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1.  Genetically Modified Mesenchymal Stem Cells Induce Mechanically Stable Posterior Spine Fusion 
Tissue Engineering. Part A  2010;16(12):3679-3686.
Most spine fusion procedures involve the use of prosthetic fixation devices combined with autologous bone grafts rather than biological treatment. We had shown that spine fusion could be achieved by injection of bone morphogenetic protein-2 (BMP-2)-expressing mesenchymal stem cells (MSCs) into the paraspinal muscle. In this study, we hypothesized that posterior spinal fusion achieved using genetically modified MSCs would be mechanically comparable to that realized using a mechanical fixation. BMP-2-expressing MSCs were injected bilaterally into paravertebral muscles of the mouse lumbar spine. In one control group BMP-2 expression was inhibited. Microcomputed tomography and histological analyses were used to evaluate bone formation. For comparison, a group of mouse spines were bilaterally fused with stainless steel pins. The harvested spines were later tested using a custom four-point bending apparatus and structural bending stiffness was estimated. To assess the degree to which MSC vertebral fusion was targeted and to quantify the effects of fusion on adjacent spinal segments, images of the loaded spine curvature were analyzed to extract rigidity of the individual spinal segments. Bone bridging of the targeted vertebrae was observed in the BMP-2-expressing MSC group, whereas no bone formation was noted in any control group. The biomechanical tests showed that MSC-mediated spinal fusion was as effective as stainless steel pin-based fusion and significantly more rigid than the control groups. Local analysis showed that the distribution of stiffness in the MSC-based fusion group was similar to that in the steel pin fusion group, with the majority of spinal stiffness contributed by the targeted fusion at L3–L5. Our findings demonstrate that MSC-induced spinal fusion can convey biomechanical rigidity to a targeted segment that is comparable to that achieved using an instrumental fixation.
doi:10.1089/ten.tea.2009.0786
PMCID: PMC2991214  PMID: 20618082
2.  A comparison of commercially available demineralized bone matrix for spinal fusion 
European Spine Journal  2007;16(8):1233-1240.
In an effort to augment the available grafting material as well as to increase spinal fusion rates, the utilization of a demineralized bone matrix (DBM) as a graft extender or replacement is common. There are several commercially available DBM substances available for use in spinal surgery, each with different amounts of DBM containing osteoinductive proteins. Each product may have different osteoinductivity potential due to different methods of preparation, storage, and donor specifications. The purpose of this study is to prospectively compare the osteoinductive potential of three different commercially available DBM substances in an athymic rodent spinal fusion model and to discuss the reasons of the variability in osteoinductivity. A posterolateral fusion was performed in 72 mature athymic nude female rats. Three groups of 18 rats were implanted with 1 of 3 DBMs (Osteofil, Grafton, and Dynagraft). A fourth group was implanted with rodent autogenous iliac crest bone graft. The rats were sacrificed at 2, 4, 6, and 8 weeks. A dose of 0.3 cm3 per side (0.6 cm3per animal) was used for each substance. Radiographs were taken at 2 weeks intervals until sacrifice. Fusion was determined by radiographs, manual palpation, and histological analysis. The Osteofil substance had the highest overall fusion rate (14/18), and the highest early 4 weeks fusion rate of (4/5). Grafton produced slightly lower fusion rates of (11/17) overall, and lower early 4 weeks fusion rate of (2/5). There was no statistically significant difference between the rate of fusion after implantation of Osteofil and Grafton. None of the sites implanted with Dynagraft fused at any time point (0/17), and there was a significantly lower fusion rate between the Dynagraft and the other two substances at the six-week-time point and for final fusion rate (P = 0.0001, Fischer’s exact test). None of the autogenous iliac crest animals fused at any time point. Non-decalcified histology confirmed the presence of a pseudarthrosis or the presence of a solid fusion, and the results were highly correlated with the manual testing. Although all products claim to have significant osteoinductive capabilities, this study demonstrates that there are significant differences between some of the tested products.
doi:10.1007/s00586-006-0282-x
PMCID: PMC2200779  PMID: 17205237
Demineralized bone matrix; Spine fusion; Osteoinductivity

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