Tissue engineered intervertebral disc repair in the pig using injectable polymers

The intervertebral disc (IVD) has a central nucleus pulposus (NP) able to resist compressive loads and an outer annulus fibrosus which withstands tension and gives mechanical strength. The tissue engineering of a disc substitute represents a challenge from mechanical and biological (nutrition and transport) points of view. Two hyaluronan-derived polymeric substitute materials, HYAFF® 120, an ester and HYADD® 3, an amide were injected into the NP of the lumbar spine of female pigs (11.1 ± 1.0 Kg) in which a nucleotomy had also been performed. Homologous bone marrow stem cells, obtained from the bone marrow three weeks before spinal surgery, were included in the HYADD® 3 material (1× 106 cells/ml). Two lumbar discs were operated in each animal. Control discs received a nucleotomy only. The animals were killed after 6 weeks and the lumbar spines recovered for histopathological study.Nucleotomy resulted in loss of normal IVD structure with narrowing, fibrous tissue replacement and disruption of the bony end-plates (4/4). By contrast, both HYAFF® 120 (4/4) and HYADD 3® (4/4) treatment prevented this change. The injected discs had a central NP-like region which had a close similarity to the normal biconvex structure and contained viable chondrocytes forming matrix like that of normal disc.

[1]  T. Hardingham,et al.  The specific interaction of hyaluronic acid with cartillage proteoglycans. , 1972, Biochimica et biophysica acta.

[2]  H. Inoue Three-Dimensional Architecture of Lumbar Intervertebral Discs , 1981, Spine.

[3]  M. Ishihara,et al.  An Experimental Study of the Regeneration of the Intervertebral Disc With an Allograft of Cultured Annulus Fibrosus Cells Using a Tissue-Engineering Method , 2003, Spine.

[4]  H A Yuan,et al.  The artificial disc: theory, design and materials. , 1996, Biomaterials.

[5]  K. Kivirikko,et al.  [Biosynthesis of collagen and its disorders]. , 1979, Duodecim; laaketieteellinen aikakauskirja.

[6]  D. S. Hickey,et al.  X-ray diffraction studies of the arrangement of collagenous fibres in human fetal intervertebral disc. , 1980, Journal of anatomy.

[7]  M. Pfeiffer,et al.  Intradiscal application of hyaluronic acid in the non-human primate lumbar spine: radiological results , 2003, European Spine Journal.

[8]  V. Goldberg,et al.  The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells* , 1998, The Journal of bone and joint surgery. American volume.

[9]  J. Mochida,et al.  The Importance of Preserving Disc Structure in Surgical Approaches to Lumbar Disc Herniation , 1996, Spine.

[10]  Peter Griss,et al.  Evaluation of indication-based use of transpedicular instrumentations with different rigidity for lumbar spinal fusion: a prospective pilot study with 3 years of follow-up , 2003, European Spine Journal.