Release of recombinant human bone morphogenetic protein 2 from a newly developed carrier

Yokota, Shoji; Uchida, Tomoyuki; Kokubo, Satoshi; Aoyama, K; Fukushima, Shinji; Nozaki, Kazutoshi; Takahashi, Tomoya; Fujimoto, Ryuhei; Sonohara, R; Yoshida, Mutsumi; Higuchi, S.; Yokohama, Shigeharu; Sonobe, Takashi

doi:10.1016/s0378-5173(02)00581-1

Cited by 18 publications

(26 citation statements)

References 11 publications

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“…The PGS carrier used in this study possesses some therapeutic advantages as a carrier for rhBMP-2 and FGF-2, since it is 1) easy to apply, 2) able to retain rhBMP-2 and FGF-2 at a bone regeneration site for a period of time sufficient to induce bone formation, 3) able to provide space for bone regeneration due to its stiffness, and 4) noncytotoxic. Furthermore, PGS retained an appropriate amount of rhBMP-2 at the orthotopically implanted site for at least 3 weeks enough to induce bone regeneration, 41 which suggested that PGS has sufficient ability in controlling the release of rhBMP-2. These characteristics are almost consistent with those that a successful rhBMP-2 carrier needs.…”

Section: Discussionmentioning

confidence: 99%

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Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity

et al. 2006

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The osteoinductive activity induced by recombinant human BMP-2 (rhBMP-2) blunts proportionately as the recipient ages. In order to compensate for this bluntness administration of fibroblast growth factor-2 (FGF-2) has been considered. The aim of this study was to determine whether FGF-2 administration augments osteoinductive activity caused by rhBMP-2 and to evaluate the effect of aging on bone formation induced by coadministration of rhBMP-2 and FGF-2. Sixty-four Wistar strain male rats of 8-week-old (prepubertal) and 16-week-old (postpubertal) received bone defects bilaterally in the parietal bone and the defects were filled by a polylactic acid polyglycolic acid copolymer/gelatin sponge (PGS) impregnated with rhBMP-2 plus 0 ng, 25 ng, and 250 ng FGF-2 (n=10 in each). At 2 weeks after grafting, the new bone volume seemed to be larger in the rhBMP-2+FGF-2 groups than in the rhBMP-2 alone group. At 4 weeks, the new bone formation was linked to the adjacent original bone. In the prepubertal rats, all newly formed bone was similarly calcified. In the postpubertal rats, only the rhBMP-2+25 ng FGF-2 group showed this higher degree of calcification. At 2 weeks, alkaline phosphatase (ALP) activity in the rhBMP-2+25 ng FGF-2 group was significantly (p<0.05) larger than that in the rhBMP-2 group in both prepubertal and postpubertal rats. This result shows that low-dose administration of FGF-2 enhanced the degree of calcification and ALP activity in the rhBMP-2 grafting site especially in the postpubertal rats. Therefore, FGF-2 would be a candidate to compensate for the reduction of osteoinductive activity of rhBMP-2 with aging.

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Section: Discussionmentioning

confidence: 99%

“…If the optimal carriers are used, rhBMP-2 and FGF-2 remain in the carrier for 3 weeks and 2 weeks, respectively. 41 The decline of the bone volume increase from 2 to 4 weeks after implantation of the graft may therefore be caused by a long time release of FGF-2.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity

et al. 2006

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“…This apposition of radiopacity might occur due to loadbearing to the induced bone, rather than to the continuous effect of implanted rhBMP-2. These speculations are supported by the reports describing that load-bearing positively affects bone formation as well as bone remodeling [26,27], and that radioactivity of 125 Ilabeled rhBMP-2 in PGS at the implant site was eliminated in a biphasic manner (t1/2a: 0.1 days, t1/2b: 3 days) and declined to 0.5% of the administered amount by 3 weeks post-implantation in a rabbit long bone defect model [28]. One regenerated tibia was fractured due to loosening of cast fixation at 1 week after plate removal (conducted at postoperative week 16).…”

Section: Discussionmentioning

confidence: 56%

Long-term stability of bone tissues induced by an osteoinductive biomaterial, recombinant human bone morphogenetic protein-2 and a biodegradable carrier

Kokubo¹,

Mochizuki

Fukushima³

et al. 2004

Biomaterials

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“…This method would obviate protein extraction and could also be used for the in vitro and in vivo release measurements. [20][21][22][23][24][25][26] The PLGA microspheres were incorporated into the PPF scaffold in an attempt to better maintain local in vivo concentrations at osteoinductive levels for sufficient time. The impregnation of PPF scaffolds with a high BMP-2 dose is inherent to minimal retention and failed to consistently produce bone inside the scaffolds.…”

Section: Discussionmentioning

confidence: 99%

Effect of Autologous Bone Marrow Stromal Cell Seeding and Bone Morphogenetic Protein-2 Delivery on Ectopic Bone Formation in a Microsphere/Poly(Propylene Fumarate) Composite

Kempen

Kruyt

et al. 2009

Tissue Engineering Part A

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A biodegradable microsphere=scaffold composite based on the synthetic polymer poly(propylene fumarate) (PPF) holds promise as a scaffold for cell growth and sustained delivery vehicle for growth factors for bone regeneration. The objective of the current work was to investigate the in vitro release and in vivo bone forming capacity of this microsphere=scaffold composite containing bone morphogenetic protein-2 (BMP-2) in combination with autologous bone marrow stromal cells (BMSCs) in a goat ectopic implantation model. Three composites consisting of 0, 0.08, or 8 mg BMP-2 per mg of poly(lactic-co-glycolic acid) microspheres, embedded in a porous PPF scaffold, were combined with either plasma (no cells) or culture-expanded BMSCs. PPF scaffolds impregnated with a BMP-2 solution and combined with BMSCs as well as empty PPF scaffolds were also tested. The eight different composites were implanted subcutaneously in the dorsal thoracolumbar area of goats. Incorporation of BMP-2-loaded microspheres in the PPF scaffold resulted in a more sustained in vitro release with a lower burst phase, as compared to BMP-2-impregnated scaffolds. Histological analysis after 9 weeks of implantation showed bone formation in the pores of 11=16 composites containing 8 mg=mg BMP-2-loaded microspheres with no significant difference between composites with or without BMSCs (6=8 and 5=8, respectively). Bone formation was also observed in 1=8 of the BMP-2-impregnated scaffolds. No bone formation was observed in the other conditions. Overall, this study shows the feasibility of bone induction by BMP-2 release from microspheres=scaffold composites.

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Release of recombinant human bone morphogenetic protein 2 from a newly developed carrier

Cited by 18 publications

References 11 publications

Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity

Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity

Long-term stability of bone tissues induced by an osteoinductive biomaterial, recombinant human bone morphogenetic protein-2 and a biodegradable carrier

Effect of Autologous Bone Marrow Stromal Cell Seeding and Bone Morphogenetic Protein-2 Delivery on Ectopic Bone Formation in a Microsphere/Poly(Propylene Fumarate) Composite

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