A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats.
BACKGROUND
Recombinant bone morphogenetic proteins (rhBMPs) have been used successfully in clinical trials. However, large doses of rhBMPs were required to induce adequate bone repair. Collagen sponges (CSs) have failed to allow a more sustained release of rhBMPs. Ongoing research aims to design carriers that allow a more controlled and sustained release of the protein. E-Matrix is a injectable scaffold matrix that may enhance rhBMP activity and stimulate bone regeneration.


OBJECTIVE
The purpose of this study was to test E-Matrix as a carrier for rhBMPs in a CS and examine its feasibility in clinical applications by using a rat spinal fusion model.


METHODS
A total of 80 Lewis rats aged 8-16 weeks were divided into nine groups.


METHODS
Rat spinal fusion model.


METHODS
Radiographs were obtained at 4, 6, and 8 weeks. The rats were sacrificed and their spines were explanted and assessed by manual palpation, high-resolution microcomputed tomography (micro-CT), and histologic analysis.


METHODS
Group I animals were implanted with CS alone (negative control); Group II animals with CS containing 10microg rhBMP-2 (positive control); Group III animals with CS containing 3microg rhBMP-2; Group IV animals with CS containing 3microg rhBMP-2 and E-Matrix; Group V animals with CS containing 1microg rhBMP-2; Group VI animals with CS containing 1microg rhBMP-2 and E-Matrix; Group VII animals with CS containing 0.5microg rhBMP-2; Group VIII animals with CS containing 0.5microg rhBMP-2 and E-Matrix; and Group IX animals with CS and E-Matrix without rhBMP-2.


RESULTS
Radiographic evaluation, micro-CT, and manual palpation revealed spinal fusion in all rats in the BMP-2 and E-Matrix groups (IV, VI, and VIII) and high-dose BMP-2 groups (II and III). Four spines in the 3microg rhBMP-2 group (V) fused, and one spine in the 0.5microg rhBMP-2 group (VII) exhibited fusion. No spines were fused in Groups I (CS alone) and IX (E-Matrix alone). The volume of new bone in the area between the tip of the L4 transverse process and the base of the L5 transverse process in Group IV was equivalent to the volumes observed in Group II.


CONCLUSIONS
E-matrix enhances spinal fusion as a carrier for rhBMP-2 in a rat spinal fusion model. The results of this study suggest that E-Matrix as a growth factor carrier may be applicable to spinal fusion and may improve rhBMP-2's activity at the fusion site.
Miyazaki
Masashi
M
Department of Orthopaedic Surgery, Oita University, Oita, Japan.
Morishita
Yuichiro
Y
He
Wubing
W
Hu
Ming
M
Sintuu
Chananit
C
Hymanson
Henry J
HJ
Falakassa
Jonathan
J
Tsumura
Hiroshi
H
Wang
Jeffrey C
JC
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects; D003094:Collagen / Q000627:therapeutic use*; D006801:Humans; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013123:Spinal Fusion / Q000379:methods*; D013552:Swine; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D055114:X-Ray Microtomography
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen