title: Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis model.
abstract: The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to two calcium-based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP-2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP-2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera. Differences observed between the two materials for the area under the retention vs. time profile (AUC; 988%*day for BCP vs. 1070%*day for BCP/ACS, p = 0.57) and the mean residence time (MRT; 10.2 days for BCP vs. 7.6 days for BCP/ACS, p = 0.06) were not statistically significant. Initial retention/incorporation of rhBMP-2 was slightly higher for rhBMP-2/BCP/ACS than for rhBMP-2/BCP (96.8% vs. 86.0%, p < 0.05). Animals receiving rhBMP-2/BCP showed a longer terminal retention half-life (t1/2) than did those receiving rhBMP-2/BCP/ACS (7.5 vs. 4.5 days, p < 0.05). The urinary radioactivity recovery data supported the data obtained by scintigraphy. Over the 36 day collection period, essentially complete recovery of radioactivity (dose) in urine was observed for rhBMP-2/BCP and rhBMP-2/BCP/ACS and the majority of the radioactivity (approximately 95%) was soluble in trichloroacetic acid, suggesting extensive catabolism of rhBMP-2 before renal excretion. Fecal recovery of radioactivity was low, approximately 2-3%. In conclusion, rhBMP-2 was retained at the implant site when delivered with either BCP or BCP/ACS based on mean residence time and area under the retention curve vs. time profile. Use of these matrices resulted in detectable rhBMP-2 levels at the surgical site for over a week in contrast to data reported with several other matrices that lasted less time. Systemic catabolism and elimination of the rhBMP-2 was extensive and systemic presence of the protein was negligible.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Emory University, Altanta, GA 30322, USA.
authors.forename: John
authors.initials: J
authors.lastname: Louis-Ugbo
authors.forename: Hak-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boden
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Mayr
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Li
authors.forename: Howard
authors.initials: H
authors.lastname: Seeherman
authors.forename: Darren
authors.initials: D
authors.lastname: D'Augusta
authors.forename: Cara
authors.initials: C
authors.lastname: Blake
authors.forename: Aiping
authors.initials: A
authors.lastname: Jiao
authors.forename: Steve
authors.initials: S
authors.lastname: Peckham
mesh_terms: D000818:Animals; D019540:Area Under Curve; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000493:pharmacokinetics*; D018786:Bone Substitutes / Q000378:metabolism; D002130:Calcium Phosphates / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004337:Drug Carriers / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism / Q000601:surgery; D023421:Models, Animal; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485828:alpha-tricalcium phosphate; C499469:recombinant human bone morphogenetic protein-2; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; D003094:Collagen; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous