Modified-Hyaluronan and Elastin-Like Polypeptide Composite Material for Tissue Engineering of the Nucleus Pulposus

Degenerative disc disease is a common ailment with enormous medical, psychosocial and economic ramifications. This study was designed to investigate the utility of a thiol-modified hyaluronan(TMHA) and elastin-like polypeptide(EP) composite material as a potential tissue engineering scaffold to reconstitute the nucleus pulposus in early degenerative disc disease. TMHA and EP were combined in various concentrations and cross-linked using poly(ethylene glycol)diacrylate. Resulting materials were evaluated biomechanically and biologically. Confined compression testing revealed that the addition of EP to TMHA-based gels resulted in a stiffer construct, but remained an order of magnitude less stiff than native nucleus. The in vitro cell culture experiments with human intervertebral disc cells demonstrated 70% cell viability at three weeks with apparent maintenance of phenotype. The addition of EP did not have a significant biologic effect. An in vivo pilot study demonstrated biocompatibility of the TMHA-based hydrogels; additional power is required to adequately assess treatment effect.

Year	Entry
2001	Huang C-Y, Mow VC, Ateshian GA. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J Biomech Eng. October 2001;123(5):410-417.
1997	Ateshian GA, Warden W, Kim JJ, Grelsamer RP, Mow VC. Finite deformation biphasic material properties of bovine articular cartilage from confined compression experiments. J Biomech. November–December 1997;30:1157.
1986	Mak AF. The apparent viscoelastic behavior of articular cartilage: the contributions from the intrinsic matrix viscoelasticity and interstitial fluid flows. J Biomech Eng. May 1986;108(2):123-130.
2006	Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. August 15, 2006;31(18):2151-2161.
1996	Iatridis JC, Weidenbaum M, Setton LA, Mow VC. Is the nucleus pulposus a solid or a fluid? mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine. May 15, 1996;21(15):1174-1184.
1951	Virgin WJ. Experimental investigations into the physical properties of the intervertebral disc. J Bone Joint Surg. November 1951;33B(4):607-611.
1996	Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash: a placebo-controlled prevalence study. Spine. August 1996;21(15):1737-1744.
2005	Johannessen W, Elliott DM. Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine. December 15, 2005;30(24):E724-E729.
1980	Woo SL-Y, Simon BR, Kuei SC, Akeson WH. Quasi-linear viscoelastic properties of normal articular cartilage. J Biomech Eng. May 1980;102(2):85-90.
1971	Hayes WC, Mockros LF. Viscoelastic properties of human articular cartilage. J Appl Physiol. October 1971;31(4):562-568.
1972	Hayes WC, Keer LM, Herrmann G, Mockros LF. A mathematical analysis for indentation tests of articular cartilage. J Biomech. September 1972;5(5):541-551.
1977	Parsons JR, Black J. The viscoelastic shear behavior of normal rabbit articular cartilage. J Biomech. 1977;10(1):21-29.
1996	Ishihara H, McNally DS, Urban JP, Hall AC. Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk. J Appl Physiol. March 1996;80(3):839-846.
2006	Roberts S, Evans H, Trivedi J, Menage J. Histology and pathology of the human intervertebral disc. J Bone Joint Surg. April 2006;88A(suppl 2):10-14.
1975	Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat. September 1975;120(1):113-130.
1998	Iatridis JC, Setton LA, Foster RJ, Rawlins BA, Weidenbaum M, Mow VC. Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression. J Biomech. June 1998;31(6):535-544.
1997	Handa T, Ishihara H, Ohshima H, Osada R, Tsuji H, Obata K. Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. Spine. May 15, 1997;22(10):1085-1091.
1993	Fung YC. Biomechanics: Mechanical Properties of Living Tissues. 2nd ed. New York, NY: Springer-Verlag; 1993.
1999	Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. April 2, 1999;284(5411):143-147.
1971	Kempson GE, Freeman MAR, Swanson SAV. The determination of a creep modulus for articular cartilage from indentation tests on the human femoral head. J Biomech. July 1971;4(4):239-250.
1963	Elmore SM, Sokoloff L, Norris G, Carmeci P. Nature of “imperfect” elasticity of articular cartilage. J Appl Physiol. 1963;18(2):393-396.
1998	Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine. December 1, 1998;23(23):2493-2506.
2002	Verzijl N, DeGroot J, Ben Zaken C, Braun-Benjamin O, Maroudas A, Bank RA, Mizrahi J, Schalkwijk CG, Thorpe SR, Baynes JW, Bijlsma JWJ, Lafeber FPJG, TeKoppele JM. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. January 2002;46(1):114-123.
2004	Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine. December 1, 2004;29(23):2691-2699.
1980	Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments. J Biomech Eng. February 1980;102(1):73-84.
1990	Kwan MK, Lai WM, Mow VC. A finite deformation theory for cartilage and other soft hydrated connective tissues, I: equilibrium results. J Biomech. 1990;23(2):145-155.
1981	Horst M, Brinckmann P. Measurement of the distribution of axial stress on the end-plate of the vertebral body. Spine. May–June 1981;6(3):217-232.
1960	Nachemson A. Lumbar intradiscal pressure: experimental studies on post-mortem material. Acta Orthop Scand. 1960;31(suppl 43):1-104.
1999	Iatridis JC, Mente PL, Stokes IAF, Aronsson DD, Alini M. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine. May 15, 1999;24(10):996-1002.
2008	Raj PP. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. January–February 2008;8(1):18-44.
1990	Holmes MH, Mow VC. The nonlinear characteristics of soft gels and hydrated connective tissues in ultrafiltration. J Biomech. 1990;23(11):1145-1156.
1994	Best BA, Guilak F, Setton LA, Zhu W, Saed-Nejad F, Ratcliffe A, Weidenbaum M, Mow VC. Compressive mechanical properties of the human anulus fibrosus and their relationship to biochemical composition. Spine. January 15, 1994;19(2):212-221.
1990	Osti OL, Vernon-Roberts B, Fraser RD. Anulus tears and intervertebral disc degeneration: an experimental study using an animal model. Spine. August 1990;15(8):762-767.
1995	Drost MR, Willems P, Snijders H, Huyghe JM, Janssen JD, Huson A. Confined compression of canine annulus fibrosus under chemical and mechanical loading. J Biomech Eng. November 1995;117(4):390-396.
2000	Soltz MA, Ateshian GA. A conewise linear elasticity mixture model for the analysis of tension-compression nonlinearity in articular cartilage. J Biomech Eng. December 2000;122(6):576-586.
2000	Klisch SM, Lotz JC. A special theory of biphasic mixtures and experimental results for human annulus fibrosus tested in confined compression. J Biomech Eng. April 2000;122(2):180-188.
1993	Setton LA, Zhu W, Weidenbaum M, Ratcliffe A, Mow VC. Compressive properties of the cartilaginous end-plate of the baboon lumbar spine. J Orthop Res. March 1993;11(2):228-239.
1990	Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine. May 1990;15(5):411-415.
1963	Sokoloff L. Elasticity of articular cartilage: effect of ions and viscous solutions. Science. September 13, 1963;141(3585):1055-1057.
2001	Pfirrmann CWA, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. September 1, 2001;26(17):1873-1878.
2002	Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. Classification of age-related changes in lumbar intervertebral discs. Spine. December 1, 2002;27(23):2631-2644.

Year

Entry

2001

Huang C-Y, Mow VC, Ateshian GA. The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J Biomech Eng. October 2001;123(5):410-417.

1997

Ateshian GA, Warden W, Kim JJ, Grelsamer RP, Mow VC. Finite deformation biphasic material properties of bovine articular cartilage from confined compression experiments. J Biomech. November–December 1997;30:1157.

1986

Mak AF. The apparent viscoelastic behavior of articular cartilage: the contributions from the intrinsic matrix viscoelasticity and interstitial fluid flows. J Biomech Eng. May 1986;108(2):123-130.

2006

Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. August 15, 2006;31(18):2151-2161.

1996

Iatridis JC, Weidenbaum M, Setton LA, Mow VC. Is the nucleus pulposus a solid or a fluid? mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine. May 15, 1996;21(15):1174-1184.

1951

Virgin WJ. Experimental investigations into the physical properties of the intervertebral disc. J Bone Joint Surg. November 1951;33B(4):607-611.

1996

Lord SM, Barnsley L, Wallis BJ, Bogduk N. Chronic cervical zygapophysial joint pain after whiplash: a placebo-controlled prevalence study. Spine. August 1996;21(15):1737-1744.

2005

Johannessen W, Elliott DM. Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression. Spine. December 15, 2005;30(24):E724-E729.

1980

Woo SL-Y, Simon BR, Kuei SC, Akeson WH. Quasi-linear viscoelastic properties of normal articular cartilage. J Biomech Eng. May 1980;102(2):85-90.

1971

Hayes WC, Mockros LF. Viscoelastic properties of human articular cartilage. J Appl Physiol. October 1971;31(4):562-568.

1972

Hayes WC, Keer LM, Herrmann G, Mockros LF. A mathematical analysis for indentation tests of articular cartilage. J Biomech. September 1972;5(5):541-551.

1977

Parsons JR, Black J. The viscoelastic shear behavior of normal rabbit articular cartilage. J Biomech. 1977;10(1):21-29.

1996

Ishihara H, McNally DS, Urban JP, Hall AC. Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk. J Appl Physiol. March 1996;80(3):839-846.

2006

Roberts S, Evans H, Trivedi J, Menage J. Histology and pathology of the human intervertebral disc. J Bone Joint Surg. April 2006;88A(suppl 2):10-14.

1975

Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat. September 1975;120(1):113-130.

1998

Iatridis JC, Setton LA, Foster RJ, Rawlins BA, Weidenbaum M, Mow VC. Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression. J Biomech. June 1998;31(6):535-544.

1997

Handa T, Ishihara H, Ohshima H, Osada R, Tsuji H, Obata K. Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc. Spine. May 15, 1997;22(10):1085-1091.

1993

Fung YC. Biomechanics: Mechanical Properties of Living Tissues. 2nd ed. New York, NY: Springer-Verlag; 1993.

1999

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. April 2, 1999;284(5411):143-147.

1971

Kempson GE, Freeman MAR, Swanson SAV. The determination of a creep modulus for articular cartilage from indentation tests on the human femoral head. J Biomech. July 1971;4(4):239-250.

1963

Elmore SM, Sokoloff L, Norris G, Carmeci P. Nature of “imperfect” elasticity of articular cartilage. J Appl Physiol. 1963;18(2):393-396.

1998

Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine. December 1, 1998;23(23):2493-2506.

2002

Verzijl N, DeGroot J, Ben Zaken C, Braun-Benjamin O, Maroudas A, Bank RA, Mizrahi J, Schalkwijk CG, Thorpe SR, Baynes JW, Bijlsma JWJ, Lafeber FPJG, TeKoppele JM. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. January 2002;46(1):114-123.

2004

Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine. December 1, 2004;29(23):2691-2699.

1980

Mow VC, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and stress relaxation of articular cartilage in compression: theory and experiments. J Biomech Eng. February 1980;102(1):73-84.

1990

Kwan MK, Lai WM, Mow VC. A finite deformation theory for cartilage and other soft hydrated connective tissues, I: equilibrium results. J Biomech. 1990;23(2):145-155.

1981

Horst M, Brinckmann P. Measurement of the distribution of axial stress on the end-plate of the vertebral body. Spine. May–June 1981;6(3):217-232.

1960

Nachemson A. Lumbar intradiscal pressure: experimental studies on post-mortem material. Acta Orthop Scand. 1960;31(suppl 43):1-104.

1999

Iatridis JC, Mente PL, Stokes IAF, Aronsson DD, Alini M. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine. May 15, 1999;24(10):996-1002.

2008

Raj PP. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. January–February 2008;8(1):18-44.

1990

Holmes MH, Mow VC. The nonlinear characteristics of soft gels and hydrated connective tissues in ultrafiltration. J Biomech. 1990;23(11):1145-1156.

1994

Best BA, Guilak F, Setton LA, Zhu W, Saed-Nejad F, Ratcliffe A, Weidenbaum M, Mow VC. Compressive mechanical properties of the human anulus fibrosus and their relationship to biochemical composition. Spine. January 15, 1994;19(2):212-221.

1990

Osti OL, Vernon-Roberts B, Fraser RD. Anulus tears and intervertebral disc degeneration: an experimental study using an animal model. Spine. August 1990;15(8):762-767.

1995

Drost MR, Willems P, Snijders H, Huyghe JM, Janssen JD, Huson A. Confined compression of canine annulus fibrosus under chemical and mechanical loading. J Biomech Eng. November 1995;117(4):390-396.

2000

Soltz MA, Ateshian GA. A conewise linear elasticity mixture model for the analysis of tension-compression nonlinearity in articular cartilage. J Biomech Eng. December 2000;122(6):576-586.

2000

Klisch SM, Lotz JC. A special theory of biphasic mixtures and experimental results for human annulus fibrosus tested in confined compression. J Biomech Eng. April 2000;122(2):180-188.

1993

Setton LA, Zhu W, Weidenbaum M, Ratcliffe A, Mow VC. Compressive properties of the cartilaginous end-plate of the baboon lumbar spine. J Orthop Res. March 1993;11(2):228-239.

1990

Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine. May 1990;15(5):411-415.

1963

Sokoloff L. Elasticity of articular cartilage: effect of ions and viscous solutions. Science. September 13, 1963;141(3585):1055-1057.

2001

Pfirrmann CWA, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. September 1, 2001;26(17):1873-1878.

2002

Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. Classification of age-related changes in lumbar intervertebral discs. Spine. December 1, 2002;27(23):2631-2644.

Year	Entry
2010	Leckie AE. Mechanical Evaluation of a Thiol-Modified Hyaluronan Elastin-Like Polypeptide Nucleus Pulposus Replacement Material in Porcine Intervertebral Discs [Master's thesis]. University of Toronto; 2010.

Year

Entry

2010

Leckie AE. Mechanical Evaluation of a Thiol-Modified Hyaluronan Elastin-Like Polypeptide Nucleus Pulposus Replacement Material in Porcine Intervertebral Discs [Master's thesis]. University of Toronto; 2010.