The degeneration of the intervertebral disc (IVD) may be considered as one of the most important musculoskeletal diseases burden. The aim of the present work was to propose a strategy to the design of nucleus/annulus tissue-engineered scaffolds for IVD regeneration. Collagen-low molecular weight hyaluronic acid (LMWHA, supplied by Anika) loaded with specific nanospheres (NPs) was suitably prepared. Human Mesenchymal Stem Cells (hMSCs) were also used to prepare cell-loaded collagen-based gels. Rheological measurements and injectability tests were performed on cell-loaded gels at different times after cell seeding. One-piece models of 3D rapid prototyped nucleus/annulus scaffolds were also properly designed and developed. These models were fabricated through 3D fiber deposition technique, using a 3D plotter equipped with a CAD/CAM system. Poly(ε-caprolactone) (PCL) pellets were initially placed in a stainless steel syringe and, then, heated through a cartridge unit placed on the mobile arm of the XYZ plotter. 3D nucleus/annulus scaffolds were obtained by alternatively extruding and depositing the PCL fibres using a specific lay-down pattern. The cell-loaded gel was then used to properly fill the nucleus and annulus regions of the 3D rapid prototyped scaffold. The formation of the cell-loaded gel was directly induced into the 3D scaffold. Compression tests were performed on cell loaded substitutes at different times after cell seeding. Cell loaded substitutes were analyzed at different days after cell seeding, using microscopy and crystal violet assay. In particular, the distribution of the cell-loaded collagen-based gel into the 3D PCL nucleus/annulus rapid prototyped scaffold was suitably observed through a stereomicroscope.