# Advances in Tissue Engineering for Disc Repair  
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treatments include disectomy to remove a herniated disc, spinal fusion surgery used to connect two vertebrae to limit the movement of the spinal motion segment, and artificial disc replacements designed to restore and maintain range of motion [8; 9]. However, spinal fusion surgery does not restore the previous range of motion and mechanical load-bearing properties of the IVD. Moreover, spinal fusion can lead to adjacent segment disease, which is a typical long-term complication after spinal fusion surgery and further indicates disc herniation, spinal canal stenosis, or spondylosis at levels above or below the index fusion level [10]. Therefore, alternate biological therapies are needed prior to surgery to slow or reverse the progression of IVDD, which usually leads to pain and disability. The mechanical properties of the IVD are critical for proper functioning. In vivo, the IVD is the load-bearing structure of the spine and is subjected to spinal tension, torsion, compression, and bending [11]. Anatomically, the normal IVD consists of the following three parts: (1) the nucleus pulposus (NP), which contains a highly hydrated gel-like matrix comprising PGs and type II collagen; (2) the annulus fibrosus (AF), which is composed of lamellae in which parallel type I collagen fibers located within each lamella are aligned and help the IVD maintain its integrity from bending, stretching, and twisting; and (3) the end plates (EP), which consist of osseous and two hyaline cartilages [12] (Figure 1). In recent years, the understanding of IVD development, cell biology, and mechanisms of IVD degeneration has significantly advanced, enabling the development of biological approaches for IVD regeneration [4]. Biological approaches include growth factor injection and gene and cell-based therapies, whereas tissue engineering approaches involve the restoration of the mechanical and biological properties of the tissue via the addition of biomaterials to the degenerated disc [13]. Depending on the stage of IVDD, different treatment strategies for managing IVDD have been recommended [14]. Initial IVDD shows change in the NP and AF matrices, while IVDD induces progressive structural changes such as annular fissures, disc herniation, disc height reduction, and disc space collapse. The Pfirrmann Disc Grading is a useful scoring tool for evaluating IVDD on MRI T2-weighted images; Grade I: homogeneous disc with bright high intensity and normal disc height; Grade II: inhomogeneous disc but high intensity signal, clear distinction between NP and AF, and normal disc height; Grade III: inhomogeneous disc with an intermittent gray signal intensity, unclear distinction between NP and AF, and normal or slightly reduced disc height; Grade IV: inhomogeneous disc with low intensity dark gray signal intensity, no more distinction between the NP and AF, and slightly or moderately decreased disc height; Grade V: inhomogeneous disc with a hypointense black signal intensity, no more distinction between the nucleus and annulus, and collapsed disc space [15]. For severe nerve compression due to herniated disc and disc space collapse (Pfirrmann grades IV and V), surgical removal of herniated disc  
Figure 1: Schematic diagram of the intervertebral disc (IVD). (**a**) sagittal cross-section (**b**) axial cross-section. and/or spinal fusion surgery are required. However, patients with discosgenic LBP due to Pfirrmann grade II and III IVDD may receive regenerative molecular therapies such as growth factors, genes, and cell therapy with or without biomaterials. In addition, tissue engineered NP and AF could be applied for patients with Pfirrmann grades IV and V.  
The aim of this review was to provide an overview of the current status of tissue engineering applications for the treatment of IVD regeneration.