Short-term Osteoclastic Activity Induced by Locally High Concentrations of Recombinant Human Bone Morphogenetic Protein–2 in a Cancellous Bone Environment

Toth, Jeffrey M.; Boden, Scott D.; Burkus, J. Kenneth; Badura, Jeffrey M.; Peckham, Steven M.; McKay, William F.

doi:10.1097/brs.0b013e3181952695

Cited by 92 publications

(89 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations are consistent with in vitro and preclinical studies reporting that BMP-2 upregulates osteoclast differentiation and activity [58][59][60][61] and drives osteoclastmediated resorption at high doses. 62 Similar observations have been made for rhBMP-2 released from an ACS implanted in femoral condyle plug defects in sheep. 62 However, transient allograft resorption observed in previous studies has generally been associated with doses of rhBMP-2 considerably higher than the recommended values.…”

supporting

confidence: 66%

“…62 Similar observations have been made for rhBMP-2 released from an ACS implanted in femoral condyle plug defects in sheep. 62 However, transient allograft resorption observed in previous studies has generally been associated with doses of rhBMP-2 considerably higher than the recommended values. Exogenous rhBMP-2 also modified the degradation kinetics of the poly(ester urethane) network.…”

supporting

confidence: 66%

See 1 more Smart Citation

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

Dumas

Prieto

Zienkiewicz

et al. 2014

Tissue Engineering Part A

View full text Add to dashboard Cite

There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling.

show abstract

supporting

confidence: 66%

supporting

confidence: 66%

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

Dumas

Prieto

Zienkiewicz

et al. 2014

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…BMP2 and BMP7 homodimers were reported to accelerate bone formation efficiently. However, the use of the BMP homodimers is associated with a high cost 5,24) and potential side-effects 25) . BMP 2/7 heterodimers have been proposed to overcome the disadvantages of BMP homodimers.…”

Section: Discussionmentioning

confidence: 99%

BMP2/7 heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer

Sun

Wang

Zheng

et al. 2012

Dental Materials Journal

View full text Add to dashboard Cite

This study aimed to compare the effects of bone morphogenetic protein BMP2/7 heterodimer and BMP homodimers on bone regeneration in bone defects model. Identical peri-implant bone defects model were created using proper controls on the frontal skull in 18 minipigs. Collagen sponges with low-dose (30 ng/mL) BMP2/7 heterodimer, BMP2 or BMP7 homodimer were filled in the defects. New bone formation and the expression of type I collagen (Col1), alkaline phosphatase (ALP) and osteocalcin (OCN) were evaluated after 2, 3, and 6 weeks of implantation. BMP2/7 resulted in significantly higher new bone areas percentage in the defect region than BMP2 and BMP7 (p<0.05). Immunohistochemical staining of Col1, ALP and OCN was stronger in BMP2/7 group than BMP2, BMP7 and control group (p<0.05). These results demonstrate that BMP2/7 heterodimer is a stronger inducer of osteoblastogenesis and could be applied at low dose to reduce the cost and side effects of BMP homodimers.

show abstract

“…The existence of a larger depot of entrapped and incidentally adsorbed proteins in association with the porous structure than with the fibrous structures would account for the phenomenon (Wu et al in press). Burst release of BMP-2 may cause a transient local high concentration of BMPs that may potentially over-stimulate the osteoclastic activity (Toth et al 2009) and compromise early osteogenic activities (Zheng et al 2010), etc. Therefore, further efforts should be made to reduce the 'burst release'.…”

mentioning

confidence: 99%

Biomimetic coatings for bone tissue engineering of critical-sized defects

Liu

Groot

2010

J. R. Soc. Interface.

123

119

View full text Add to dashboard Cite

The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a low concentration to be effective. This then mimics the natural method of cytokine release. For this purpose, a suitable vehicle was developed, the so-called biomimetic coating, which can be deposited on metal implants as well as on biomaterials. Materials that are currently used to fill bony defects cannot by themselves trigger bone formation. Therefore, biological functionalization of such materials by the biomimetic method resulted in a novel biomimetic coating onto different biomaterials. Bone morphogenetic protein 2 (BMP-2)-incorporated biomimetic coating can be a solution for a large bone defect repair in the fields of dental implantology, maxillofacial surgery and orthopaedics. Here, we review the performance of the biomimetic coating both in vitro and in vivo.

show abstract

Short-term Osteoclastic Activity Induced by Locally High Concentrations of Recombinant Human Bone Morphogenetic Protein–2 in a Cancellous Bone Environment

Cited by 92 publications

References 51 publications

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

BMP2/7 heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer

Biomimetic coatings for bone tissue engineering of critical-sized defects

Contact Info

Product

Resources

About