A major cause of neck and low back pains, degenerative disc disease (DDD) has become a prevailing health problem worldwide and significantly contributes to healthcare expenditures. Current conservative or surgical treatments for DDD can hardly reverse the biological function of degenerated intervertebral disc (IVD) and in some cases, may even lead to degenerative changes in adjacent vertebrae. In the last two decades, there has been a surge of interest in fabricating IVD replacements using tissue engineering strategies for DDD therapy. However, major challenge remains toward fabricating annulus fibrosus (AF) replacements that are biologically and functionally comparable to native tissue, largely due to the tremendous complexity of AF tissue at cellular, biochemical, microstructural, and biomechanical aspects. In recent years, we have employed a combination of tissue engineering strategies including layer-by-layer assembly, multimodal mechano-regulation, controlled drug delivery, and 3D printing in order to address the heterogeneity feature of AF tissue toward effective IVD regeneration. Findings from these studies may provide new insights toward developing engineered IVDs whose biological features and mechanical functions approximate those of native tissue.
