Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration

Hollinger, Jeffrey O.; Schmitt, John; Buck, David C.; Shannon, Robert; Joh, Seong Pil; Zegzula, H. Daniel; Wozney, John M.

doi:10.1002/(sici)1097-4636(199824)43:4<356::aid-jbm3>3.0.co;2-7

Cited by 188 publications

(115 citation statements)

References 35 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: 94%

“…We have shown previously that reindeer BMP extract is an effective inducer of new bone formation in a muscle pouch model in mice (Pekkarinen et al 2003(Pekkarinen et al , 2004(Pekkarinen et al , 2005b. In the present study, we compared the bone healing properties of the reindeer BMP extract to results with untreated and collagen controls, while rhBMP-2 (InductOS) was also included in the comparisons because the bone healing capacity of rhBMP-2 has been well documented in experimental animal and clinical studies (Hollinger et al 1998, Sciadini and Johnson 2000, Yudell and Block 2000, Govender et al 2002, Li et al 2002.…”

Section: Discussionmentioning

confidence: 99%

“…46.7 µL of the solvent, thus containing 70 µg of rhBMP-2, was pipetted onto the collagen matrix (10 × 20 mm) to form the implant. The dose of rhBMP-2 was determined from the literature (Hollinger et al 1998, Bessho et al 1999, Li et al 2002.…”

Section: Reconstitution Of Implants and Sterilizationmentioning

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: 94%

Section: Discussionmentioning

confidence: 99%

Section: Reconstitution Of Implants and Sterilizationmentioning

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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“…Bone healing was mostly completed after 8 weeks of implantation, although a very low dose of BMP-2 (5 ìg) was loaded onto a graft. This dose was in a similar range to those being used in other matrix based carriers [19,20]. Therefore, the results confirmed the efficacy of the developed delivery system in restoring infected bones.…”

Section: Discussionmentioning

confidence: 99%

Potential of bone scaffolds containing vancomycin and bone morphogenetic protein-2 in a rat model of osteomyelitis

Thanyaphoo

Kaewsrichan

2014

Asian Biomedicine

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Background: Infected bone is often intractable. An ideal approach is to simultaneously eradicate infection and repair the bone defect. The development of osteoinductive bone graft composites to control antibiotic drug release would be useful for the treatment of intractable bone infections. Objectives: To develop a rat model of osteomyelitis for assessing osteoinductive bone graft scaffolds containing antibiotics and a bone morphogenetic protein.Methods: Si-imprinted calcium phosphate is a new hydroxyapatite derivative used in fabricating bone scaffolds. Vancomycin and bone morphogenetic protein-2 (BMP-2) were loaded onto scaffolds of Si-imprinted calcium phosphate using an established method. The efficiency of the scaffold as a drug carrier system was assessed in vivo. Osteomyelitis was induced in rats by infection of the tibial epiphysis with Staphylococcus aureus (BAA 1680). The success of inducing disease was checked after 4 weeks using bacterial culture and radiography. A 10 mm metaphysis bone was surgically removed and replaced with a drug-loaded scaffold. Histology and X-ray imaging were used to evaluate the implants at 8 weeks post implantation. Results: We successfully established a rat model of osteomyelitis. The causative bacteria were effectively eradicated by vancomycin released from the implants. Enhanced bone formation was observed for the implant samples containing vancomycin and BMP-2 compared with those containing either vancomycin or BMP2 alone. Conclusions:The newly developed bone scaffold has potential as a vehicle for therapeutic agents to treat bone diseases.

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Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

Winn

Schmitt

Buck

et al. 1999

J. Biomed. Mater. Res.

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A tissue-engineered bone biomimetic device was developed to regenerate calvaria critical-sized defects (CSDs) in athymic rats. Well-documented evidence clearly confirms that left untreated, CSDs will not spontaneously regenerate bone. To accomplish regeneration, four candidate treatments were assessed: porous poly(D,L-lactide) and type I collagen (PLC), PLC and human osteoblast precursor cells (OPCs) at 2 x 10(5) (PLC/OPCs), PLC and 50 microg of recombinant human bone morphogenetic protein-2 (PLC/rhBMP-2), and PLC/OPCs/rhBMP-2 (the bone biomimetic device). The hypotheses for this study were PLC/OPCs/rhBMP-2 would promote more new bone formation in CSDs than the other treatments and the amount of bone formation would be time dependent. To test the hypotheses, outcomes from treatments were measured at 2 and 4 weeks postoperatively by radiomorphometry for percent radiopacity and by histomorphometry for square millimeters of new bone formation. Data were analyzed by analysis of variance and Fisher's protected least significant difference for multiple comparisons with p< or = 0.05. At 2 and 4 weeks, radiomorphometric data revealed PLC/rhBMP-2 and PLC/OPCs/rhBMP-2 promoted significantly more radiopacity than either PLC or PLC/OPCs. Histomorphometry data at 2 and 4 weeks indicated significantly more new bone formation for PLC/rhBMP-2, PLC/OPCs/rhBMP-2, and PLC/OPCs compared to PLC. By 4 weeks, PLC/OPCs/rhBMP-2 and PLC/rhBMP-2 had regenerated the CSDs with more new bone than the other treatments; the quantity of bone at 4 weeks for these treatments was greater than at 2 weeks.

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Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration

Cited by 188 publications

References 35 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

Potential of bone scaffolds containing vancomycin and bone morphogenetic protein-2 in a rat model of osteomyelitis

Tissue-engineered bone biomimetic to regenerate calvarial critical-sized defects in athymic rats

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