Hydroxyapatite Granule Graft Combined With Recombinant Human Bone Morphogenic Protein-2 for Solid Lumbar Fusion

Konishi, Sadahiko; Nakamura, Hiroaki; Seki, Mitsunori; Nagayama, Ryuichi; Yamano, Yoshiki

doi:10.1097/00024720-200206000-00013

Cited by 28 publications

(26 citation statements)

References 29 publications

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“…This was accomplished by the use of either animal-derived collagen sheets, hydroxyapatite with collagen, an open cell polylactic acid polymer, or sintered bovine bone as the delivery system for rhBMP-2. 5,10,[12][13][14][15] Interestingly, in this study, the minimal effective dose of rhBMP-2 was significantly lower (15-30 g) than the amounts used in previous studies. Those prior experiments were not reproduced in this study; therefore, a direct comparison of the minimal effective dose of rhBMP is difficult.…”

Section: Discussioncontrasting

confidence: 67%

“…[5][6][7][8][9][10][11][12][13][14][15] To elicit the BMPinduced bone formation, a carrier material that delivers BMP slowly to the target cells is essential. As a carrier material, animal-derived collagen has been used routinely both in animal experiments and in clinical settings despite the potential risks for immunologic reaction in the host and transfer of diseases such as bovine spongiform encephalopathy (BSE).…”

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confidence: 99%

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Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Delivered by a Synthetic Polymer and β-Tricalcium Phosphate in a Rabbit Model

Namikawa¹,

Terai²,

Suzuki³

et al. 2005

Spine

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Section: Discussioncontrasting

confidence: 67%

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confidence: 99%

Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Delivered by a Synthetic Polymer and β-Tricalcium Phosphate in a Rabbit Model

Namikawa¹,

Terai²,

Suzuki³

et al. 2005

Spine

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“…3,4,[11][12][13] Namikawa et al used b-tricalcium phosphate and PLA-DX-PEG polymer gel as a carrier and successfully reduced rhBMP-2 doses to 15-30 mg to achieve solid spine fusion in the rabbit model. 14 In this study, the results showed 2.5 mg of rhBMP-2 alone using alginate sheet could not induce intertransverse bone formation.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells

Chen

et al. 2009

Journal Orthopaedic Research

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We tested the hypothesis that the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) required to induce spine fusion can be reduced by combination with mesenchymal stem cells (MSCs). Twenty-four adult rabbits underwent posterolateral intertransverse fusion at the L4-L5 level. The animals were divided into four groups based on the implant material: autologous iliac graft, Alginate-MSCs composite, Alginate-BMP-2-MSCs composite, and Alginate-BMP-2 composite. After 16 weeks, the rabbits were euthanized for radiographic examination, manual palpation, biomechanical testing, and histology. Radiographic union of 12 intertransverse fusion areas for the autogenous iliac graft, Alginate-MSCs, Alginate-BMP-2-MSCs, and Alginate-BMP-2 groups was 11, 8, 11, and 0, respectively. Moreover, manual palpation of six fusion segments in each subgroup found solid union to be 6, 1, 5, and 0, respectively. The average torques at failure of the first three groups were 2278 AE 135, 1943 AE 140, and 2334 AE 187 N-mm, respectively. The failure torque did not differ significantly between the autograft and Alginate-BMP-2-MSCs groups; both groups were significantly higher than the Alginate-MSCs group. The results indicate that MSCs delivered with in vitro cellular doses of rhBMP-2 are more osteoinductive than MSCs without rhBMP-2. In combination with MSCs, a low dose (2.5 mg) of rh-BMP-2 could enhance bone formation and posterolateral spine fusion success in the rabbit model. 1-4 However, limitations exist in related clinical applications, including the inconsistent fusion rate and the high cost associated with the high dosage required for osteoinductive factors.During the recent decade, numerous investigators have described techniques for isolating human and animal mesenchymal stem cells (MSCs) from bone marrow.5-7 Culturing MSCs with dexamethasone, ascorbic acid, and b-glycerophosphate directs the cells into the osteogenic lineage.6,7 Additionally, recombinant human bone morphogenetic proteins (rhBMP) were reported to enhance the osteogenic potency of MSCs. 8,9 Theoretically, low-dose rhBMP-2 can improve the osteogenic potency of preconditioned MSCs and can then be used to improve the success of spinal fusion.We tested the hypothesis that rhBMP-2 can enhance the osteogenic potency of preconditioned MSCs and that the dosage of rhBMP-2 to induce intertransverse spine fusion could be lower than previously required.

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“…We have used hydroxyapatite ceramic as a bone scaffold for extensive bone replacement. Hydroxyapatite is composed of calcium phosphate and is incorporated into bone as a physiological minera 2,11,12,15,23,31) . It is not antigenic, carcinogenic, or osteogenic.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Spinal Fusion Using Bone Marrow Derived Mesenchymal Stem Cells with or without Fibroblast Growth Factor-4

Seo

Jung

Lim

et al. 2009

J Korean Neurosurg Soc

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Objective : In this study, the authors assessed the ability of rat bone marrow derived mesenchymal stem cells (BMDMSCs), in the presence of a growth factor, fibroblast growth factor-4 (FGF-4) and hydroxyapatite, to act as a scaffold for posterolateral spinal fusion in a rat model. Methods : Using a rat posterolateral spine fusion model, the experimental study comprised 3 groups. Group 1 was composed of 6 animals that were implanted with 0.08 gram hydroxyapatite only. Group 2 was composed of 6 animals that were implanted with 0.08 gram hydroxyapatite containing 1 × 10 6 / 60 µL rat of BMDMSCs. Group 3 was composed of 6 animals that were implanted with 0.08 gram hydroxyapatite containing 1 × 10 6 / 60 µL of rat BMDMSCs and FGF-4 1 µG to induce the bony differentiation of the BMDMSCs. Rats were assessed using radiographs obtained at 4, 6, and 8 weeks postoperatively. After sacrifice, spines were explanted and assessed by manual palpation, high-resolution microcomputerized tomography, and histological analysis. Results : Radiographic, high-resolution microcomputerized tomographic, and manual palpation revealed spinal fusion in five rats (83%) in Group 2 at 8 weeks. However, in Group 1, three (60%) rats developed fusion at L4-L5 by radiography and two (40%) by manual palpation in radiographic examination. In addition, in Group 3, bone fusion was observed in only 50% of rats by manual palpation and radiographic examination at this time.Conclusion : The present study demonstrates that 0.08 gram of hydroxyapatite with 1 × 10 6 / 60 µL rat of BMDMSCs induced bone fusion. FGF-4, added to differentiate primitive 1 × 10 6 / 60 µL rat of BMDMSCs did not induce fusion. Based on histologic data, FGF-4 appears to induce fibrotic change rather than differentiation to bone by 1 × 10 6 / 60 µL rat of BMDMSCs.

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Hydroxyapatite Granule Graft Combined With Recombinant Human Bone Morphogenic Protein-2 for Solid Lumbar Fusion

Cited by 28 publications

References 29 publications

Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Delivered by a Synthetic Polymer and β-Tricalcium Phosphate in a Rabbit Model

Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Delivered by a Synthetic Polymer and β-Tricalcium Phosphate in a Rabbit Model

Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells

Evaluation of Spinal Fusion Using Bone Marrow Derived Mesenchymal Stem Cells with or without Fibroblast Growth Factor-4

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