Stimulation of bone formation with an in situ setting tricalcium phosphate/rhBMP-2 composite in rats

The aim of the study was to determine bone-regenerative effects of an in situ setting tricalcium phosphate (TCP) cement combined with rhBMP-2 and to compare it with autologous bone graft. A trepanation defect of 1.5 mm in the femur diaphysis of Sprague-Dawley rats was filled with an in situ setting TCP cement combined with 0, 0.25, 2.5, or 25 microg of rhBMP-2, an autologous bone graft, or left empty. The rats were euthanized after 1 and 3 weeks and examined by radiography, histology, histomorphometry, and bending tests. All TCP groups with or without BMP-2 showed a good bony ingrowth with a close bone-cement contact. Histomorphometric analysis showed no increase of new bone formation in the defect, but a dose-dependent increase in callus formation with a maximum at 25 microg of rhBMP-2. As shown with intravital fluorochrome staining, new bone formation started earlier using rhBMP-2. Bone strength, measured in a three-point bending test and expressed in percentage of the contralateral healthy femur, was 75% for TCP + 25 microg rhBMP-2, 44% for TCP + 2.5 microg rhBMP-2, and 34% for autologous bone graft. TCP particles were detectable in all groups after 3 weeks. Callus formation and bending strength of the TCP + 25 microg rhBMP-2 group was superior to autologous bone graft. So TCP/rhBMP-2 composites may prove to be an effective substitute for autologous bone grafts.