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.

Antibacterial Mesoporous Titania Films with Embedded Gentamicin and Surface Modified with Bone Morphogenetic Protein 2 to Promote Osseointegration in Bone Implants

“…For MTF coated with hrBMP‐2, with or without gentamicin, the differentiation was more than double the differentiation on bare MTFs. This result was expected as the effectiveness of hrBMP‐2 in promoting preosteoblast differentiation has been demonstrated in a large number of works …”

Improved osseointegration properties of hierarchical microtopographic/nanotopographic coatings fabricated on titanium implants

“…42 Application of the peptides or proteins that induce the osteogenic differentiation could also be an option for optimization of the implant surface. [52][53][54][55] Thus, Gly-Arg-Gly-Asp-Ser peptide on titanium dioxide nanotubes increased MG-63 cell spreading, proliferation, and differentiation. 52…”

The kinetics and mechanism of bone morphogenetic protein 2 release from calcium phosphate‐based implant‐coatings

“…Physically produced CaP‐based layers of metal implants are, for example, manufactured at very high temperatures by plasma spraying; this contrasts the chemically produced layers that are made under near‐physiological (biomimetic) conditions of temperature and of pH, allowing the simultaneous incorporation of osteogenic agents by co‐precipitation, thus conferring them with the additional property of osteoinductivity beside that of osteoconductivity . This supplementary attribute promotes the induction of bone formation by the locally recruited population of osteoprogenitor cells and thus the osseointegration of the implants . Osteogenic agents cannot be incorporated into coatings that are produced at very high temperatures by plasma spraying without rendering them inactive.…”

“…The layers of calcium phosphate that are deposited biomimetically are both biocompatible and biodegradable . It is assumed that the incorporated agent is liberated from the coating during its putative cell‐mediated degradation, and thus would provide a slow and steady release . Such a release kinetic profile is conducive to a sustained neoformation of bone.…”