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 (1x 10(6) 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.