BMP-2-Mediated Regeneration of Large-Scale Cranial Defects in the Canine: An Examination of Different Carriers
ABSTRACT Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge is a U.S. Food and Drug Administration-approved therapy shown to be an effective means of generating bone formation in multiple clinical settings. However, the optimum dose and delivery of rhBMP-2 to the calvaria are undetermined. The aim of the authors' study was to investigate the use of rhBMP-2 in addressing calvarial defects in a large-animal model through a variety of modifications to this U.S. Food and Drug Administration-approved therapy.
Twenty-three adult canines underwent the creation of a standard calvarial defect and received either no treatment, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with corticocancellous chips, 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules, or 0.4 mg/ml rhBMP-2 in a compression-resistant matrix carrier. Direct comparisons of defect radiopacity were performed at 0, 8, 16, and 24 weeks postoperatively before the animals were euthanized. All specimens were evaluated qualitatively with histology.
Surgical control animals had an average defect radiopacity of 32.7 percent at study completion compared with an average of 99.95 percent across all treatment groups. Ectopic bone formation was found consistently in all treatment groups with varying degrees of severity. Regenerated bone thickness, compactness, and organization varied qualitatively between groups.
Treatment with 0.2 mg/ml rhBMP-2 in an absorbable collagen sponge with MasterGraft Granules showed the least amount of ectopic bone formation and the most compact bone formation within the defect, and produced reasonably consistent bony thickness across the defect. Future studies should focus on spatial regulation of rhBMP-2 to minimize unwanted bone formation.
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ABSTRACT: To determine the possibility of synergistically enhancing orthodontic tooth movement (OTM) and bone formation in vivo by administering bone morphogenetic protein type 2 (BMP-2) on the tension side or in combination with corticotomy on the pressure side. The sample consisted of 56 Wistar rats that were subjected to experimental OTM for 32 days using a split-mouth design. The sample was divided into 4 groups: a control group, a corticotomy group, a BMP-2 group, and a corticotomy plus BMP-2 group. An OTM force of 10 cN was applied to each group. BMP-2 18 μL was administered locally on the tension side alone or in conjunction with corticotomy and then compared with the controls using fluorescence-based tartrate-resistant acid phosphatase staining for osteoclast counts, histologic bone resorption, and clinical OTM results. Corticotomy surgery increased the OTM rate (P < .05) by more than 20%. The injection of BMP-2 alone on the tension side did not induce significant changes in the degree of OTM compared with the vehicle-treated or control group (P > .05). When BMP-2 was combined with corticotomy on the tension and pressure sides (corticotomy plus BMP-2 group), respectively, nonsignificant OTM rates were observed (P > .05) compared with the controls; however, decreased osteoclast counts, bone resorption, and clinical results were observed in the corticotomy plus BMP-2 group. In contrast to reports published to date, the present preliminary study suggests that there are limits to OTM acceleration by bone formation on the tension side and agrees with the idea that there is a single continuous periodontal compartment in OTM, rather than a pressure side and a tension side.Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 02/2012; 70(2):e124-32. DOI:10.1016/j.joms.2011.10.020 · 1.28 Impact Factor
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ABSTRACT: Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases.Advanced drug delivery reviews 03/2012; 64(12):1239-56. DOI:10.1016/j.addr.2012.03.004 · 12.71 Impact Factor
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ABSTRACT: Background : Particulate bone graft and recombinant human bone morphogenetic protein-2 (rhBMP-2) are options for inlay cranioplasty in children who have not developed a diploic space. The purpose of this study was to determine whether particulate bone graft or rhBMP-2 has superior efficacy for inlay cranioplasty and to compare these substances to split cranial bone. Methods : A 17 mm × 17 mm critical-sized defect was made in the parietal bones of 22 rabbits and managed in four ways: Group I (no implant; n=5), Group II (particulate bone graft; n=5), Group III (rhBMP-2; n=7), and Group IV (split cranial bone graft; n=5). Animals underwent microcomputed tomography and histologic analysis 16 weeks after cranioplasty. Results : Defects without an implant (Group I) demonstrated inferior ossification (41.4%; interquartile range [IQR], 28.9% to 42.5%) compared to those treated with particulate bone graft (Group II: 99.5%; IQR, 97.8% to 100%), rhBMP-2 (Group III: 99.6%; IQR, 99.5% to 100%), or split cranial bone (Group IV: 100%) (p < .0001). There was no difference between Groups II, III, and IV (p = .1). Defects treated with rhBMP-2 exhibited thinner bone (0.90 mm; IQR, 0.64 to 0.98) than particulate bone graft (1.95 mm; IQR, 1.09 to 2.83) or split cranial bone (1.72 mm; IQR, 1.54 to 1.88) (p = .006); particulate and split cranial bone grafted defects had a similar thicknesses (p= .6). Conclusions : Particulate bone graft, rhBMP-2, and split cranial bone close inlay calvarial defects equally, although the thickness of bone healed with rhBMP-2 is inferior. Clinically, particulate bone graft or split cranial bone graft may be superior to rhBMP-2 for inlay cranioplasty.The Cleft Palate-Craniofacial Journal 05/2012; 50(3). DOI:10.1597/11-273 · 1.11 Impact Factor