Implantation of recombinant human bone morphogenetic proteins with biomaterial carriers: A correlation between protein pharmacokinetics and osteoinduction in the rat ectopic model
✍ Scribed by Uludag, Hasan ;D'Augusta, Darren ;Golden, Janet ;Li, Jian ;Timony, Greg ;Riedel, Rod ;Wozney, John M.
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 357 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0021-9304
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✦ Synopsis
This study was carried out to determine the effect of recombinant human bone morphogenetic protein (rhBMP) pharmacokinetics (PK) on rhBMP-induced osteoinductive activity. It was our working hypothesis that the PK of a rhBMP significantly affects its osteoinductive activity. The PK of various rhBMPs (rhBMP-2, rhBMP-4, rhBMP-6, and chemically modified rhBMP-2) implanted with four biomaterial carries (Helistat, hDBM, Osteograf/N, and Dexon) was determined using 125 I-labeled proteins in the rat ectopic assay. A select combination of rhBMP and carriers then was evaluated in the rat ectopic assay for osteoinductive activity using a semi-quantitative histologic scoring system. The results indicate that initial protein retention is dependent on protein isoelectric point (pI); proteins with a higher pI yielded a higher implant retention. Subsequent PK was not strongly dependent on the pI or on the carrier.
Because of the difference in early retention, the rhBMPcarrier combinations exhibited a >100-fold difference in implant-retained protein dose. When rhBMP-2 and rhBMP-4 were implanted with the carriers, more rhBMP-2 was retained in an implant, and the osteoinductive potency of rhBMP-2 typically was higher than rhBMP-4 at low implantation doses. We conclude that protein pI plays a significant role in the local retention of implanted rhBMP and that higher retention yields a higher osteoinductive activity.