Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model

Background: The objective of this study was to evaluate local bone formation at titanium porous oxide (TPO) implant surfaces adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2). Methods: In vitro studies were used to estimate the kinetics of I-125-labeled rhBMP-2 released from TPO surfaces with narrow (N) or open (O) pores. Machined/turned titanium (MT) surfaces served as control. The rat ectopic model was used to assess local bone formation. Briefly, TPO-N, TPO-O, and MT disc implants adsorbed with 5, 10, or 20 mu g rhBMP-2, respectively, were implanted subcutaneously into the ventral thoracic region in 5-week-old male Long Evans rats. The animals were euthanized at day 14 postsurgery when implants with surrounding tissues were removed, radiographed, and gross observations recorded. The specimens were processed for histologic evaluation using conventional cut-and-grind techniques. TPO implants without rhBMP-2 included in a preliminary evaluation revealed no evidence of bone formation, tissue encapsulation, or vascularity, thus such controls were not further used. Results: TPO and MT implant surfaces adsorbed with 5 mu g rhBMP-2 retained 2.3-5.4% rhBMP-2 following immersion and rinse in buffer, and 1.1-2.2% rhBMP-2 following repeated immersions and rinses over 27 days. TPO implants retained the most rhBMP-2 and MT implants retained the least. Explants revealed increased hard tissue formation, tissue encapsulation, and vascularity at TPO compared with MT implants. Radiographic observations were consistent with the explant observations. The histologic analysis showed greater amounts of bone formation, osteoblastic cells, osteoid, marrow, tissue encapsulation, vascularity, and bone voids for implants adsorbed with 10 and 20 mu g rhBMP-2, and for TPO implants at the 5-mu g rhBMP-2 dose. The histometric analysis revealed significantly greater bone formation at TPO-O than at MT implants at the 5-mu g rhBMP-2 dose. All surfaces showed significant bone formation at the 10- and 20-mu g dose. Conclusions: rhBMP-2 adsorbed onto TPO implant surfaces executes an osteoinductive effect including bone contacting the implant surface. This effect is surface- and dose-dependent; the TPO-O surface yielding the most bone at the low discriminating rhBMP-2 dose.