US EPA

1975128 

Journal Article 

Characterization of absorbable collagen sponges as rhBMP-2 carriers 

Friess, W; Uludag, H; Foskett, S; Biron, R; Sargeant, C 

1999 

Yes 

International Journal of Pharmaceutics
ISSN: 0378-5173
EISSN: 1873-3476 

187 

1 

91-99 

English 

10502616 

10.1016/s0378-5173(99)00174-x 

WOS:000083045300006 

For clinical use recombinant human bone morphogenetic protein (rhBMP-2) is soaked onto an absorbable collagen sponge (ACS) for bone regeneration. Therefore, loss of rhBMP-2 upon mechanical handling during implantation and a potential effect of the carrier on in vivo retention is of interest. The interactions between drug and carrier were looked at from the application mode and the amount of protein which can be mechanically expressed from the combination was investigated. The results indicated that rhBMP-2 binds to the collagen system. The most hydrophilic double extended homodimer showed the least binding affinity to ACS. By extending the waiting time between soaking and implantation, protein incorporation could be increased. In addition, the amount of rhBMP-2 which could be expressed was reduced by heavier ACS material and allowed for a shorter waiting period, especially at lower rhBMP-2 concentration. Crosslinking of ACS with formaldehyde led to reduced binding of rhBMP-2 to collagen either by direct hindrance of binding or reduction in swelling and number of binding sites available. Higher product pH or anion concentration enabled to increase rhBMP-2 incorporation but was limited by the potential precipitation of rhBMP-2. Despite a variety of chemical changes of ACS by ethylene oxide sterilization incorporation was not changed significantly. The in vivo release kinetics of 125I-rhBMP-2 from the collagen sponge were studied using a rat ectopic implant model. The ACS/rhBMP-2 systems tested demonstrated small, but significant differences in the in vivo retention of rhBMP-2. Consequently, it is important to have as little variability in pH, anion concentration, crosslinking and ACS mass as possible to achieve consistent or maximum binding and to avoid rhBMP-2 precipitation. Furthermore, these characteristics can be important for other in vivo applications. 

collagen; bone morphogenetic protein; sterilization; crosslinking