Bone formation at recombinant human bone morphogenetic protein‐2‐coated titanium implants in the posterior mandible (Type II bone) in dogs

Wikesjö, Ulf M.E.; Xiropaidis, Andreas V.; Qahash, Mohammed; Lim, Won Hee; Sorensen, Rachel G.; Rohrer, Michael D.; Wozney, John M.; Hall, Jan

doi:10.1111/j.1600-051x.2008.01318.x

Cited by 60 publications

(87 citation statements)

References 13 publications

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“…In our model, suboptimal BMP-2 doses were defined as lower than the ED 50 of 1.2 mg, while the optimal dose was determined as no higher than 5.0 mg due to a plateau effect using higher doses. Previous studies from our research group using canine 43,44 and non-human primate 45 models demonstrated that comparatively higher BMP-2 doses are associated with delayed bone maturation in craniofacial settings. This finding appears explained by an increased local inflammatory response to higher doses of BMP-2, also evidenced by frequent seroma formation 46 and increased remodeling/resorption rates of the adjoining resident bone.…”

Section: Discussionmentioning

confidence: 83%

“…This finding appears explained by an increased local inflammatory response to higher doses of BMP-2, also evidenced by frequent seroma formation 46 and increased remodeling/resorption rates of the adjoining resident bone. [43][44][45] Importantly, over longer healing intervals, bone maturation obscures these effects. It is noteworthy to point out that, based on the manufacturer's recommendations, our study only used *0.5%-10% BMP-2 per implant compared with that of the commercial product.…”

Section: Discussionmentioning

confidence: 99%

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Low-Dose Bone Morphogenetic Protein-2/Stromal Cell-Derived Factor-1β Cotherapy Induces Bone Regeneration in Critical-Size Rat Calvarial Defects

Herberg

Susin

Peláez

et al. 2014

Tissue Engineering Part A

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Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1b, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1b enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1b to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1b potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1b potentiates suboptimal BMP-2 (0.5 mg) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0 mg) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1b provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Low-Dose Bone Morphogenetic Protein-2/Stromal Cell-Derived Factor-1β Cotherapy Induces Bone Regeneration in Critical-Size Rat Calvarial Defects

Herberg

Susin

Peláez

et al. 2014

Tissue Engineering Part A

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“…Wikesjo et al 10,19,37 X (***) X (*) 29. Wikesjo et al 10,19,37 X (***) X (*****) 30. Wikesjo et al 10,19,37 X (***) X (*)…”

Section: Study Characteristics and Descriptive Resultsunclassified

“…Schliephake et al 36 RGD Collagen 1 Dog Mandible 12. Schliephake et al 26 HA 10,19,37 BMP-2 Dog Mandible Table III shows 19 studies with its surface components, animal models, and implant location.…”

Section: Synthesis Of Meta-analysis Resultsmentioning

confidence: 99%

“…Also, it is possible that GF activity is reduced due to the immobilization process. 9,10,15,16,19,[23][24][25]28,[35][36][37] The same considerations apply to the other growth factors used (Table III), perhaps even to a greater degree as their effects on bone growth can be expected to be generally lower than that of BMP. 38 There was only one exception to the negligible effect of GF on BIC that can be seen if only pig models are considered (see later).…”

Section: Effect Of Coatingmentioning

confidence: 98%

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A systematic review and meta‐analysis on the influence of biological implant surface coatings on periimplant bone formation

Jenny

Jauernik

Bierbaum

et al. 2016

J Biomedical Materials Res

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This systematic review and meta-analysis evaluated the influence of biological implant surface coatings on periimplant bone formation in comparison to an uncoated titanium reference surface in experimental large animal models. The analysis was structured according to the PRISMA criteriae. Of the1077 studies, 30 studies met the inclusion criteriae. Nineteen studies examined the bone implant contact (BIC) and were included in the meta-analysis. Overall, the mean increase in BIC for the test surfaces compared to the reference surfaces was 3.7 percentage points (pp) (95% CI -3.9-11.2, p = 0.339). Analyzing the increase in BIC for specific coated surfaces in comparison to uncoated reference surfaces, inorganic surface coatings showed a significant mean increase in BIC of 14.7 pp (95% CI 10.6-18.9, p < 0.01), extracellular matrix (ECM) surface coatings showed an increase of 10.0 pp (95% CI 4.4-15.6, p < 0.001), and peptide coatings showed a statistical trend with 7.1 pp BIC increase (95% CI -0.8-15.0, p = 0.08). In this review, no statistically significant difference could be found for growth factor surface coatings (observed difference -3.3 pp, 95% CI -16.5-9.9, p = 0.6). All analyses are exploratory in nature. The results show a statistically significant effect of inorganic and ECM coatings on periimplant bone formation. Abstract: This systematic review and meta-analysis evaluated the influence of biological implant surface coatings on periimplant bone formation in comparison to an uncoated titanium reference surface in experimental large animal models. The analysis was structured according to the PRISMA criteriae. Of the1077 studies, 30 studies met the inclusion criteriae. Nineteen studies examined the bone implant contact (BIC) and were included in the meta-analysis. Overall, the mean increase in BIC for the test surfaces compared to the reference surfaces was 3.7 percentage points (pp) (95% CI 23.9-11.2, p 5 0.339). Analyzing the increase in BIC for specific coated surfaces in comparison to uncoated reference surfaces, inorganic surface coatings showed a significant mean increase in BIC of 14.7 pp (95% CI 10.6-18.9, p < 0.01), extracellular matrix (ECM) surface coatings showed an increase of 10.0 pp (95% CI 4.4-15.6, p < 0.001), and peptide coatings showed a statistical trend with 7.1 pp BIC increase (95% CI 20.8-15.0, p 5 0.08). In this review, no statistically significant difference could be found for growth factor surface coatings (observed difference 23.3 pp, 95% CI 216.5-9.9, p 5 0.6). All analyses are exploratory in nature. The results show a statistically significant effect of inorganic and ECM coatings on periimplant bone formation.

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Engineering of Dental Tissues: Scaffolds and Preclinical Models

Plachokova

Yang

et al. 2013

Stem Cells in Craniofacial Development and Regeneration

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Bone formation at recombinant human bone morphogenetic protein‐2‐coated titanium implants in the posterior mandible (Type II bone) in dogs

Abstract: rhBMP-2 adsorbed onto TPO implant surfaces initiates dose-dependent peri-implant bone re-modelling resulting in the formation of normal, physiologic bone and clinically relevant osseointegration within 8 weeks.

Cited by 60 publications

References 13 publications

Low-Dose Bone Morphogenetic Protein-2/Stromal Cell-Derived Factor-1β Cotherapy Induces Bone Regeneration in Critical-Size Rat Calvarial Defects

Low-Dose Bone Morphogenetic Protein-2/Stromal Cell-Derived Factor-1β Cotherapy Induces Bone Regeneration in Critical-Size Rat Calvarial Defects

A systematic review and meta‐analysis on the influence of biological implant surface coatings on periimplant bone formation

Engineering of Dental Tissues: Scaffolds and Preclinical Models

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