Skip to main content
Top
Published in: European Spine Journal 11/2007

01-11-2007 | Original Article

Material properties in unconfined compression of human nucleus pulposus, injectable hyaluronic acid-based hydrogels and tissue engineering scaffolds

Authors: Jordan M. Cloyd, Neil R. Malhotra, Lihui Weng, Weiliam Chen, Robert L. Mauck, Dawn M. Elliott

Published in: European Spine Journal | Issue 11/2007

Login to get access

Abstract

Surgical treatment for lower back pain related to degenerative disc disease commonly includes discectomy and spinal fusion. While surgical intervention may provide short-term pain relief, it results in altered biomechanics of the spine and may lead to further degenerative changes in adjacent segments. One non-fusion technique currently being investigated is nucleus pulposus (NP) support via either an injectable hydrogel or tissue engineered construct. A major challenge for either approach is to mimic the mechanical properties of native NP. Here we adopt an unconfined compression testing configuration to assess toe-region and linear-region modulus and Poisson’s ratio, key functional parameters for NP replacement. Human NP, experimental biocompatible hydrogel formulations composed of hyaluronic acid (HA), PEG-g-chitosan, and gelatin, and conventional alginate and agarose gels were investigated as injectable NP replacements or tissue engineering scaffolds. Testing consisted of a stress-relaxation experiment of 5% strain increments followed by 5-min relaxation periods to a total of 25% strain. Human NP had an average linear-region modulus of 5.39 ± 2.56 kPa and a Poisson’s ratio of 0.62 ± 0.15. The modulus and Poisson’s ratio are important parameters for evaluating the design of implant materials and scaffolds. The synthetic HA-based hydrogels approximated NP well and may serve as suitable NP implant materials.
Literature
1.
go back to reference Argoubi M, Shirazi-Adl A (1996) Poroelastic creep response analysis of a lumbar motion segment in compression. J Biomech 29:1331–1339PubMedCrossRef Argoubi M, Shirazi-Adl A (1996) Poroelastic creep response analysis of a lumbar motion segment in compression. J Biomech 29:1331–1339PubMedCrossRef
2.
go back to reference Ateshian GA, Chahine NO, Basalo IM, Hung CT (2004) The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage. J Biomech 37:391–400PubMedCrossRef Ateshian GA, Chahine NO, Basalo IM, Hung CT (2004) The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage. J Biomech 37:391–400PubMedCrossRef
3.
go back to reference Bain A, Sherman T, Norton B (2000) A comparison of the viscoelastic behavior of the lumbar intervertebral disc before and after the implantation of a prosthetic disc nucleus. In: Advances in bioengineering. ASME, New Orleans, pp 203–204 Bain A, Sherman T, Norton B (2000) A comparison of the viscoelastic behavior of the lumbar intervertebral disc before and after the implantation of a prosthetic disc nucleus. In: Advances in bioengineering. ASME, New Orleans, pp 203–204
4.
go back to reference Bao QB, McCullen GM, Higham PA, Dumbleton JH, Yuan HA (1996) The artificial disc: theory, design and materials. Biomaterials 17:1157–1167PubMedCrossRef Bao QB, McCullen GM, Higham PA, Dumbleton JH, Yuan HA (1996) The artificial disc: theory, design and materials. Biomaterials 17:1157–1167PubMedCrossRef
5.
6.
go back to reference Bao QB, Yuan HA (2002) Prosthetic disc replacement: the future? Clin Orthop Relat Res 394:139–145PubMedCrossRef Bao QB, Yuan HA (2002) Prosthetic disc replacement: the future? Clin Orthop Relat Res 394:139–145PubMedCrossRef
7.
go back to reference Bertagnoli R, Sabatino CT, Edwards JT, Gontarz GA, Prewett A, Parsons JR (2005) Mechanical testing of a novel hydrogel nucleus replacement implant. Spine J 5:672–681PubMedCrossRef Bertagnoli R, Sabatino CT, Edwards JT, Gontarz GA, Prewett A, Parsons JR (2005) Mechanical testing of a novel hydrogel nucleus replacement implant. Spine J 5:672–681PubMedCrossRef
8.
go back to reference Boyd LM, Carter AJ (2006) Injectable biomaterials and vertebral endplate treatment for repair and regeneration of the intervertebral disc. Eur Spine J 15(Suppl 3):414–421CrossRef Boyd LM, Carter AJ (2006) Injectable biomaterials and vertebral endplate treatment for repair and regeneration of the intervertebral disc. Eur Spine J 15(Suppl 3):414–421CrossRef
9.
go back to reference Chen W, Abrahams J Biopolymer systems for tissue sealing. In: US11/379 (ed) Chen W, Abrahams J Biopolymer systems for tissue sealing. In: US11/379 (ed)
10.
go back to reference Chen W, Abrahams J Composition and method for vascular embolization. In: US11/447 (ed) Chen W, Abrahams J Composition and method for vascular embolization. In: US11/447 (ed)
11.
go back to reference Di Martino A, Vaccaro AR, Lee JY, Denaro V, Lim MR (2005) Nucleus pulposus replacement: basic science and indications for clinical use. Spine 30:S16–S22PubMedCrossRef Di Martino A, Vaccaro AR, Lee JY, Denaro V, Lim MR (2005) Nucleus pulposus replacement: basic science and indications for clinical use. Spine 30:S16–S22PubMedCrossRef
12.
go back to reference Drury JL, Dennis RG, Mooney DJ (2004) The tensile properties of alginate hydrogels. Biomaterials 25:3187–3199PubMedCrossRef Drury JL, Dennis RG, Mooney DJ (2004) The tensile properties of alginate hydrogels. Biomaterials 25:3187–3199PubMedCrossRef
13.
go back to reference Elliott DM, Guilak F, Vail TP, Wang JY, Setton LA (1999) Tensile properties of articular cartilage are altered by meniscectomy in a canine model of osteoarthritis. J Orthop Res 17:503–508PubMedCrossRef Elliott DM, Guilak F, Vail TP, Wang JY, Setton LA (1999) Tensile properties of articular cartilage are altered by meniscectomy in a canine model of osteoarthritis. J Orthop Res 17:503–508PubMedCrossRef
14.
go back to reference Elliott DM, Narmoneva DA, Setton LA (2002) Direct measurement of the Poisson’s ratio of human patella cartilage in tension. J Biomech Eng 124:223–228PubMedCrossRef Elliott DM, Narmoneva DA, Setton LA (2002) Direct measurement of the Poisson’s ratio of human patella cartilage in tension. J Biomech Eng 124:223–228PubMedCrossRef
15.
go back to reference Elliott DM, Setton LA (2001) Anisotropic and inhomogeneous tensile behavior of the human anulus fibrosus: experimental measurement and material model predictions. J Biomech Eng 123:256–263PubMedCrossRef Elliott DM, Setton LA (2001) Anisotropic and inhomogeneous tensile behavior of the human anulus fibrosus: experimental measurement and material model predictions. J Biomech Eng 123:256–263PubMedCrossRef
16.
go back to reference Goel VK, Kong W, Han JS, Weinstein JN, Gilbertson LG (1993) Combined finite element and optimization investigation of lumbar spine mechanics with and without muscles. Spine 18:1531–1541PubMedCrossRef Goel VK, Kong W, Han JS, Weinstein JN, Gilbertson LG (1993) Combined finite element and optimization investigation of lumbar spine mechanics with and without muscles. Spine 18:1531–1541PubMedCrossRef
17.
go back to reference Gokorsch S, Nehring D, Grottke C, Czermak P (2004) Hydrodynamic stimulation and long term cultivation of nucleus pulposus cells: a new bioreactor system to induce extracellular matrix synthesis by nucleus pulposus cells dependent on intermittent hydrostatic pressure. Int J Artif Organs 27:962–970PubMed Gokorsch S, Nehring D, Grottke C, Czermak P (2004) Hydrodynamic stimulation and long term cultivation of nucleus pulposus cells: a new bioreactor system to induce extracellular matrix synthesis by nucleus pulposus cells dependent on intermittent hydrostatic pressure. Int J Artif Organs 27:962–970PubMed
18.
go back to reference Horner HA, Roberts S, Bielby RC, Menage J, Evans H, Urban JP (2002) Cells from different regions of the intervertebral disc: effect of culture system on matrix expression and cell phenotype. Spine 27:1018–1028PubMedCrossRef Horner HA, Roberts S, Bielby RC, Menage J, Evans H, Urban JP (2002) Cells from different regions of the intervertebral disc: effect of culture system on matrix expression and cell phenotype. Spine 27:1018–1028PubMedCrossRef
19.
go back to reference Horner HA, Urban JP (2001) 2001 Volvo award winner in basic science studies: effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine 26:2543–2549PubMedCrossRef Horner HA, Urban JP (2001) 2001 Volvo award winner in basic science studies: effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine 26:2543–2549PubMedCrossRef
20.
go back to reference Huang RC, Wright TM, Panjabi MM, Lipman JD (2005) Biomechanics of nonfusion implants. Orthop Clin North Am 36:271–280PubMedCrossRef Huang RC, Wright TM, Panjabi MM, Lipman JD (2005) Biomechanics of nonfusion implants. Orthop Clin North Am 36:271–280PubMedCrossRef
21.
go back to reference Iatridis JC, Laible JP, Krag MH (2003) Influence of fixed charge density magnitude and distribution on the intervertebral disc: applications of a poroelastic and chemical electric (PEACE) model. J Biomech Eng 125:12–24PubMedCrossRef Iatridis JC, Laible JP, Krag MH (2003) Influence of fixed charge density magnitude and distribution on the intervertebral disc: applications of a poroelastic and chemical electric (PEACE) model. J Biomech Eng 125:12–24PubMedCrossRef
22.
go back to reference Iatridis JC, Weidenbaum M, Setton LA, Mow VC (1996) Is the nucleus pulposus a solid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine 21(10):1174–1184PubMedCrossRef Iatridis JC, Weidenbaum M, Setton LA, Mow VC (1996) Is the nucleus pulposus a solid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine 21(10):1174–1184PubMedCrossRef
23.
go back to reference Johannessen W, Vresilovic EJ, Seguritan JA, Elliott DM (2004) Altered nucleus pulposus mechanics using chondroitinase-abc and genipin as a model of early disc degeneration. In: Transactions of the Orthopaedic Research Society, vol 29, p 1150 Johannessen W, Vresilovic EJ, Seguritan JA, Elliott DM (2004) Altered nucleus pulposus mechanics using chondroitinase-abc and genipin as a model of early disc degeneration. In: Transactions of the Orthopaedic Research Society, vol 29, p 1150
24.
go back to reference Johannessen W, Elliott DM (2005) Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine 30:E724–E729PubMedCrossRef Johannessen W, Elliott DM (2005) Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine 30:E724–E729PubMedCrossRef
25.
go back to reference Joshi A, Fussell G, Thomas J, Hsuan A, Lowman A, Karduna A, Vresilovic E, Marcolongo M (2006) Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials 27:176–184PubMedCrossRef Joshi A, Fussell G, Thomas J, Hsuan A, Lowman A, Karduna A, Vresilovic E, Marcolongo M (2006) Functional compressive mechanics of a PVA/PVP nucleus pulposus replacement. Biomaterials 27:176–184PubMedCrossRef
26.
go back to reference Joshi A, Mehta S, Vresilovic E, Karduna A, Marcolongo M (2005) Nucleus implant parameters significantly change the compressive stiffness of the human lumbar intervertebral disc. J Biomech Eng 127:536–540PubMedCrossRef Joshi A, Mehta S, Vresilovic E, Karduna A, Marcolongo M (2005) Nucleus implant parameters significantly change the compressive stiffness of the human lumbar intervertebral disc. J Biomech Eng 127:536–540PubMedCrossRef
27.
go back to reference Jurvelin JS, Buschmann MD, Hunziker EB (1997) Optical and mechanical determination of Poisson’s ratio of adult bovine humeral articular cartilage. J Biomech 30:235–241PubMedCrossRef Jurvelin JS, Buschmann MD, Hunziker EB (1997) Optical and mechanical determination of Poisson’s ratio of adult bovine humeral articular cartilage. J Biomech 30:235–241PubMedCrossRef
28.
go back to reference Kelly TA, Ng KW, Wang CC, Ateshian GA, Hung CT (2006) Spatial and temporal development of chondrocyte-seeded agarose constructs in free-swelling and dynamically loaded cultures. J Biomech 39:1489–1497PubMedCrossRef Kelly TA, Ng KW, Wang CC, Ateshian GA, Hung CT (2006) Spatial and temporal development of chondrocyte-seeded agarose constructs in free-swelling and dynamically loaded cultures. J Biomech 39:1489–1497PubMedCrossRef
29.
30.
go back to reference Korhonen RK, Laasanen MS, Toyras J, Rieppo J, Hirvonen J, Helminen HJ, Jurvelin JS (2002) Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. J Biomech 35:903–909PubMedCrossRef Korhonen RK, Laasanen MS, Toyras J, Rieppo J, Hirvonen J, Helminen HJ, Jurvelin JS (2002) Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. J Biomech 35:903–909PubMedCrossRef
31.
go back to reference Larson JW, Chadderon RC, Georgescu H, Lee D, Hubert M, Werkmeister-Lewis L, Irrang J, Gilbertson LG, Kang JD (2006) Prevention of intervertebral disc degeneration after surgical discectomy using an injectable nucleus pulposus prosthesis. In: Proceedings of the 52nd annual meeting of the orthopaedic research society, Chicago, p 1237 Larson JW, Chadderon RC, Georgescu H, Lee D, Hubert M, Werkmeister-Lewis L, Irrang J, Gilbertson LG, Kang JD (2006) Prevention of intervertebral disc degeneration after surgical discectomy using an injectable nucleus pulposus prosthesis. In: Proceedings of the 52nd annual meeting of the orthopaedic research society, Chicago, p 1237
32.
go back to reference Leahy JC, Hukins DWL (2001) Viscoelastic properties of the nucleus pulposus of the intervertebral disk in compression. J Mater Sci: Mater Med 12:689–692CrossRef Leahy JC, Hukins DWL (2001) Viscoelastic properties of the nucleus pulposus of the intervertebral disk in compression. J Mater Sci: Mater Med 12:689–692CrossRef
33.
go back to reference Lee CK, Kim YE, Lee CS, Hong YM, Jung JM, Goel VK (2000) Impact response of the intervertebral disc in a finite-element model. Spine 25:2431–2439PubMedCrossRef Lee CK, Kim YE, Lee CS, Hong YM, Jung JM, Goel VK (2000) Impact response of the intervertebral disc in a finite-element model. Spine 25:2431–2439PubMedCrossRef
34.
go back to reference LeRoux MA, Guilak F, Setton LA (1999) Compressive and shear properties of alginate gel: effects of sodium ions and alginate concentration. J Biomed Mater Res 47:46–53PubMedCrossRef LeRoux MA, Guilak F, Setton LA (1999) Compressive and shear properties of alginate gel: effects of sodium ions and alginate concentration. J Biomed Mater Res 47:46–53PubMedCrossRef
35.
go back to reference Lu YM, Hutton WC, Gharpuray VM (1998) The effect of fluid loss on the viscoelastic behavior of the lumbar intervertebral disc in compression. J Biomech Eng 120:48–54PubMed Lu YM, Hutton WC, Gharpuray VM (1998) The effect of fluid loss on the viscoelastic behavior of the lumbar intervertebral disc in compression. J Biomech Eng 120:48–54PubMed
36.
go back to reference Malhotra N, Beckstein J, Cloyd JM, Johannessen WJ, Chen W, Elliott DM (2006) Injectable hydrogels to support nucleus pulposus function. Pennsylvania Neurological Society, Harrisburg, PA Malhotra N, Beckstein J, Cloyd JM, Johannessen WJ, Chen W, Elliott DM (2006) Injectable hydrogels to support nucleus pulposus function. Pennsylvania Neurological Society, Harrisburg, PA
37.
go back to reference Martinez JB, Oloyede VO, Broom ND (1997) Biomechanics of load-bearing of the intervertebral disc: an experimental and finite element model. Med Eng Phys 19:145–156PubMedCrossRef Martinez JB, Oloyede VO, Broom ND (1997) Biomechanics of load-bearing of the intervertebral disc: an experimental and finite element model. Med Eng Phys 19:145–156PubMedCrossRef
38.
go back to reference Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, Hung CT, Ateshian GA (2000) Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 122:252–260PubMedCrossRef Mauck RL, Soltz MA, Wang CC, Wong DD, Chao PH, Valhmu WB, Hung CT, Ateshian GA (2000) Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng 122:252–260PubMedCrossRef
39.
go back to reference Mizuno H, Roy AK, Vacanti CA, Kojima K, Ueda M, Bonassar LJ (2004) Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine 29:1290–1297; discussion 1297–1298PubMedCrossRef Mizuno H, Roy AK, Vacanti CA, Kojima K, Ueda M, Bonassar LJ (2004) Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine 29:1290–1297; discussion 1297–1298PubMedCrossRef
40.
go back to reference Mizuno H, Roy AK, Zaporojan V, Vacanti CA, Ueda M, Bonassar LJ (2006) Biomechanical and biochemical characterization of composite tissue-engineered intervertebral discs. Biomaterials 27:362–370PubMedCrossRef Mizuno H, Roy AK, Zaporojan V, Vacanti CA, Ueda M, Bonassar LJ (2006) Biomechanical and biochemical characterization of composite tissue-engineered intervertebral discs. Biomaterials 27:362–370PubMedCrossRef
41.
go back to reference Natarajan RN, Ke JH, Andersson GBJ (1994) A model to study the disc degeneration process. Spine 19:259–265PubMedCrossRef Natarajan RN, Ke JH, Andersson GBJ (1994) A model to study the disc degeneration process. Spine 19:259–265PubMedCrossRef
42.
go back to reference Rowley JA, Mooney DJ (2002) Alginate type and RGD density control myoblast phenotype. J Biomed Mater Res 60:217–223PubMedCrossRef Rowley JA, Mooney DJ (2002) Alginate type and RGD density control myoblast phenotype. J Biomed Mater Res 60:217–223PubMedCrossRef
43.
go back to reference Sato M, Kikuchi T, Asazuma T, Yamada H, Maeda H, Fujikawa K (2001) Glycosaminoglycan accumulation in primary culture of rabbit intervertebral disc cells. Spine 26:2653–2660PubMedCrossRef Sato M, Kikuchi T, Asazuma T, Yamada H, Maeda H, Fujikawa K (2001) Glycosaminoglycan accumulation in primary culture of rabbit intervertebral disc cells. Spine 26:2653–2660PubMedCrossRef
44.
go back to reference Shirazi-Adl A (1989) On the fibre composite material models of disc annulus—comparison of predicted stresses. J Biomech 22:357–365PubMedCrossRef Shirazi-Adl A (1989) On the fibre composite material models of disc annulus—comparison of predicted stresses. J Biomech 22:357–365PubMedCrossRef
45.
go back to reference Thomas J, Lowman A, Marcolongo M (2003) Novel associated hydrogels for nucleus pulposus replacement. J Biomed Mater Res A 67:1329–1337PubMedCrossRef Thomas J, Lowman A, Marcolongo M (2003) Novel associated hydrogels for nucleus pulposus replacement. J Biomed Mater Res A 67:1329–1337PubMedCrossRef
46.
go back to reference Thonar E, An H, Masuda K (2002) Compartmentalization of the matrix formed by nucleus pulposus and annulus fibrosus cells in alginate gel. Biochem Soc Trans 30:874–878PubMedCrossRef Thonar E, An H, Masuda K (2002) Compartmentalization of the matrix formed by nucleus pulposus and annulus fibrosus cells in alginate gel. Biochem Soc Trans 30:874–878PubMedCrossRef
47.
go back to reference Umehara S, Tadano S, Abumi K, Katagiri K, Kaneda K, Ukai T (1996) Effects of degeneration on the elastic modulus distribution in the lumbar intervertebral disc. Spine 21:811–819; discussion 820 Umehara S, Tadano S, Abumi K, Katagiri K, Kaneda K, Ukai T (1996) Effects of degeneration on the elastic modulus distribution in the lumbar intervertebral disc. Spine 21:811–819; discussion 820
48.
go back to reference Vincent J (1990) Structural biomaterials, revised edition. Princeton University Press, Princeton, NJ Vincent J (1990) Structural biomaterials, revised edition. Princeton University Press, Princeton, NJ
49.
go back to reference Wang CC, Chahine NO, Hung CT, Ateshian GA (2003) Optical determination of anisotropic material properties of bovine articular cartilage in compression. J Biomech 36:339–353PubMedCrossRef Wang CC, Chahine NO, Hung CT, Ateshian GA (2003) Optical determination of anisotropic material properties of bovine articular cartilage in compression. J Biomech 36:339–353PubMedCrossRef
50.
go back to reference Weng LH, Pan H, Chen W (2007) Crosslinked hydrogels composed of partially oxidized hyaluronan and gelatin: in vitro and in vivo responses. J Biomed Biomater Res. Part A (in press) Weng LH, Pan H, Chen W (2007) Crosslinked hydrogels composed of partially oxidized hyaluronan and gelatin: in vitro and in vivo responses. J Biomed Biomater Res. Part A (in press)
51.
go back to reference Wenger KH, Schlegel JD (1997) Annular bulge contours from an axial photogrammetric method. Clin Biomech (Bristol, Avon) 12:438–444CrossRef Wenger KH, Schlegel JD (1997) Annular bulge contours from an axial photogrammetric method. Clin Biomech (Bristol, Avon) 12:438–444CrossRef
52.
go back to reference Wilke HJ, Kavanagh S, Neller S, Haid C, Claes LE (2001) Effect of a prosthetic disc nucleus on the mobility and disc height of the L4-5 intervertebral disc postnucleotomy. J Neurosurg 95:208–214PubMed Wilke HJ, Kavanagh S, Neller S, Haid C, Claes LE (2001) Effect of a prosthetic disc nucleus on the mobility and disc height of the L4-5 intervertebral disc postnucleotomy. J Neurosurg 95:208–214PubMed
Metadata
Title
Material properties in unconfined compression of human nucleus pulposus, injectable hyaluronic acid-based hydrogels and tissue engineering scaffolds
Authors
Jordan M. Cloyd
Neil R. Malhotra
Lihui Weng
Weiliam Chen
Robert L. Mauck
Dawn M. Elliott
Publication date
01-11-2007
Publisher
Springer-Verlag
Published in
European Spine Journal / Issue 11/2007
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-007-0443-6

Other articles of this Issue 11/2007

European Spine Journal 11/2007 Go to the issue