Biocoating of implants with rhBMP-2

Previously it has been shown that recombinant human bone morphogenetic protein (rhBMP-2) can be chemically immobilized by "anchor molecules" on titanium surfaces for serving as a drug delivery device. This opened the question of whether the insoluble immobilized rhBMP-2 retains its activity in comparison to the same amount of soluble rhBMP-2 included with the implant samples. Small electropolished titanium miniplates (10x6x0.8 mm) were "surface-enhanced" by a novel treatment with chromosulfuric acid and then coated with a total amount of 150-200 ng rhBMP-2 prepared by recombinant technology. Periosteal flaps (7x20 mm) were detached and isolated from the anterior surface of the tibiae of adult rabbits and wrapped around the titanium sample plates which were then implanted in the M. gastrocnemius. In the first group (=8) the rhBMP-2 coated titanium plate was wrapped in the periosteum and implanted in the muscle. In the second group (rc=8) 1 ug soluble rhBMP-2 was injected between the uncoated implant and the periosteum. In the third group unmodified plates served as controls. Animals were sacrificed after 28 days and a quantitative evaluation was carried out by means of serial sections. Untreated plates showed bone formation in 2/12 implants, rhBMP-2 coated implants in 6/8 and implants with rhBMP-2 administered subperiostally in 8/8 cases. In plates with rhBMP-2 immobilized on the surface the induced bone had direct contact to the implant in all cases while in the group with free administered rhBMP-2 the bone had no contact to the implant in two cases. Bone volume, bone surface area, and trabecular number displayed no difference between the two rhBMP-2-groups. However, in the biocoated group a tendency to an increase in the bone-implant contact area was evident. No differences in osteoid area, osteoid perimeter and eroded perimeter were detected. We conclude that in the case of non-immobilized rhBMP-2 there is the danger for formation of fibrous tissue between the implant and the newly formed bond and in addition the generation of ectopic bone at inappropriate places. In contrast chemically immobilized rhBMP-2 does not have these drawbacks and at the same time displays a biological activity surfaces similar to that of soluble rhBMP-2 demonstrating that biomaterial surfaces can be tailored for a selective and specific interaction with the target tissue.