**5. Conclusion**

rhBMP-2 dose added to the implant, 100 μg of rhBMP-2 in combination with 400 mg of the delivery system (carrier material) per animal was used in the current study. This formulation was fixed based on our previous experimental results obtained in beagle models. As widely known, a minimal dose of BMP-2 to elicit local new bone formation in *in vivo* condition depends on the animal species, and humans are less sensitive to BMP-2. Therefore, a higher BMP-2 dose to the order of a few mg will be required for bone defect repair as observed in clinical reports of rhBMP-2 used for spinal body fusion, non-union of fracture, and other off-label use of

Recent reports have described successful reconstruction of maxillary bone defects in rabbits and bone union achievement in rats with pseudarthrosis using a combination of BMP genetransfected cells and an artificial material or using sheets of cultured mesenchymal stem cells [34, 35]. However, an expensive facility equipped with a special culture system is required to establish a cell culture system for clinical application in humans. Conversely, BMPs can be conveniently used anywhere, provided that the user has adequate storage expertise. In this study, we accomplished the accurate skeletal reconstruction after resection in a virtual iliac bone tumor model in beagle dogs by combining BMP with a 3D printer, CAD, CAM, and a computer navigation system. In future, skeletal reconstruction will become possible for more

In wide resection surgery of malignant musculoskeletal tumors, optimal tumor margins and resection margin of the bone and soft tissue would be decided preoperatively on the basis of CT and/or MRI to avoid exposing the tumor tissue to the surgical field and later local recurrence of the tumor. But the accurate resection as planned preoperatively has often proven difficult. In this experimental study, a CAS system of CT-based navigation was used as a guide for bone resection margin, and the results indicated that it is possible to perform bone resection exactly as planned using the CAS system. But planning of the exact resection margin of the soft tissue covering the tumor was not attempted in this series, and similar studies based on CT and/or

The 3D configuration of the defect on the left iliac bone after resection of the virtual tumor was depicted on screen by subtraction of the 3D image of the left iliac bone from the 3D mirror image of the right iliac bone. CT data of the defect images were then transferred to the CAM system to drive the system to fabricate an IP-CHA implant to fill and fit the bone defect generated in the left iliac bone. The shape and size of the implants thus fabricated were acceptable and matched the defects well. However, the IP-CHA implant alone did not repair the bone defect with a new bone, as observed in control animals, in spite of its high osteoin‐ ductive capacity due to its fully interconnected porous structure. To overcome this disadvant‐ age of the IP-CHA implant and to enhance regenerative potential of the implant, rhBMP-2 with its potent bone-inducing capacity in combination with a specific delivery system (carrier material for BMP-2) was added to the surface of the IP-CHA implant. This successfully elicited new bone formation on the surface of the implant and restored normal anatomical surface contour of the iliac bone in 12 weeks using the IP-CHA non-degradable block within the new bone mass. Replacement of the non-biodegradable IP-CHA block by a porous β-TCP implant might have resulted in complete regeneration of the bone defect without remnant biomaterials.

specialized skeletal tissue, such as the vertebral body and load-bearing sites.

MRI will be necessary to determine optimal resection margin of the soft tissue.

rhBMP-2 in humans.

152 New Trends in 3D Printing

Advances in computer-assisted techniques have led to computer-assisted preoperative planning, custom production of surgical implants using patient data, and use of navigation systems in orthopedics. In this study, we accomplished accurate skeletal reconstruction after resection in a virtual iliac bone tumor model in beagle dogs by combining BMP with a 3D printer, CAD, CAM, and a computer navigation system. In future, skeletal reconstruction will become possible for more specialized skeletal tissues, such as the vertebral body and loadbearing sites. Moreover, in future, the development of bioprinting techniques may enable us to reconstruct extensive tissue defects or organ transplantation.
