title: Osseointegration: the slow delivery of BMP-2 enhances osteoinductivity.
abstract: Although the placement of dental and orthopedic implants is now generally a safe, reliable and successful undertaking, the functional outcome is less assured in patients whose bone-healing capacity is compromised. To enhance peri-implant osteogenesis in these individuals, BMP-2 could be locally administered. However, neither a free suspension nor an implant-adsorbed depot of the agent is capable of triggering sustained bone formation. We hypothesize that this end could be achieved by incorporating BMP-2 into the three-dimensional crystalline latticework of a bone-mineral like, calcium-phosphate implant coating, where from it would be liberated gradually - as the inorganic layer undergoes osteoclast-mediated degradation - not rapidly, as from an implant-adsorbed (two-dimensional) depot. To test this postulate, we compared the osteoinductive efficacies of implant coatings bearing either an incorporated, an adorbed, or an incorporated and an adsorbed depot of BMP-2 at a maxillary site in miniature pigs. The implants were retrieved 1, 2 and 3 weeks after surgery for the histomorphometric analysis of bone formation within a defined 'osteoinductive' space. At each juncture, the volume of newly-formed bone within the osteoinductive space was greatest around implants that bore a coating-incorporated depot of BMP-2, peak osteogenic activity being attained during the first week and sustained thereafter. In the other groups, the temporal course of bone formation was variable, and the peak levels were not sustained. The findings of this study confirm our hypothesis: they demonstrate that we now have at our disposal a means of efficaciously augmenting and expediting peri-implant bone formation. Clinically, this possibility would render the process of implant placement a safer and a more reliable undertaking in patients whose bone-healing capacity is compromised, and would also permit a curtailment of the postoperative recovery period by a forestallment of the mechanical-loading phase.
authors.affiliation: Center of Regenerative Medicine for Skeletal Tissues, Department of Orthopaedic Surgery and Clinical Research, University of Bern, Switzerland. ernst.hunziker@dkf.unibe.ch
authors.forename: E B
authors.initials: EB
authors.lastname: Hunziker
authors.forename: L
authors.initials: L
authors.lastname: Enggist
authors.forename: A
authors.initials: A
authors.lastname: Küffer
authors.forename: D
authors.initials: D
authors.lastname: Buser
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000737:chemistry; D015921:Dental Implants; D016348:Osseointegration / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D013552:Swine; D013556:Swine, Miniature
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D015921:Dental Implants; C020243:calcium phosphate