We developed a model to test new bone constructs to replace spare skeletal segments originating from new generation scaffolds for bone marrow-derived mesenchymal stem cells. Using computed tomography (CT) data, scaffolds were defined using computer-aided design/computer-aided manufacturing (CAD/CAM) for rapid prototyping by three-dimensional (3D) printing. A bone defect was created in pig mandible ramus by condyle resection for CT and CAD/CAM elaboration of bone volume for cutting and scaffold restoration. The protocol produced a perfect-fitting bone substitute model for rapid prototyped hydroxyapatite (HA) scaffolds. A surgical guide system was developed to accurately reproduce virtually planned bone sectioning procedures in animal models to obtain a perfect fit during surgery.