Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Abstract

<jats:p content-type="fine-print"><jats:italic>Object.</jats:italic> Growth factors such as bone morphogenetic protein—2 (BMP-2) have been proven to promote spine fusion and to overcome the disadvantages of an autologous bone graft. The optimum method to deliver such growth factors remains a matter of discussion. The purpose of this study was to determine the safety and efficacy of a new poly(<jats:sc>d,l</jats:sc>-lactide) (PDLLA) carrier system for BMP-2 and to compare this carrier system with a collagen sponge carrier in a sheep cervical spine interbody fusion model.</jats:p> <jats:p content-type="fine-print"><jats:italic>Methods.</jats:italic> Thirty-two sheep underwent C3–4 discectomy and fusion: Group 1, titanium cage (eight animals); Group 2, titanium cage coated with a PDLLA carrier (eight animals); Group 3, titanium cage coated with a PDLLA carrier including BMP-2 (150 µg) (eight animals); and Group 4, titanium cage combined with a collagen sponge carrier including BMP-2 (150 µg) (eight animals). Blood samples, body weight, and temperature were assessed. Radiographs were obtained pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After the sheep were killed 12 weeks postoperatively, flexion—extension radiography was performed to evaluate fusion sites. Quantitative computerized tomography scans were obtained to assess bone mineral density (BMD), bone mineral content (BMC), and bone callus volume (BCV). Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending. Stiffness, range of motion, neutral, and elastic zone were determined. Histomorphological and -morphometrical analyses were performed, and polychrome sequential labeling was used to determine the timeframe of new bone formation.</jats:p> <jats:p content-type="fine-print">There were no differences among the groups concerning blood counts, body weight, and temperature. Compared with the noncoated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus, as well as slightly higher values for BMC, BCV, and the bone volume/total volume ratio. In comparison with the cage-alone group, the BMP-2 groups showed significantly higher values for BMD and biomechanical stiffness. Histomorphological, -morphometrical, and polychrome sequential labeling analyses demonstrated greater progression of callus formation in the BMP-2 groups than in any other group. Compared with BMP-2 delivered using a collagen sponge carrier, BMP-2 application with a PDLLA carrier resulted in a higher BCV and a greater progression of interbody callus formation in the histomorphometrical analysis.</jats:p> <jats:p content-type="fine-print"><jats:italic>Conclusions.</jats:italic> The use of cervical spine interbody fusion cages coated with PDLLA as a delivery system for growth factors was effective. In this 12-week follow-up study, the PDLLA coating showed no adverse effects. The slight but not significant positive effect of the PDLLA carrier on interbody fusion might be a result of the degradation process of the biodegradable carrier. Compared with collagen sponge delivery of BMP-2, the PDLLA-coated interbody cages significantly increased the results of interbody bone matrix formation. In this new combination (implant + PDLLA + growth factor) the cage represents a “real fusion” cage, because it not only serves as a mechanical device for spinal fixation but also as a local drug delivery system.</jats:p>

High Rate of Fusion in Sheep Cervical Spines Following Anterior Interbody Surgery With Absorbable and Nonabsorbable Implant Devices

“…32 Kandziora et al reported 0 of 8 solid fusions using tricortical iliac crest bone graft, 1 of 8 using Harm's titanium mesh cages, and 0 of 8 using titanium box cages in sheep cervical spines (C3-C4) after 12 weeks. 36 Similar results were reported from the same laboratory using absorbable polymercoated titanium cages, 33,37 and complete fusions could only be demonstrated with the use of growth factors. 37 This group also reported 0 of 8 solid fusions with tricortical iliac crest graft, 0 of 7 with an absorbable 70:30 poly(L-lactide:D,L-lactide) copolymer cage, and 6 of 8 with an absorbable polymer-calcium phosphatecomposite (PCC) cage all stabilized with titanium plates.…”

32k Da protein improve ovariectomy-induced bone loss in rats

“…A marked atrophy of the uterus has been used as evidence of the success of ovariectomy for estrogen directly affects uterine weight. 10 Indeed, ovariectomy resulted in a significant decrease in uterine weight. Ironically, 32KP did not exhibit any uterotrophic activity; this lack of uterotrophic activity could be beneficial in reducing the risk of diseases associated with E2 treatment.…”

Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion

“…19 The Food and Drug Administration has approved the use of a type-I collagen sponge enhanced with rhBMP-2 in combination with a tapered, threaded fusion cage (LT-CAGE; Medtronic Sofamor Danek) for the treatment of lumbar degenerative disc disease. 20 Although less attention has been focused on the use of rhBMP-2 in anterior cervical spine fusions, both animal [21][22][23] and human 24 studies have shown favorable outcomes. The primary feature was the ability of rhBMP-2 to enhance significantly the rate of fusion without associated adverse effects.…”