Regenerative repair of bone defects with osteoinductive hydroxyapatite fabricated to match the defect and implanted with combined use of computer-aided design, computer-aided manufacturing, and computer-assisted surgery systems: a feasibility study in a canine model

Currently, regenerative repair of large bone defects that result from bone tumor resection or severe trauma is a challenging issue because of the limited regenerative potential of bone and treatment modalities. The aim of this study was to achieve repair of large bone defects to the original three-dimensional (3D) anatomical state by combining computer-aided technologies and local delivery of bone morphogenetic protein (BMP) in a canine model. Computed tomography (CT) images of the pelvic bone of each dog were obtained, and an imaginary spherical malignant bone tumor of 15-mm diameter was placed in the left ilium of a canine on the 3D CT image. Resection of the whole tumor with a 10-mm margin of healthy bone was planned preoperatively by using computer-aided design (CAD) software. In addition, an image of the implant to be used to fill the resulting bone defect was constructed on the computer image. A porous hydroxyapatite (HA) implant identical to the imaged bone defect was made by shaving a tetragonal porous apatite block (40 x 20 x 10 mm) with a computer-aided manufacturing system operated by using the CT-image data of the bone defect obtained from the CAD system. To resect the iliac bone as planned preoperatively on the 3D CT image, computer-aided surgery was performed using the CT data. The defect was filled with the HA implant fabricated as described and coated with a putty carrier either with BMP-2 (BMP group, n = 6) or without BMP-2 (control group, n = 6). In the BMP group, new bone formation was noted around each implant on CT images at 3 weeks after surgery and was remodeled to restore the original anatomy of the ilium on serial CT images. At 12 weeks, the implant was enclosed within new bone, and histological analysis revealed bone formation on and within the implant. Little bone formation was noted in the control group. This new method may enable efficacious and precise regenerative repair of large bone defects without bone grafting.