Bone regeneration by recombinant human bone morphogenetic protein-2 and a novel biodegradable carrier in a rabbit ulnar defect model

Kokubo, Satoshi; Fujimoto, Ryuhei; Yokota, Shoji; Fukushima, Shinji; Nozaki, Kazutoshi; Takahashi, Koichiro; Miyata, Keiji

doi:10.1016/s0142-9612(02)00551-3

Cited by 84 publications

(58 citation statements)

References 28 publications

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“…BMPs combined with different carrier materials have been shown to heal experimental bone defects in many studies (Moore et al 1990, Viljanen et al 1996, Hollinger et al 1998, Sciadini and Johnson 2000, Tuominen et al 2000, Yudell and Block 2000, Chen et al 2002, Kokubo et al 2003, Barboza et al 2004. Until now, there have been no studies investigating the ability of reindeer BMP extract to heal long bone defects.…”

Section: Discussionmentioning

confidence: 99%

“…Many previous studies concerning the ability of BMPs to promote healing of long bone defects have been performed using synthetic polymer carriers or composite implants containing collagen and frames such as coral, tricalcium phosphate or hydroxyapatite , Tuominen et al 2000, Hu et al 2003, Kokubo et al 2003. In the present study we did not use composite implants because the rabbit radius is a relatively small bone and its critical-size bone defect does not require extra fixation or a carrier that is mechanically stronger than collagen.…”

Section: Discussionmentioning

confidence: 99%

“…The bone-healing properties of different recombinant and extracted BMPs have been studied using long bone defect models in rabbits (Hollinger et al 1998, Kokubo et al 2003, dogs Johnson 2000, Tuominen et al 2000), rats (Takagi and Urist 1982, Chen et al 2002, Matsuo et al 2003 and sheep (Gao et al , 1997. Favorable results in preclinical and clinical trials have also led to the regulatory approval of different commercial recombinant BMP products for some clinical purposes by government agencies (Burkus et al 2002a,b, Govender et al 2002, ValentinOpran et al 2002, Matsuo et al 2003.…”

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confidence: 99%

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Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

Pekkarinen¹,

Jämsä

Määttä

et al. 2006

Acta Orthopaedica

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Background Native BMP extracts from reindeer effectively induce ectopic new bone formation in vivo, but their bone healing properties have not yet been evaluated. We investigated the effect of reindeer BMP extracts on the healing of long bone defects.Methods The implants tested contained 5 mg or 10 mg of unsterilized BMP extract from reindeer and 10 mg of gamma-sterilized BMP extract administered with collagen carrier (Lyostypt, B. Braun, Germany). 70 µg of rhBMP-2 with collagen carrier (InductOs; Wyeth Europa) served as positive control, and collagen implants (Lyostypt) and untreated defects served as negative controls. New Zealand White rabbits with 1.5 cm of critical-size radius bone defects were used, with 8 weeks of follow-up.Results Radiographic analysis showed bone formation (BF) to be higher in all groups containing BMPs than in the untreated controls. BF was also higher in the rhBMP-2 group, and marginally higher in the group treated with 10 mg of unsterilized reindeer BMP extract (p = 0.06) as compared to the collagen controls. Bone union (BU) was better in the unsterilized BMP extract groups and rhBMP-2 group than in the untreated controls. BU was also better in the implants with 10 mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated implants. The mean area of new bone at the site of the defect proved to be higher in all implants containing BMP than in the untreated defects. It was also higher in the groups with 10 mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated controls. Mechanical tests showed torsional stiffness of the bones to be higher in the group with 10 mg of unsterilized BMP extract than in the collagen

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

Pekkarinen¹,

Jämsä

Määttä

et al. 2006

Acta Orthopaedica

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“…This type of imaging helps in the assessment of the efficacies of different therapeutic approaches in bone pathologies involving a significant loss of substance or in subjects with production deficit of the bone callus. In particular, there is high interest in the development of novel biomimetic materials with osteogenic properties, which can also be associated with cellular therapies (Granero-Molto et al, 2008;Kokubo et al, 2003).…”

Section: Bone Imagingmentioning

confidence: 99%

High-Resolution CT for Small-Animal Imaging Research

Badea

Panetta²

2014

Comprehensive Biomedical Physics

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“…15 Among the many factors, bone morphogenetic protein (BMP)-2 and BMP-7 in particular have been shown to have a significant effect on bone regeneration. [16][17][18][19][20][21] Other growth factors out of the transforming growth factor b (TGFb) superfamily are expected to have similar effects. In different models, TGFb-1 and TGFb-2 have been reported to have an osteoinductive potential.…”

Section: Introductionmentioning

confidence: 99%

Mechanical and radiological assessment of the influence of rhTGFβ‐3 on bone regeneration in a segmental defect in the ovine tibia: Pilot study

Maissen

Eckhardt

Gogolewski

et al. 2006

Journal Orthopaedic Research

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Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFb-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFb-3 seeded on a poly(L/DL-lactide) carrier (n ¼ 4). In a second group (n ¼ 4), the defect was treated by the carrier only, in a third group (n ¼ 4) by autologous cancellous bone graft, and in a fourth group (n ¼ 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFb-3 group ( p ¼ 0.06) and a significantly higher increase than in the PLA-only group ( p ¼ 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups ( p ¼ 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm 3 ) performing better than the PLA/rhTGFb-3 (38%; 0.23 g/cm 3 ) and the PLA-only treatment (2.5%; 0.09 g/cm 3 ), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFb-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation. ß

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Bone regeneration by recombinant human bone morphogenetic protein-2 and a novel biodegradable carrier in a rabbit ulnar defect model

Cited by 84 publications

References 28 publications

Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit

High-Resolution CT for Small-Animal Imaging Research

Mechanical and radiological assessment of the influence of rhTGFβ‐3 on bone regeneration in a segmental defect in the ovine tibia: Pilot study

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