Posterolateral lumbar fusion using Escherichia coli–derived rhBMP-2/hydroxyapatite in the mini pig

• Published in: The spine journal Vol. 14; no. 12; pp. 2959 - 2967
• Main Authors: Kong, Chang-Bae, Lee, Jae Hyup, Baek, Hae-Ri, Lee, Choon-Ki, Chang, Bong-Soon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2014
• Subjects: Animals; Bone Morphogenetic Protein 2 - administration & dosage; Bone Morphogenetic Protein 2 - therapeutic use; Bone Transplantation - methods; Drug Carriers - chemistry; Durapatite - chemistry; Escherichia coli–derived rhBMP-2; Humans; Hydroxyapatite; Lumbar Vertebrae - surgery; Male; Mini pig; Orthopedics; Osteoinductivity; Posterolateral fusion; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Spinal Fusion - methods; Swine; Swine, Miniature; Transforming Growth Factor beta - administration & dosage; Transforming Growth Factor beta - therapeutic use; Mini pig; Posterolateral fusion; Hydroxyapatite; Escherichia coli–derived rhBMP-2; Osteoinductivity
• ISSN: 1529-9430; 1878-1632; 1878-1632
• DOI: 10.1016/j.spinee.2014.06.007

Hydroxyapatite (HA) is used as a bone graft extender for posterolateral spinal fusion in human. It is also useful as a recombinant human bone morphogenetic protein (rhBMP)-2 carrier because of its high affinity for rhBMP-2. To assess the osteoinductivity of Escherichia coli–derived rhBMP-2 (E-BMP-2) using HA granules as a carrier and to evaluate the bone-forming ability depending on the different dosages of E-BMP-2. A mini-pig lumbar posterolateral fusion model using microcomputed tomography (μCT) scanning. Thirty-one adult male mini pigs were randomized into a single control group (n=8) without E-BMP-2 and two experimental groups with two different doses of E-BMP-2 (1 mg per side, n=8 and 3 mg per side, n=15). Outcome was measured by plain radiography, manual palpation, CT, three-dimensional μCT, and histologic examinations. Bilateral intertransverse process arthrodesis was performed, and E-BMP-2 (0, 1.0, 3.0 mg per side) was implanted into the intertransverse space using HA granules as a carrier. Three mini pigs were removed because of death. Among 28 experimental subjects, 19 animals achieved solid bony union. The fusion rates were 37.5% for control group, 71.4% for 1 mg group, and 84.6% for 3 mg group. Fusion rates were significantly different among groups (p=.031). However, there was no statistically significant difference in fusion rates between 1 and 3 mg groups (p=.587). Thirty-eight intertransverse fusion masses of 19 subjects underwent μCT scanning. The bone volumes determined by μCT were 12,603±3,240 mm3 for control group, 18,718±3,000 mm3 for 1 mg group, and 26,768±7,256 mm3 for 3 mg group, and the difference between groups was statistically significant (p<.001). This study shows that E-BMP-2 has osteoinductive activity in dose-dependent fashion, and porous HA granule is suitable for E-BMP-2 carrier in a porcine posterolateral fusion model. These preliminary findings suggest that E-BMP-2–adsorbed porous HA granules could be a novel effective bone graft substitute.