[Experimental fusion of the sheep cervical spine. Part II: Effect of growth factors and carrier systems on interbody fusion].
BACKGROUND
A sheep cervical spine interbody fusion model was used to determine the effect of different carriers and growth factors on interbody bone matrix formation. The purpose of this study was to compare the efficacy and safety of combined IGF-I and TGF-beta1 application with BMP-2 application in spinal fusion. Additionally, a new poly (D, L-lactide) carrier system was compared to a collagen sponge carrier.


METHODS
Forty sheep underwent C3/4 discectomy and fusion: group 1: titanium cage ( n=8), group 2: titanium cage coated with a PDLLA carrier (n=8), group 3: titanium cage coated with a PDLLA carrier including BMP-2 ( n=8), group 4: titanium cage with a collagen carrier including BMP-2 ( n=8), and group 5: titanium cage coated with a PDLLA carrier including IGF-I and TGF-beta1 ( n=8). Blood samples, body weight, and temperature were analyzed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, disc space height (DSH) and intervertebral angle (IVA) were measured. After 12 weeks the animals were killed and fusion sites were evaluated using functional radiographic views in flexion and extension. Quantitative computed tomographic scans (QCT) were performed to assess bone mineral density (BMD), bone mineral content (BMC), and bony callus volume (BCV). Biomechanical testing was carried out in flexion, extension, axial rotation, and lateral bending. Range of motion (ROM), neutral zone (NZ), and elastic zone (EZ) were determined. Histomorphological and histomorphometrical analyses were performed and polychrome sequential labeling was used to determine the time frame of new bone formation.


RESULTS
In comparison to the non-coated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus and bone volume/total volume ratio. In comparison to the cage groups (groups 1 and 2), the cage plus BMP-2 (groups 3 and 4) and the cage plus IGF-I and TGF-beta1 group (group 5) demonstrated a significantly higher fusion rate in radiographic findings, a higher biomechanical stability, an advanced interbody fusion in histomorphometric analysis, and an accelerated interbody fusion on fluorochrome sequence labeling. BMP-2 application by the PDLLA carrier system (group 3) demonstrated significantly higher bony callus volume than BMP-2 application by a collagen sponge carrier (group 4). The BMP-2 group (group 3) showed significantly lower residual motion on functional radiographic evaluation and higher intervertebral bone matrix formation on fluorochrome sequence labeling at 9 weeks in comparison to the IGF-I/TGF-beta1 group (group 5). In contrast, the IGF-I/TGF-beta1 group (group 5) showed a significantly higher bone mineral density of the callus than the BMP-2 group (group 3).


CONCLUSIONS
PDLLA coating of cervical spine interbody fusion cages as a delivery system for growth factors was effective and safe. In comparison to the collagen sponge carrier, the new PDLLA carrier system was able to improve results of interbody bone matrix formation. Both growth factors (BMP-2 and combined IGF-I and TGF-beta1) significantly accelerated results of interbody fusion. Based on these preliminary results, the combined IGF-I/TGF-beta1 application yields results equivalent to BMP-2 application at an early time in anterior sheep cervical spine fusion.
Kandziora
F
F
Unfall und Wiederherstellungschirurgie, Universitätsklinikum Charité der Humboldt-Universität Berlin, Campus Virchow-Klinikum, Germany. frank.kandziora@charite.de
Scholz
M
M
Pflugmacher
R
R
Krummrey
G
G
Schollmeier
G
G
Schmidmaier
G
G
Schnake
K J
KJ
Duda
G
G
Raschke
M
M
Haas
N P
NP
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001857:Bone Matrix / Q000187:drug effects* / Q000473:pathology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002574:Cervical Vertebrae / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D020099:Coated Materials, Biocompatible; D003094:Collagen; D004337:Drug Carriers; D004548:Elasticity; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011091:Polyesters; D019736:Prostheses and Implants; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D011091:Polyesters; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I; D003094:Collagen