monomers and their glycosaminoglycan side chains. J Struct Biol 181(3):264–273. doi:10.1016/j.jsb.2012.12.008

    Google Scholar 

  • Lee H-Y, Kopesky PW, Plaas AHK, Sandy JD, Kisiday J, Frisbie D, Grodzinsky AJ, Ortiz C (2010b) Adult bone marrow stromal cell-based tissue-engineered aggrecan exhibits ultrastructure and nanomechanical properties superior to native cartilage. Osteoarthritis Cartilage 18(11):1477–1486. doi:10.1016/j.joca.2010.07.015

    Google Scholar 

  • Lima EG, Tan AR, Tai T, Bian L, Stoker AM, Ateshian GA, Cook JL, Hung CT (2008) Differences in interleukin-1 response between engineered and native cartilage. Tissue Eng A 14(10):1721–1730. doi:10.1089/ten.tea.2007.0347

    Google Scholar 

  • Lin DC, Horkay F (2008) Nanomechanics of polymer gels and biological tissues: a critical review of analytical approaches in the Hertzian regime and beyond. Soft Matter 4(4):669–682. doi:10.1039/b714637j

    Google Scholar 

  • Liu X, Sun JQ, Heggeness MH, Yeh M-L, Luo Z-P (2004) Direct quantification of the rupture force of single hyaluronan/hyaluronan binding protein bonds. FEBS Lett 563(1–3):23–27. doi:10.1016/S0014-5793(04)00232-7

    Google Scholar 

  • Liu X, Yeh M-L, Lewis JL, Luo Z-P (2005) Direct measurement of the rupture force of single pair of decorin interactions. Biochem Biophys Res Commun 338(3):1342–1345. doi:10.1016/j.bbrc.2005.10.096

    Google Scholar 

  • Loeser RF, Pacione CA, Chubinskaya S (2003) The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum 48(8):2188–2196. doi:10.1002/art.11209

    Google Scholar 

  • Loparic M, Wirz D, Daniels AU, Raiteri R, VanLandingham MR, Guex G, Martin I, Aebi U, Stolz M (2010) Micro- and nanomechanical analysis of articular cartilage by indentation-type atomic force microscopy: validation with a gel-microfiber composite. Biophys J 98(11):2731–2740. doi:10.1016/j.bpj.2010.02.013

    Google Scholar 

  • Mahaffy RE, Park S, Gerde E, Kas J, Shih CK (2004) Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys J 86(3):1777–1793. doi:10.1016/S0006-3495(04)74245-9

    Google Scholar 

  • Mahaffy RE, Shih CK, MacKintosh FC, Kas J (2000) Scanning probe-based frequency-dependent microrheology of polymer gels and biological cells. Phys Rev Lett 85(4):880–883. doi:10.1103/PhysRevLett.85.880

    Google Scholar 

  • Mankin HJ (1982) The response of articular cartilage to mechanical injury. J Bone Joint Surg Am 64(3):460–466

    Google Scholar 

  • Maroudas A (1979) Physicochemical properties of articular cartilage. In: Freeman MAR (ed) Adult articular cartilage. Pitman, England, pp 215–290

    Google Scholar 

  • McLeod MA, Wilusz RE, Guilak F (2013) Depth-dependent anisotropy of the micromechanical properties of the extracellular and pericellular matrices of articular cartilage evaluated via atomic force microscopy. J Biomech 46(3):586–592. doi:10.1016/j.jbiomech.2012.09.003

    Google Scholar 

  • McQuillan DJ, Handley CJ, Campbell MA, Bolis S, Milway VE, Herington AC (1986) Stimulation of proteoglycan biosynthesis by serum and insulin-like growth factor-I in cultured bovine articular cartilage. Biochem J 240(2):423–430

    Google Scholar 

  • Meachim G, Stockwell RA (1979) The matrix. In: Freeman MAR (ed) Adult articular cartilage. Pitnam Medical, London, pp 1–68

    Google Scholar 

  • Mow VC, Kuei SC, Lai WM, Armstrong CG (1980) Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments. J Biomech Eng 102(1):73–84. doi:10.1115/1.3138202

    Google Scholar 

  • Muir IHM (1979) Biochemistry. In: Freeman MAR (ed) Adult articular cartilage. Pitman Medical, Kent, pp 145–214

    Google Scholar 

  • Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F (2002) Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum 46(3):704–713. doi:10.1002/art.10118

    Google Scholar 

  • Nagase H, Kashiwagi M (2003) Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 5(2):94–103. doi:10.1186/ar630

    Google Scholar 

  • Ng L, Grodzinsky AJ, Patwari P, Sandy J, Plaas A, Ortiz C (2003) Individual cartilage aggrecan macromolecules and their constituent glycosaminoglycans visualized via atomic force microscopy. J Struct Biol 143(3):242–257. doi:10.1016/j.jsb.2003.08.006

    Google Scholar 

  • Ng L, Hung H-H, Sprunt A, Chubinskaya S, Ortiz C, Grodzinsky A (2007) Nanomechanical properties of individual chondrocytes and their developing growth factor-stimulated pericellular matrix. J Biomech 40(5):1011–1023. doi:10.1016/j.jbiomech.2006.04.004

    Google Scholar 

  • Nia HT, Bozchalooi IS, Li Y, Han L, Hung H-H, Frank EH, Youcef-Toumi K, Ortiz C, Grodzinsky AJ (2013) High-bandwidth AFM-based rheology reveals that cartilage is most sensitive to high loading rates at early stages of impairment. Biophys J 104(7):1529–1537. doi:10.1016/j.bpj.2013.02.048

    Google Scholar 

  • Nia HT, Han L, Li Y, Ortiz C, Grodzinsky AJ (2011) Poroelasticity of cartilage at the nanoscale. Biophys J 101(9):2304–2313. doi:10.1016/j.bpj.2011.09.011

    Google Scholar 

  • Nishida Y, Knudson CB, Kuettner KE, Knudson W (2000) Osteogenic protein-1 promotes the synthesis and retention of extracellular matrix within bovine articular cartilage and chondrocyte cultures. Osteoarthritis Cartilage 8(2):127–136. doi:10.1053/joca.1999.0281

    Google Scholar 

  • Nöth U, Steinert A, Tuan RS (2008) Technology insight: adult mesenchymal stem cells for osteoarthritis therapy. Nat Clin Pract Rheumatol 4(7):371–380. doi:10.1038/ncprheum0816

    Google Scholar 

  • Oliver WC, Pharr GM (1992) An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J Mater Res 7(6):1564–1583. doi:10.1557/jmr.1992.1564

    Google Scholar 

  • Ongaro A, Pellati A, Setti S, Masieri FF, Aquila G, Fini M, Caruso A, DeMattei M (2012) Electromagnetic fields counteract IL-1β activity during chondrogenesis of bovine mesenchymal stem cells. J Tissue Eng Regen Med. doi:10.1002/term.1671

  • Oshita H, Sandy JD, Suzuki K, Akaike A, Bai Y, Sasaki T, Shimizu K (2004) Mature bovine articular cartilage contains abundant aggrecan that is C-teminally truncated at Ala719-Ala720, a site which is readily cleaved by m-caplain. Biochem J 382(1):253–259. doi:10.1042/BJ20040113

    Google Scholar 

  • Park I-H, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886. doi:10.1016/j.cell.2008.07.041

    Google Scholar 

  • Park S, Costa KD, Ateshian GA (2004) Microscale frictional response of bovine articular cartilage from atomic force microscopy. J Biomech 37(11):1679–1687. doi:10.1016/j.jbiomech.2004.02.017

    Google Scholar 

  • Pearle AD, Warren RF, Rodeo SA (2005) Basic science of articular cartilage and osteoarthritis. Clin Sports Med 24(1):1–12. doi:10.1016/j.csm.2004.08.007

    Google Scholar 

  • Peñuela L, Wolf F, Raiteri R, Wendt D, Martin I, Barbero A (2014) Atomic force microscopy to investigate spatial patterns of response to interleukin-1beta in engineered cartilage tissue elasticity. J Biomech 47(9):2157–2164. doi:10.1016/j.jbiomech.2013.10.056

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147. doi:10.1126/science.284.5411.143

    Google Scholar 

  • Plaas AHK, Sandy JD (1984) Age-related decrease in the link-stability of proteoglycan aggregates formed by articular chondrocytes. Biochem J 220(1):337–340

    Google Scholar 

  • Poole CA, Ayad S, Gilbert RT (1992) Chondrons from articular-cartilage. V. Immunohistochemical evaluation of type VI collagen organization in isolated chondrons by light, confocal and electron-microscopy. J Cell Sci 103(4):1101–1110

    Google Scholar 

  • Poole CA, Flint MH, Beaumont BW (1988) Chondrons extracted from canine tibial cartilage: preliminary report on their isolation and structure. J Orthop Res 6(3):408–419

    Google Scholar 

  • Riesle J, Hollander AP, Langer R, Freed LE, Vunjak-Novakovic G (1998) Collagen in tissue-engineered cartilage: types, structure, and crosslinks. J Cell Biochem 71(3):313–327. doi:10.1002/(sici)1097-4644(19981201)71:3<313:aid-jcb1>3.0.co;2-c

    Google Scholar 

  • Rojas FP, Batista MA, Lindburg CA, Dean D, Grodzinsky AJ, Ortiz C, Han L (2014) Molecular adhesion between cartilage extracellular matrix macromolecules. Biomacromolecules 15(3):772–780. doi:10.1021/bm401611b

  • Scharstuhl A, Schewe B, Benz K, Gaissmaier C, Bühring HJ, Stoop R (2007) Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology. Stem Cells 25(12):3244–3251. doi:10.1634/stemcells.2007.0300

    Google Scholar 

  • Schmidt TA, Gastelum NS, Nguyen QT, Schumacher BL, Sah RL (2007) Boundary lubrication of articular cartilage: role of synovial fluid constituents. Arthritis Rheum 56(3):882–891. doi:10.1002/art.22446

    Google Scholar 

  • Schulz RM, Bader A (2007) Cartilage tissue engineering and bioreactor systems for the cultivation and stimulation of chondrocytes. Eur Biophys J 36(4–5):539–568. doi:10.1007/s00249-007-0139-1

    Google Scholar 

  • Scotti C, Osmokrovic A, Wolf F, Miot S, Peretti GM, Barbero A, Martin I (2012) Response of human engineered cartilage based on articular or nasal chondrocytes to interleukin-1β and low oxygen. Tissue Eng A 18(3–4):362–372. doi:10.1089/ten.tea.2011.0234

    Google Scholar 

  • Seog J, Dean D, Plaas AHK, Wong-Palms S, Grodzinsky AJ, Ortiz C (2002) Direct measurement of glycosaminoglycan intermolecular interactions via high-resolution force spectroscopy. Macromolecules 35(14):5601–5615. doi:10.1021/ma0121621

    Google Scholar 

  • Seog J, Dean D, Rolauffs B, Wu T, Genzer J, Plaas AHK, Grodzinsky AJ, Ortiz C (2005) Nanomechanics of opposing glycosaminoglycan macromolecules. J Biomech 38(9):1789–1797. doi:10.1016/j.jbiomech.2004.09.010

    Google Scholar 

  • Seog J, Dean DM, Frank EH, Ortiz C, Grodzinsky AJ (2004) Preparation of end-grafted polyelectrolytes on nanoscale probe tips using an electric field. Macromolecules 37(3):1156–1158. doi:10.1021/ma0352274

    Google Scholar 

  • Seror J, Merkher Y, Kampf N, Collinson L, Day AJ, Maroudas A, Klein J (2012) Normal and shear interactions between hyaluronan-aggrecan complexes mimicking possible boundary lubricants in articular cartilage in synovial joints. Biomacromolecules 13(11):3823–3832. doi:10.1021/bm301283f

    Google Scholar 

  • Setton LA, Zhu W, Mow VC (1993) The biphasic poroviscoelastic behavior of articular cartilage: role of the surface zone in governing the compressive behavior. J Biomech 26(4–5):581–592. doi:10.1016/0021-9290(93)90019-b

    Google Scholar 

  • Shieh AC, Koay EJ, Athanasiou KA (2006) Strain-dependent recovery behavior of single chondrocytes. Biomech Model Mechanobiol 5(2–3):172–179. doi:10.1007/s10237-006-0028-z

    Google Scholar 

  • Solursh M (1989) Cartilage stem-cells—regulation of differentiation. Connect Tissue Res 20(1–4):81–89. doi:10.3109/03008208909023877

    Google Scholar 

  • Soulhat J, Buschmann MD, Shirazi-Adl A (1999) A fibril network reinforced biphasic model of cartilage in uniaxial compression. J Biomech Eng 121(3):340–347. doi:10.1115/1.2798330

    Google Scholar 

  • Stockwell RA, Meachim G (1979) The chondrocytes. In: Freeman MAR (ed) Adult articular cartilage. Pitman Medical, Kent, pp 69–144

    Google Scholar 

  • Stolz M, Aebi U, Stoffler D (2007) Developing scanning probe-based nanodevices—stepping out of the laboratory into the clinic. Nanomed Nanotechnol Biol Med 3(1):53–62. doi:10.1016/j.nano.2007.01.001

    Google Scholar 

  • Stolz M, Gottardi R, Raiteri R, Miot S, Martin I, Imer R, Staufer U, Raducanu A, Düggelin M, Baschong W, Daniels AU, Friederich NF, Aszodi A, Aebi U (2009) Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol 4(3):186–192. doi:10.1038/nnano.2008.410

    Google Scholar 

  • Stolz M, Raiteri R, Daniels AU, VanLandingham MR, Baschong W, Aebi U (2004) Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation-type atomic force microscopy. Biophys J 86(5):3269–3283. doi:10.1016/S0006-3495(04)74375-1

    Google Scholar 

  • Ströbel S, Loparic M, Wendt D, Schenk AD, Candrian C, Lindberg RLP, Moldovan F, Barbero A, Martin I (2010) Anabolic and catabolic responses of human articular chondrocytes to varying oxygen percentages. Arthritis Res Ther 12(2):R34. doi:10.1186/ar2942

    Google Scholar 

  • Sun Y-L, Luo Z-P, Fertala A, An K-N (2004) Stretching type II collagen with optical tweezers. J Biomech 37(11):1665–1669. doi:10.1016/j.jbiomech.2004.02.028

    Google Scholar 

  • Tomkoria S, Masuda K, Mao J (2007) Nanomechanical properties of alginate-recovered chondrocyte matrices for cartilage regeneration. Proc Inst Mech Eng 221(5):467–473. doi:10.1243/09544119jeim205

    Google Scholar 

  • Tran-Khanh N, Hoemann CD, McKee MD, Henderson JE, Buschmann MD (2005) Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix. J Orthop Res 23(6):1354–1362. doi:10.1016/j.orthres.2005.05.009

    Google Scholar 

  • Trickey WR, Vail TP, Guilak F (2004) The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. J Orthop Res 22(1):131–139. doi:10.1016/s0736-0266(03)00150-5

    Google Scholar 

  • Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998) Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 353(1):29–36. doi:10.1006/abbi.1998.0633

    Google Scholar 

  • van Osch GJVM, van den Berg WB, Hunziker EB, Häuselmann HJ (1998) Differential effects of IGF-1 and TGFβ-2 on the assembly of proteoglycans in pericellular and territorial matrix by cultured bovine articular chondrocytes. Osteoarthritis Cartilage 6(3):187–195. doi:10.1053/joca.1998.0111

    Google Scholar 

  • Vanden Berg-Foels WS, Scipioni L, Huynh C, Wen X (2012) Helium ion microscopy for high-resolution visualization of the articular cartilage collagen network. J Microsc 246(2):168–176. doi:10.1111/j.1365-2818.2012.03606.x

    Google Scholar 

  • Varenberg M, Etsion I, Halperin G (2003) An improved wedge calibration method for lateral force in atomic force microscopy. Rev Sci Instrum 74(7):3362–3367. doi:10.1063/1.1584082

    Google Scholar 

  • Wehling N, Palmer GD, Pilapil C, Liu F, Wells JW, Mueller PE, Evans CH, Porter RM (2009) Interleukin-1β and tumor necrosis factor α inhibit chondrogenesis by human mesenchymal stem cells through NF-κB-dependent pathways. Arthritis Rheum 60(3):801–812. doi:10.1002/art.24352

    Google Scholar 

  • Wilbur JL, Kumar A, Kim E, Whitesides GM (1994) Microfabrication by microcontact printing of self-assembled monolayers. Adv Mater 6(7–8):600–604. doi:10.1002/adma.19940060719

    Google Scholar 

  • Wilusz RE, DeFrate LE, Guilak F (2012) Immunofluorescence-guided atomic force microscopy to measure the micromechanical properties of the pericellular matrix of porcine articular cartilage. J R Soc Interface 9(76):2997–3007. doi:10.1098/rsif.2012.0314

    Google Scholar 

  • Wong M, Carter DR (2003) Articular cartilage functional histomorphology and mechanobiology: a research perspective. Bone 33(1):1–13. doi:10.1016/s8756-3282(03)00083-8

    MathSciNet  Google Scholar 

  • Yoshida Y, Yamanaka S (2010) Recent stem cell advances: induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation 122(1):80–87. doi:10.1161/circulationaha.109.881433

    Google Scholar 

  • Zappone B, Greene GW, Oroudjev E, Jay GD, Israelachvili JN (2008) Molecular aspects of boundary lubrication by human lubricin: effect of disulfide bonds and enzymatic digestion. Langmuir 24(4):1495–1508. doi:10.1021/la702383n

    Google Scholar 

  • Zappone B, Ruths M, Greene GW, Jay GD, Israelachvili JN (2007) Adsorption, lubrication, and wear of lubricin on model surfaces: polymer brush-like behavior of a glycoprotein. Biophys J 92(5):1693–1708. doi:10.1529/biophysj.106.088799

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lin Han .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Han, L., Grodzinsky, A.J. (2015). Advances and Applications of Nanomechanical Tools in Cartilage Tissue Engineering. In: Zreiqat, H., Dunstan, C., Rosen, V. (eds) A Tissue Regeneration Approach to Bone and Cartilage Repair. Mechanical Engineering Series. Springer, Cham. https://doi.org/10.1007/978-3-319-13266-2_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-13266-2_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-13265-5

  • Online ISBN: 978-3-319-13266-2

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics