Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model

Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a member of the bone morphogenetic protein family involved in de novo bone induction. Successful use of rhBMP-2 requires implantation with a biomaterial which can act as a scaffold for cell invasion for osteoinduction and retains rhBMP-2 at a site of implantation. This study was carried out to characterize rhBMP-2 pharmacokinetics from a variety of biomaterial carriers in a rat ectopic model. Retention of rhBMP-2 within carriers after 3 h was variable among the carriers (range, 75-10%), with collagenous sponges retaining the highest fraction of implanted dose. A gradual loss of rhBMP-2 was subsequently observed, the kinetics of which was strongly dependent on the implanted carrier. Collagenous carriers were observed to lose rhBMP-2 gradually from the implant site, whereas some of the mineral-based carriers retained a fraction of implanted rhBMP-2 within the implants. These differences in protein pharmacokinetics among carriers, in addition to their physicochemical nature, are expected to affect the biological activity of implanted rhBMP-2.

Parathyroid hormone-related protein (107-111) improves the bone regeneration potential of gelatin–glutaraldehyde biopolymer-coated hydroxyapatite

“…Most proposed release strategies (i.e. using BMP2) provide a burst immediately after the local (surgical) application [41]. However, it is presently debatable whether maintaining the peptide bioactivity and its release burst are equally important factors in this respect.…”

Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

“…Growth factors can be adsorbed or covalently bound to the titanium surface (129,134), but are commonly added to CaP or collagen-coated implants (103,132,(135)(136)(137). Growth factors immobilized on titanium implants pre-coated with collagen or CaP were found to be more effective in inducing bone formation than growth factors bound to untreated titanium surfaces (138)(139)(140). This may be due to a sustained delivery profile or a higher stability of the growth factor (103,141).…”

Electrical stimulation therapies for spinal fusions: current concepts

“…In addition, since the normal physiologic expression of the growth factors is enhanced, treatment with DC stimulation does not have the challenges observed with clinical application of single growth factors which requires implantation of high initial doses to retain the desired effective dose for the therapeutic time period. Short residence time of the applied growth factor, ectopic bone formation, bone resorption, and antibody formation against the single growth factor have been reported following intraoperative applications of single growth factors [16,26,39,40,47,54,66].…”

“…Although carriers have improved delivery and maintenance of the growth factors locally, high initial doses are still needed to achieve the desired mean dose over the therapeutic time period. Growth factors remain locally at the site of application for a short time period, and ectopic bone formation, bone resorption, and antibody formation against the growth factors have been reported [16,26,39,40,47,54,66]. In addition, since this therapeutic approach delivers only a single growth factor, it is still dependent on the recruitment of cells and other growth factors, which have synergistic effects.…”