Osteoinductive capacity and heat stability of recombinant human bone morphogenetic protein-2 produced by Escherichia coli and dimerized by biochemical processing

Yano, Koichi; Hoshino, Masanori; Ohta, Yoshiji; Naka, Yoshifumi; Imai, Yuuki; Takaoka, Kunio

doi:10.1016/j.bone.2009.01.036

Cited by 14 publications

(28 citation statements)

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“…The prepared implants were stored at -30°C until implantation. We tested the heat tolerance of E-BMP-2 in a previous study and confirmed that this sterilization process does not affect the activity of rhBMP-2 [43].…”

Section: Preparation Of Bone Graft Substitute Implantssupporting

confidence: 67%

“…The ectopic induction of new bone formation by dimeric E-BMP-2 has already been reported elsewhere [22,32]. Recent studies in our laboratory found that characteristics of E-BMP-2 are satisfactory for clinical use to promote bone healing in place of the currently available BMP-2 produced by BMP-2-expressing CHO cells [12,43]. We therefore consider that achievement of solid interspinous process fusion using this new biodegradable bone-inducing material could address biomechanical weakness in spinal disorders as a less-invasive option without bone grafting.…”

Section: Discussionmentioning

confidence: 55%

“…The Escherichia coli-derived rhBMP-2 (E-BMP-2) used in this study was produced and kindly donated by Osteopharma (Osaka, Japan) [43]. E-BMP-2 with a dimeric molecular structure was produced in human BMP-2 gene-transfected E. coli with a monomeric structure and stored in inclusion bodies, which were collected.…”

Section: Rhbmp-2mentioning

confidence: 99%

“…Dimeric E-BMP-2 was purified using several steps of chromatography. Details of the procedures for dimerization of cytokines have already been reported [12,32,42,43].…”

Section: Rhbmp-2mentioning

confidence: 99%

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Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

et al. 2011

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Introduction As a powerful bone-inducing cytokine, rhBMP-2 has been used as a bone graft substitute in combination with animal-derived collagen to achieve interbody or posterolateral spinal fusion. Successful interspinous process fusion using rhBMP-2 in combination with synthetic carrier materials would offer a safe, minimally invasive spinal fusion option for the treatment of spinal disorders. The aims of the present study were to achieve interspinous process fusion by implanting rhBMP-2-retaining degradable material instead of bone grafting and to evaluate efficacy for vertebral stabilization. Materials and methods A polymer gel (200 mg), btricalcium phosphate powder (400 mg), and rhBMP-2 (0, 30, 60 or 120 lg) were mixed to generate a plastic implant, which was then placed during surgery to bridge the L5-6 interspinous processes of 58 rabbits. Control animals received implants either without rhBMP-2 or with autogenous bone chips from the iliac crest. L5-6 vertebrae were recovered 8 weeks postoperatively. Interspinous process fusion was evaluated by radiography, biomechanical bending test, intradiscal pressure (IDP) measurement, and histology. Results In bending tests, strength of fusion was significantly greater in BMP60 and BMP120 groups than in sham, BMP0, BMP30 or autogenous bone groups. IDP at L5-6 was significantly reduced in BMP60 and BMP120 groups compared to sham, BMP0, BMP30, and autograft groups. Histologically, coronal sections of the fusion mass showed a bone mass bridging both spinous processes. ConclusionSolid interspinous process fusion was achieved in rabbit models by 8 weeks after implanting the biodegradable bone-inducing material. These results suggest a potential new less-invasive option without bone grafting for the treatment of lumbar disorders.

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Section: Preparation Of Bone Graft Substitute Implantssupporting

confidence: 67%

Section: Discussionmentioning

confidence: 55%

Section: Rhbmp-2mentioning

confidence: 99%

“…Dimeric E-BMP-2 was purified using several steps of chromatography. Details of the procedures for dimerization of cytokines have already been reported [12,32,42,43].…”

Section: Rhbmp-2mentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

et al. 2011

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“…A previous report has already demonstrated the similar effectiveness of E. coli -derived rhBMP-2 (E-BMP-2) compared to C-BMP-2 in inducing the gene expression of osteogenic marker genes Runx2 and Ocn in a mouse bone marrowderived ST2 cell line [Yano et al, 2009]. Moreover, E-BMP-2 has also been shown to induce ectopic new bone formation in vivo [Yano et al, 2009]. However, the main difference between E-BMP-2 and C-BMP-2 is that E-BMP-2 does not undergo glycosylation, a critical step in protein folding.…”

Section: Introductionmentioning

confidence: 99%

Regeneration of Calvarial Defects with <b><i>Escherichia coli</i></b>-Derived rhBMP-2 Adsorbed in PLGA Membrane

Ono

Sonoyama

Nema

et al. 2013

Cells Tissues Organs

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Objective:Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2. However, several in vitro and in vivo experiments are still necessary to validate the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly related to protein nonglycosylation. The objective of this study was to investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized defects in rat calvaria. Materials and Methods: First, the osteoinductive effect of E-BMP-2 was confirmed in vitro in mouse bone marrow stromal cells by analysis of osteocalcin mRNA levels, and calcium deposition was detected by alizarin red staining. Before in vivo experiments, the release profile of E-BMP-2 from PLGA membranes was determined by ELISA. E-BMP-2 (0, 1, 5 and 10 μg/μl) was applied for ectopic and orthotopic bone formation and was analyzed by X-ray, micro-CT and histology. Results: Release-profile testing showed that PLGA membrane could retain 94% of the initially applied E-BMP-2. Ectopic bone formation assay revealed that combination of E-BMP-2/PLGA membrane strongly induced bone formation. Stronger osteoinductivity with complete repair of critical-sized defects was observed only with PLGA membranes adsorbed with 5 and 10 μg/μl of E-BMP-2, whereas no bone formation was observed in the groups that received no membrane or 0-μg/μl dose of E-BMP-2. Conclusion: PLGA membrane was shown to be a suitable carrier for sustained release of E-BMP-2, and the E-BMP-2/PLGA membrane combination was demonstrated to be efficient in bone regeneration in a model of critical-sized defects.

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Impregnation of β‐tricalcium phosphate robocast scaffolds by in situ polymerization

Martínez‐Vázquez

Perera

Meulen

et al. 2013

J Biomedical Materials Res

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Ring-opening polymerization of ε-caprolactone (ε-CL) and L-lactide (LLA) was performed to impregnate β-tricalcium phosphate (β-TCP) scaffolds fabricated by robocasting. Concentrated colloidal inks prepared from β-TCP commercial powders were used to fabricate porous structures consisting of a 3D mesh of interpenetrating rods. ε-CL and LLA were in situ polymerized within the ceramic structure by using a lipase and stannous octanoate, respectively, as catalysts. The results show that both the macropores inside the ceramic mesh and the micropores within the ceramic rods are full of polymer in either case. The mechanical properties of scaffolds impregnated by in situ polymerization (ISP) are significantly increased over those of the bare structures, exhibiting similar values than those obtained by other, more aggressive, impregnation methods such as melt-immersion (MI). ISP using enzymatic catalysts requires a reduced processing temperature which could facilitate the incorporation of growth factors and other drugs into the polymer composition, thus enhancing the bioactivity of the composite scaffold. The implications of these results for the optimization of the mechanical and biological performance of scaffolds for bone tissue engineering applications are discussed.

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Osteoinductive capacity and heat stability of recombinant human bone morphogenetic protein-2 produced by Escherichia coli and dimerized by biochemical processing

Cited by 14 publications

References 0 publications

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Regeneration of Calvarial Defects with <b><i>Escherichia coli</i></b>-Derived rhBMP-2 Adsorbed in PLGA Membrane

Impregnation of β‐tricalcium phosphate robocast scaffolds by in situ polymerization

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