Bone formation in Transforming Growth Factor beta-I-loaded titanium fiber mesh implants

The osteoconductive properties of porous titanium (Ti) fiber mesh with or without a calcium phosphate (Ca-P) coating and osteoinductive properties of non-coated Ti fiber mesh loaded with recombinant human Transforming Growth Factor beta-1 (rhTGF-beta(1)) were investigated in a rabbit non-critical size cranial defect model. Nine Ca-P-coated and 18 non-coated porous titanium implants, half of them loaded with rhTGF-beta(1), were bilaterally placed in the cranium of 18 New Zealand White rabbits. At 8 weeks postoperative, the rabbits were sacrificed and the skulls with the implants were retrieved. Histological analysis demonstrated that in the TGF-beta(1)-loaded implants, bone had been formed throughout the implant, up to its center, whereas in the non-loaded implants only partial ingrowth of bone was observed. Bone formation had a trabecular appearance together with bone marrow-like tissue. No difference in ingrowth could be observed between the non-TGF-beta(1)-loaded non-coated implants and the Ca-P-coated ones. All histological findings were confirmed by image analysis: 97% ingrowth was seen in the rhTGF-beta(1)-loaded implants, while only 57% and 54% ingrowth was observed in the non-loaded Ca-P-coated and non-coated implants, respectively. Bone surface area and bone fill were significantly higher in the rhTGF-beta(1)-loaded implants (1.37 mm(2) and 36%, respectively) than in the non-loaded implants (0.57 mm(2) and 26%). No statistical difference was found for any parameter between the Ca-P-coated and noncoated implants. Quadruple fluorochrome labeling showed that in the Ti and Ti-CaP implants mainly bone guidance had occurred from the former defect edge, while in the Ti-TGF-beta(1) implants bone formation had mainly started in the center of a pore and proceeded in a centrifugal manner. Our results show that: (1) the combination of Timesh with TGF-beta can induce orthotopic bone formation; (2) Ti-fiber mesh has good osteoconductive properties; (3) a thin Ca-P coating, as applied in this study, does not seem to further enhance the bone-conducting properties of a titanium scaffold material.