Innovative tissue engineering advances for early and late intervertebral disc degeneration repair

Abstract

Intervertebral disc (IVD) degeneration is one of the major causes of chronic back pain. It accounts for 40% of cases and is associated with disability affecting quality of life of patients worldwide. Despite the substantial economic and healthcare impact and advancement in diagnostic tools, the currently available therapeutic strategies remain limited. Tissue engineering (TE) is an emerging field that has focused on the development of reparative and regeneration strategies to improve, maintain, and restore the function and structure of the spine. In the early stages of disc degeneration, where the disc structure is still intact, minimal evidence of degeneration can be observed. Cell-based therapy using an appropriate cell source, along with a suitable soft injectable carrier, can be a promising option to repair the biology and regenerate the disc, preserving it from further degeneration and improving the associated symptoms. However, once the disc reaches the late stages of degeneration, loss of disc height, space narrowing, disc fibrosis, and formation of bone erosions will occur, and surgical interventions will likely become unavoidable if other therapeutic modalities have failed. Filling the disc space with bone grafts or metallic cages is usually a standard technique along with fusion surgery to increase stability and restore the spine alignment. TE using three-dimensional (3D) printing technology offers a better approach for overcoming the limitations associated with bone grafts and metallic cages to fill the disc space. The present thesis hypothesized that using nucleus pulposus cells (NP)-seeded Poly(N-isopropylacrylamide)-grafted hyaluronan (HA-pNIPAM) hydrogel as a cell-based therapy will help repair early-stage IVD degeneration. However, in late stages, 3D-printed scaffolds represent a promising candidate as custom, on-site substitute material for better surgical outcomes.