Lumbar spinal fusion with β-TCP granules and variable Escherichia coli-derived rhBMP-2 dose.
BACKGROUND
The ideal tissue-engineered solution for any bone graft substitute is to assist in the rapid formation of bone and facilitate fusion.


OBJECTIVE
The present study aims to evaluate this E-BMP-2 (Escherichia coli-derived human bone morphogenetic protein-2) in ovine posterolateral lumbar fusion (PLF) to examine the influence of dose and overall performance in a model with similar graft size and diffusive challenges to the human.


METHODS
In vivo large animal model study.


METHODS
An adult ovine PLF was performed in 30 animals with groups of E-BMP-2 with a beta-tricalcium phosphate (β-TCP) carrier at three different dosages, β-TCP alone, and autograft from the iliac crest. The fusions were assessed by radiography (X-ray and microcomputed tomography), mechanical testing, and hard-tissue histology with bone labels at 6, 8, and 10 weeks along with routine paraffin histology at 12 weeks.


RESULTS
Results showed increasing new bone and fusion rate with E-BMP-2 dose, whereas β-TCP alone was largely resorbed and did not achieve fusion in this model at 12 weeks. Autograft showed similar grading for the amount of bone between the transverse processes but a lower fusion rate than β-TCP/E-BMP-2 groups. Bone labels revealed new bone formation at all time points for the E-BMP2 groups, whereas the autograft group showed active bone formation at 10 weeks. Beta-tricalcium phosphate displayed reliable incorporation into the decorticated host bone, whereas limited new bone was found between the transverse processes. At the center of the fusion mass, increased E-BMP-2 dose led to increased incorporation of β-TCP by new bone.


CONCLUSIONS
These results suggest that E-BMP-2 was capable of producing posterolateral fusion in the ovine model that is equal to or superior to autologous graft in terms of fusion rate and mechanical strength. E-BMP-2 dose had considerable influence on β-TCP granule resorption.
Surgical and Orthopaedic Research Laboratories, University of New South Wales, Prince of Wales Clinical School, Level 1 Clinical Sciences Building, Prince of Wales Hospital, Avoca St Randwick, New South Wales 2031, Australia.
Matthew H
MH
Pelletier
Surgical and Orthopaedic Research Laboratories, University of New South Wales, Prince of Wales Clinical School, Level 1 Clinical Sciences Building, Prince of Wales Hospital, Avoca St Randwick, New South Wales 2031, Australia.
Rema A
RA
Oliver
Surgical and Orthopaedic Research Laboratories, University of New South Wales, Prince of Wales Clinical School, Level 1 Clinical Sciences Building, Prince of Wales Hospital, Avoca St Randwick, New South Wales 2031, Australia.
Chris
C
Christou
Surgical and Orthopaedic Research Laboratories, University of New South Wales, Prince of Wales Clinical School, Level 1 Clinical Sciences Building, Prince of Wales Hospital, Avoca St Randwick, New South Wales 2031, Australia.
Yan
Y
Yu
Surgical and Orthopaedic Research Laboratories, University of New South Wales, Prince of Wales Clinical School, Level 1 Clinical Sciences Building, Prince of Wales Hospital, Avoca St Randwick, New South Wales 2031, Australia.
Nicky
N
Bertollo
Osteopharma, Inc., Osteopharma YSK Building 2F, 1-2-5 Uchihommachi Cho-ku Osaka 540-0026, Japan.
Hiroyuki
H
Irie
Surgical and Orthopaedic Research Laboratories, University of New South Wales, Prince of Wales Clinical School, Level 1 Clinical Sciences Building, Prince of Wales Hospital, Avoca St Randwick, New South Wales 2031, Australia. Electronic address: wrwalshau@gmail.com.
William R
WR
Walsh
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D018786:Bone Substitutes / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use*; D004926:Escherichia coli; D008159:Lumbar Vertebrae / Q000601:surgery*; D023421:Models, Animal; D010012:Osteogenesis; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D014182:Transplantation, Autologous
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate
BMP2; Bone graft substitute; Histology; Sheep; Spinal fusion; Tricalcium phosphate