title: Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model.
abstract: In clinical orthopaedics, total joint replacements and spinal fusions are routine undertakings. Many of the implicated patients suffer from osteoporosis, severe arthrosis or osteopaenia. In individuals thus afflicted, the bony bed lacks the mechanical stability that is a requisite for a firm anchorage of the implant and its functional competence. To promote the bony bondage of an implant it is necessary to induce neo-ossification by the introduction of an osteogenic agent, such as bone morphogenetic protein 2 (BMP-2). Since this growth factor is generally applied in a free form and at high dosages to maximise its osteogenicity, untoward side effects frequently ensue. We hypothesise that the administration of BMP-2 using a suitable delivery vehicle, and its gradual, low dose release therefrom in a cell-mediated manner, would avert the triggering of undesired side effects and enhance its efficacy. To test this postulate, implants of porous titanium were coated with a layer of calcium phosphate into which BMP-2 was biomimetically incorporated at dosages ranging from 0.8 to 500 µg/g of coating material (delivery system) prior to their surgical placement in the tibiae of adult sheep. The volume and the surface area of newly-formed bone were evaluated histomorphometrically after 3 and 6 weeks. The highest values were achieved using BMP-2 dosages of 20 to 100 µg/g of coating: The deposition of bone was confined to the immediate vicinity of the implant and was observed deep within the interstices of its meshwork, to the walls of which it bonded well. The findings of the study attest to the validity of our hypothesis.
authors.affiliation: Departments of Osteoporosis and Orthopaedic Surgery, Inselspital (DKF), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland.nahoko.shintani@dkf.unibe.ch.
authors.forename: E B
authors.initials: EB
authors.lastname: Hunziker
authors.forename: J
authors.initials: J
authors.lastname: Jovanovic
authors.forename: A
authors.initials: A
authors.lastname: Horner
authors.forename: M J
authors.initials: MJ
authors.lastname: Keel
authors.forename: K
authors.initials: K
authors.lastname: Lippuner
authors.forename: N
authors.initials: N
authors.lastname: Shintani
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D000071556:Cancellous Bone / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D021621:Imaging, Three-Dimensional; D020007:Implants, Experimental; D007700:Kinetics; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D016348:Osseointegration / Q000187:drug effects*; D016062:Porosity; D012756:Sheep; D013997:Time Factors; D014025:Titanium / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D014025:Titanium