Intervertebral disc (IVD) degeneration, which contributes to instability, deformity, and stenosis of the spinal segment, has been regarded as one of the leading causes of spondylomyelopathy, and low back pain in daily clinical practice. IVD is located in three regions: the bony and cartilaginous endplates (EPs) sandwiching the central nucleus pulposus (NP), and the peripheral annulus fibrosus (AF). IVD degeneration can be described as an aberrant, cell-mediated response to progressive structural failure of the IVD, involving pathological changes in all aforementioned structures. Because of the poor self-repair ability of tissues affected by IVD, there is no satisfactory way to reverse the IVD degeneration, and current treatment approaches are mostly salvage strategies. Techniques of regenerative therapy are very promising, although most of them are currently in the experimental phase. Ideal IVD regenerative therapies aim to restore the functional disc matrix, and prospective approaches include biotechnology, tissue engineering, and novel surgical interventions. Several in vitro, and preclinical studies have demonstrated that biotherapeutic strategies, such as cell therapy or tissue engineering, are able to synthesize the structural components of the disc matrix and improve resident cell activity.

However, due to its unique anatomical location and function, IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limits the efficacy of intradiscal cell therapy or implantation of bionic IVD in diverse investigations. Thus, more exploration of functionalised scaffolds loaded with cells, biological agents or drugs, and novel surgical methods is needed to ameliorate the adverse factors coming from the IVD microenvironment.

The aim of this Special Issue is to solicit original research articles, as well as review articles, focusing on how to overcome the obstacles of IVD regeneration by developing innovative therapeutic strategies, especially regarding biotechnology, tissue engineering, and surgical interventions. We hope that this proposal will foster discussion between researchers about the factors initiating disc degenerative processes and the promising therapeutic strategies to help disc regeneration.

Potential topics include but are not limited to the following:

• Novel mechanisms of cell death, senescence, injury, and repair involved in the process of intervertebral disc degeneration
• Novel candidates for cellular therapy to promote intervertebral disc (nucleus pulposus, end plates, or annulus fibrosus) repair, and regeneration
• Novel candidates for molecular targeted therapy to promote intervertebral disc repair and regeneration
• Novel drugs to promote intervertebral disc repair and regeneration
• Novel scaffolds or techniques used for growth factor carriers
• Novel biomaterials for intervertebral disc regeneration or reconstruction
• Novel biotechniques for intervertebral disc reconstruction
• Novel tissue engineering strategies for intervertebral disc reconstruction
• Preclinical (in vitro and in vivo) evaluation of biomechanical properties of biomaterials/scaffolds in intervertebral disc tissue regeneration