Regeneration of Calvarial Defects with &lt;b&gt;&lt;i&gt;Escherichia coli&lt;/i&gt;&lt;/b&gt;-Derived rhBMP-2 Adsorbed in PLGA Membrane

Ono, M.; Sonoyama, Wataru; Nema, Kazuki; Hara, Emilio Satoshi; Oida, Yasutaka; Pham, Hai Thanh; Yamamoto, Katushi; Hirota, Kazuo; Sugama, Kazushige; Sebald, Walter; Kuboki, Takuo

doi:10.1159/000356947

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…Despite a 110 mg/L production rate of E. coli -derived rhBMP2, its activity and efficacy after refolding is controversial (Bessho et al, 2000 ; Bessa et al, 2008 ; Yano et al, 2009 ; Lee et al, 2010 ). Recently, same preclinical studies showed promising results in using E. coli -produced rhBMP2 for the regeneration of experimentally induced bone defects (Harada et al, 2012 ; Ono et al, 2013 ; Chung et al, 2015 ; You et al, 2016 ), even if the most effective dose as well as the optimal carrier are still to be determined. A comparison between CHO- and E. coli -derived rhBMP2 using a dog critical-size supraalveolar peri-implant model showed that the two rhBMP2s are equally effective in inducing bone formation (Lee et al, 2013 ); however, no economic analysis was provided in this study.…”

Section: Discussionmentioning

confidence: 99%

A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27 kD γ-Zein Accumulates to High Levels in the Endoplasmic Reticulum without Forming Protein Bodies in Transgenic Tobacco

et al. 2016

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Human Bone Morphogenetic Protein-2 (hBMP2) is an osteoinductive agent physiologically involved in bone remodeling processes. A commercialized recombinant hBMP2 produced in mammalian cell lines is available in different clinical applications where bone regeneration is needed, but widespread use has been hindered due to an unfavorable cost/effective ratio. Protein bodies are very large insoluble protein polymers that originate within the endoplasmic reticulum by prolamine accumulation during the cereal seed development. The N-terminal domain of the maize prolamin 27 kD γ-zein is able to promote protein body biogenesis when fused to other proteins. To produce high yield of recombinant hBMP2 active domain (ad) in stably transformed tobacco plants we have fused it to the γ-zein domain. We show that this zein-hBMP2ad fusion is retained in the endoplasmic reticulum without forming insoluble protein bodies. The accumulation levels are above 1% of total soluble leaf proteins, indicating that it could be a rapid and suitable strategy to produce hBMP2ad at affordable costs.

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Section: Discussionmentioning

confidence: 99%

A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27 kD γ-Zein Accumulates to High Levels in the Endoplasmic Reticulum without Forming Protein Bodies in Transgenic Tobacco

et al. 2016

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“…In this context, our research group recently succeeded in producing BMP-2 using an Escherichia coli production system (E-BMP-2), which is particularly attractive for biotechnology because of the ability of E. coli to grow rapidly and at a high density on inexpensive substrates [Kubler et al, 1998;Yano et al, 2009]. Previously, our group demonstrated the osteoinductive capacity of E-BMP-2 in vitro and ectopic and orthotopic bone formation in vivo [Yano et al, 2009;Ono et al, 2013]. In the dental field, several reports have shown that E-BMP-2-coated implants enhance bone-to-implant contact (BIC) [Lee et al, 2013] and bone regeneration in bone closure of a sinus window .…”

Section: Introductionmentioning

confidence: 99%

Efficient Bone Formation in a Swine Socket Lift Model Using <b><i>Escherichia coli-</i></b>Derived Recombinant Human Bone Morphogenetic Protein-2 Adsorbed in β-Tricalcium Phosphate

Ono

Sonoyama

Yamamoto

et al. 2014

Cells Tissues Organs

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Several preclinical studies have shown that Escherichia coli-derived bone morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However, further investigation of the effectiveness and determination of the optimal dosage of E-BMP-2 in large animals are still necessary before its full application in humans. This study investigated the efficiency of different concentrations of E-BMP-2 adsorbed in β-TCP for bone augmentation and osseointegration of immediate dental implants in a swine socket lift model. Following exposure of the maxillary sinus lateral wall, a 3.4-mm (diameter) cavity was drilled and filled with 0.1 g of β-TCP containing different doses of E-BMP-2 (0, 10, 30, or 100 μg/site) to lift the Schneiderian membrane. A dental implant was then immediately inserted. Bone-to-implant contact (BIC) and bone density (BD) examined via histological analysis were used as parameters to assess E-BMP-2 efficiency in bone formation. The implant stability quotient (ISQ) was measured using Osstell to determine the effect of E-BMP-2/β-TCP on implant stability. After 8 weeks, the groups that received 30 and 100 μg of E-BMP-2 showed substantial new bone formation in the elevated space, while no bone formation was observed with β-TCP alone. Accordingly, BIC and BD presented a dose-dependent response to increasing doses of E-BMP-2. However, there was no increase in implant stability with E-BMP-2 treatment. In conclusion, the E-BMP-2/β-TCP combination was efficient in bone formation and osseointegration of dental implants in a socket lift model in mini-pigs.

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“…In the current study, it was shown that in situ gelling hydrogel composite with a concentration of 50 ug/mL BMP-2 (2 µg per implant in a 5 mm defect) successfully regenerated bone. In other preclinical studies with BMP-2 carriers, the BMP-2 dose needed to heal a critical sized defect is generally higher; in a rat calvarial model similar to the one used in the current study, complete healing of the defects is achieved with poly lactic-co-glycolic acid (PLGA) membranes adsorbed with 5 mg/mL of BMP-2 (Ono et al, 2013). Young et al (2009), using a 8 mm rat calvarial model and 0.5 µg and 1 µg of BMP-2 per implant delivered with gelatin particles, show an incomplete bone bridging.…”

Section: Discussionmentioning

confidence: 96%

Injectable BMP-2 delivery system based on collagen-derived microspheres and alginate induced bone formation in a time- and dose-dependent manner

Mumcuoglu

Fahmy-Garcia

Ridwan

et al. 2018

eCM

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The aim of the current study was to reduce the clinically used supra-physiological dose of bone morphogenetic protein-2 (BMP-2) (usually 1.5 mg/mL), which carries the risk of adverse events, by using a more effective release system. A slow release system, based on an injectable hydrogel composed of BMP-2-loaded recombinant collagen-based microspheres and alginate, was previously developed. Time- and dose-dependent subcutaneous ectopic bone formation within this system and bone regeneration capacity in a calvarial defect model were investigated. BMP-2 doses of 10 µg, 3 µg and 1 µg per implant (50 µg/mL, 15 µg/mL and 5 µg/mL, respectively) successfully induced ectopic bone formation subcutaneously in rats in a time- and dose-dependent manner, as shown by micro-computed tomography (µCT) and histology. In addition, the spatio-temporal control of BMP-2 retention was shown for 4 weeks in vivo by imaging of fluorescently-labelled BMP-2. In the subcritical calvarial defect model, µCT revealed a higher bone volume for the 2 µg of BMP-2 per implant condition (50 µg/mL) as compared to the lower dose used (0.2 µg per implant, 5 µg/mL). Complete defect bridging was obtained with 50 µg/mL BMP-2 after 8 weeks. The BMP-2 concentration of 5 µg/mL was not sufficient to heal a calvarial defect faster than the empty defect or biomaterial control without BMP-2. Overall, this injectable BMP-2 delivery system showed promising results with 50 µg/mL BMP-2 in both the ectopic and calvarial rat defect models, underling the potential of this composite hydrogel for bone regeneration therapies.

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

Cited by 12 publications

References 23 publications

A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27 kD γ-Zein Accumulates to High Levels in the Endoplasmic Reticulum without Forming Protein Bodies in Transgenic Tobacco

A Fusion between Domains of the Human Bone Morphogenetic Protein-2 and Maize 27 kD γ-Zein Accumulates to High Levels in the Endoplasmic Reticulum without Forming Protein Bodies in Transgenic Tobacco

Efficient Bone Formation in a Swine Socket Lift Model Using <b><i>Escherichia coli-</i></b>Derived Recombinant Human Bone Morphogenetic Protein-2 Adsorbed in β-Tricalcium Phosphate

Injectable BMP-2 delivery system based on collagen-derived microspheres and alginate induced bone formation in a time- and dose-dependent manner

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