Table 3.

Existing scaffolding approaches, insufficiencies and future directions for IVD tissue engineering

Stage of disc degeneration	Existing scaffolding approaches	Insufficiencies	Proposed future directions
Early degeneration	Injection of cells with and without hydrogel carriers (Approach 4)	Poor engraftment and viability	Improved viscosity and stiffness of carriers to reduce leakage and extrusion; welding or bioglue techniques to prevent leakage and extrusion
Mid-stage degeneration	Implantation of cell-seeded pre-made porous scaffolds (Approach 1) Implantation of cell-seeded decellularized ECM (Approach 2) Injection of cells with hydrogel carriers to replace loss in matrix (Approach 4)	Lack of in vivo model; extrusion of implants under loading	Welding or bioglue techniques to prevent leakage and extrusion; technologies to enhance the mechanical properties of scaffolds without compromising the cell viability
Late degeneration	Allogenic whole disc for total disc replacement; (Approach 2) Building interface between multiple tissue components	Short-term maintenance of disc height and hydration; degeneration of allograft in long term; lack of remodeling cells	Better graft preservation technologies to maintain matrix composition; scaffolds providing appropriate microenvironment for cells to remodel upon mechanical stimulationImprovement of proteoglycan retention in scaffolds for nucleus replacements; improvement of scaffold mechanical properties for stable annulus replacements; combinatory approach for IVD scaffolding; engineering of stable tissue interfaces