The optimal carrier for BMP-2: a comparison of collagen versus fibrin matrix.
BACKGROUND
The aim of our study was to investigate in vitro and in a new in vivo rat model for impaired bone healing whether a low dose BMP-2 preparation in fibrin would be equivalent or better than the combination of collagen and a high dose of BMP-2 which is currently in clinical use.


METHODS
In a 14 day period we compared the in vitro release kinetics of an absorbable collagen sponge (ACS) with 72 μg rhBMP-2 in the BMPC group and fibrin matrix with 10 μg rhBMP-2 in the BMPF group. In our in vivo experiment a critical sized osteotomy was performed in the rat femur, which was filled with a spacer, inhibiting bone formation for a period of 4 weeks. In a second operation this spacer was removed and the test item was applied into the defect. We compared the BMPF and BMPC groups with the ACS alone, FIBRIN alone and the EMPTY (4w/8w) control groups. 4 and 8 weeks after the second operation, specimens were analysed by X-ray and μCT imaging. Mechanically stable femurs were biomechanically evaluated.


RESULTS
Cumulative BMP-2 release was five times higher in the BMPF group than in the BMPC group during the observation period. μCT analysis revealed that both the extent of bone union and the bone volume were significantly higher in the group with a lower dose of BMP-2 in fibrin matrix than in the groups without BMP-2 treatment. However there was no statistically significant difference between the BMPF and BMPC groups.


CONCLUSIONS
We conclude that fibrin matrix is an excellent carrier for BMP-2 and that it provides equivalent results with a sevenfold lower dose of BMP-2 compared with ACS.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Donaueschingenstrasse 13, 1200, Vienna, Austria. sebastian.schuetzenberger@gmail.com
Sebastian
S
Schützenberger
Arthur
A
Schultz
Thomas
T
Hausner
Rudolf
R
Hopf
Gerald
G
Zanoni
Tatjana
T
Morton
Karl
K
Kropik
Martijn
M
van Griensven
Heinz
H
Redl
D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D003094:Collagen / Q000494:pharmacology*; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D005337:Fibrin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010027:Osteotomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D005337:Fibrin; D003094:Collagen