The aim of this pilot study was to test a new customized biomimetic composite scaffolds to restore bone defects using CAD–CAM technology. The new biomaterial was synthesized using biomimetic mineralized collagen, and poly (ɛ-caprolactone) (PCL). The mold used in scaffolding, the surgical guide, and the bony plate used during the surgery, were rapid prototyped (CAD–CAM technology). Our in vitro results showed that sheep mesenchymal stem cells (MSC) seeding efficiency was very high (>94%). Furthermore, cells can adhere, grow and maintain cell viability up to 7 days of in vitro cultivation on the scaffold as revealed by SEM and confocal laser scanning microscope analysis. These results are indicative of good scaffold biocompatibility. The use of the sheep experimental model allowed exploring the efficacy of the customized bony plate used to give extra mechanical support to the scaffold, the potential of CAD–CAM technology in customization of the scaffold, and the in vivo biomimetic properties of the composite biomaterial.