Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects

Shinohara, Yukiya; Nakamura, Toshiaki; Shirakata, Yoshinori; Noguchi, Kazuyuki

doi:10.4012/dmj.2015-242

Cited by 17 publications

(22 citation statements)

References 32 publications

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“…ACS has been shown to maintain its structure within calvarial bone defects, without collapsing, possibly because of a slow biodegradation of the cross‐linked collagen . Moreover, ACS can help to prevent diffusion of embedded cells when transplanted into bone defects .…”

Section: Discussionsupporting

confidence: 85%

“…An absorbable ACS (5 mm in diameter and 3 mm thick, MIGHTY; KOKEN, Tokyo, Japan) was used as a scaffold. Atelocollagen, which originates from type I collagen extracted from bovine dermis, was freeze‐dried, then cross‐linked and sterilized to produce the ACS . The ACS contains interconnected 30–200 μm pores …”

Section: Methodsmentioning

confidence: 99%

“…ACS possesses mechanical structural features and properties that facilitate the ready supply of nutrients to cells, and its use could prevent cell diffusion . An ACS was shown to be a suitable carrier for growth factors, such as bone morphogenetic protein‐9, to induce bone formation in a rat calvarial defect model . Moreover, ACSs have been used as a scaffold for transplantation of osteoblast‐like cells and umbilical cord perivascular cells for bone regeneration.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro

Hisanaga

Suzuki

Aoki

et al. 2017

J of Periodontal Research

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro

Hisanaga

Suzuki

Aoki

et al. 2017

J of Periodontal Research

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“…Moreover, it was observed by Sreekumar et al that rhBMP9 treatment in human osteoblasts from 110 donors showed several advantages including higher alkaline phosphatase (ALP) activity and Smad nuclear translocation when compared to rhBMP2 and rhBMP7 by following distinct and unique signaling cascades . Thus far, two rodent studies have also demonstrated the effectiveness of rhBMP9 treatment on new bone formation when compared to untreated control sites in rat calvarial defects . However, bone inductive potential of rhBMP9 had not been investigated when compared to rhBMP2 in the animal muscle.…”

Section: Introductionmentioning

confidence: 99%

Superior bone‐inducing potential of rhBMP9 compared to rhBMP2

Fujioka‐Kobayashi

Raouf

Saulačić

et al. 2018

J Biomedical Materials Res

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Recombinant human bone morphogenic protein (rhBMP) 9 has recently been reported to have more osteopromotive potential in vitro when compared to rhBMP2. The aim of the present study was to investigate the bone-inducing potential of rhBMP2 and rhBMP9. We compared rhBMP2, rhBMP7, and rhBMP9 at five different concentrations and showed convincingly that rhBMP9 possesses much greater potential for osteoblast differentiation even at 20 times lower concentrations in vitro. We further show that Noggin, an inhibitor for rhBMP2-induced osteogenesis, did not alter rhBMP9-induced osteogenesis. Thereafter, we show for the first time that rhBMP9 loaded onto atelo-collagen membranes is osteoinductive and has greater potential to form ectopic bone formation when compared to rhBMP2 even at four times lower doses. Similarly new bone formation of rhBMP2 and 9 when loaded on deproteinized bovine bone mineral (DBBM) was investigated in a rabbit calvarial defect. At 8 weeks, both rhBMP2 and rhBMP9 induced significantly higher new bone formation when compared to DBBM alone samples. Interestingly, once again four times lower dose of rhBMP9 group induced comparable or even greater levels of new bone height and new bone area when compared to the rhBMP2 group. The present study revealed that (1) rhBMP9 is capable of inducing ectopic new bone formation in vivo and (2) up to four times lower doses of rhBMP9 may be utilized to regenerate same-size bone defects when compared to rhBMP2. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1561-1574, 2018.

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“…Further research utilizing rhBMP9 would benefit our understanding on the differential mechanisms that regulate osteogenesis in both BMP2 versus BMP9. One group currently reported that rhBMP9 loaded on atelocollagen and chitosan sponges promoted new bone formation in rat critical‐sized bone defect (Toshiaki Nakamura et al, 2016; Shinohara, Nakamura, Shirakata, & Noguchi, 2016). The further animal studies in comparison with rhBMP2 are now necessary to further verify bone regenerative potential of rhBMP9.…”

Section: Discussionmentioning

confidence: 99%

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

Fujioka‐Kobayashi

Benoit

Saulačić

et al. 2017

Clinical & Exp Dental Res

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The use of growth factors for the regeneration of soft and hard tissues has been utilized extensively in dental medicine over the past decade. Recently our group found that recombinant human bone morphogenetic protein 9 (rhBMP9) was more osteopromotive than recombinant human bone morphogenetic protein 2 (rhBMP2) when combined with a deprotenized bovine bone mineral bone grafting material. The aim of the present in vitro study was to evaluate the regenerative potential of an absorbable collagen sponge(ACS) specifically designed for extraction socket healing loaded with rhBMP9 when compared to rhBMP2. The adsorption and release kinetics of rhBMP2 and rhBMP9 were first investigated by enzyme‐linked immunosorbent assay quantification. Then, the cellular effects of stromal cell line (ST2) preosteoblasts were investigated utilizing four groups including rhBMP2 and rhBMP9 at both low(10 ng/ml) and high(100 ng/ml) concentrations loaded onto ACS. Cellular attachment(8 hours) and proliferation(1, 3, and 5 days) as well as osteoblast differentiation were investigated by real‐time polymerase chain reaction (PCR) at 3 and 14 days, alkaline phosphatase (ALP) activity at 7 days, and alizarin red staining at 14 days. ACS fully adsorbed both rhBMP2 and rhBMP9 that were slowly released up to 10 days. Although neither rhBMP2 nor rhBMP9 had any effects on cell attachment or proliferation, pronounced effects were observed on osteoblast differentiation. ALP activity was increased seven‐fold with rhBMP2‐high, whereas a marked 10‐fold and 20‐fold increase was observed with rhBMP9‐low and high loaded to ACS, respectively. Furthermore, mRNA levels of collagen1, ALP, bone sialoprotein, and osteocalcin were all significantly higher for rhBMP9 when compared to control or rhBMP2 groups. Alizarin red staining further confirmed that rhBMP9‐low and high demonstrated marked increases in mineralization potential when compared to rhBMP2‐high. The results demonstrate the marked effect of rhBMP9 on osteoblast differentiation when combined with ACS in comparison to rhBMP2 at doses as much as 10 times lower. Further in vivo studies are necessary to investigate whether the regenerative potential is equally as potent.

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Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects

Cited by 17 publications

References 32 publications

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro

Superior bone‐inducing potential of rhBMP9 compared to rhBMP2

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

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