Journal List > J Korean Acad Prosthodont > v.51(2) > 1034772

Huh, Yun, Jeong, Shin, and Jeon: Combined effects of rhBMP-2 and rhVEGF coated onto implants on osseointegration: pilot study

Abstract

Purpose

The present study is aimed to evaluate the combined effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) coated onto anodized implants on osseointeration.

Materials and methods

Six New Zealand white rabbit were used in this study. Each animal received 4 implants that were either coated with rhBMP-2 and rhVEGF (Study group) or anodized implant (Control group) in both tibia. This was performed using a randomized split-mouth design. A total 24 implants were used. The implant stability quotient (ISQ) value using resonance frequency analyser and removal torque (RTQ) measurement were investigated at 2 and 8 weeks. The t-test was used for statistical analysis (α =.05).

Results

Control and study group showed good osseointegration at 8 weeks. The ISQ and RTQ values of study group were significant compared with the control group at 8 weeks (P<.05). However, No statistical significance was observed at 2 weeks (P>.05).

Conclusion

It was concluded that rhBMP-2 with rhVEGF coated onto anodized implants can induce better osseointegration at late healing period. (J Korean Acad Prosthodont 2013;51:82-9)

REFERENCES

1.Retzepi M., Lewis MP., Donos N. Effect of diabetes and metabolic control on de novo bone formation following guided bone regeneration. Clin Oral Implants Res. 2010. 21:71–9.
crossref
2.Sykaras N., Woody RD., Lacopino AM., Triplett RG., Nunn ME. Osseointegration of dental implants complexed with rhBMP-2: a comparative histomorphometric and radiographic evaluation. Int J Oral Maxillofac Implants. 2004. 19:667–78.
3.Sumner DR., Turner TM., Urban RM., Turek T., Seeherman H., Wozney JM. Locally delivered rhBMP-2 enhances boneingrowth and gap healing in a canine model. J Orthop Res. 2004. 22:58–65.
4.Becker J., Kirsch A., Schwarz F., Chatzinikolaidou M., Rothamel D., Lekovic V., Laub M., Jennissen HP. Bone apposition to titanium implants biocoated with recombinant human bone morphogenetic protein-2 (rhBMP-2). A pilot study in dogs. Clin Oral Investig. 2006. 10:217–24.
crossref
5.Huh JB., Ryu JJ., Kim JE., Kim DW., Kim SJ., Park YB., Kim YS., Lee SY., Lee JY., Shin SW. Effects of anodized implants coated with Escherichia coli-derived recombinant Human bone morphogenetic protein-2 on osseointegration in rabbits. Tissue Eng Regen Med. 2011. 8:62–8.
6.Huh JB., Kim SE., Kim HE., Kang SS., Choi KH., Jeong CM., Lee JY., Shin SW. Effects of anodized implants coated with Escherichia coli-derived rhBMP-2 in beagle dogs. Int J Oral Maxillofac Surg. 2012. 41:1577–84.
crossref
7.Huh JB., Park CK., Kim SE., Shim KM., Choi KH., Kim SJ., Shim JS., Shin SW. Alveolar ridge augmentation using anodized implants coated with Escherichia coli-derived recombinant human bone morphogenetic protein 2. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011. 112:42–9.
crossref
8.Stenport VF., Johansson C., Heo SJ., Aspenberg P., Albrektsson T. Titanium implants and BMP-7 in bone: an experimental model in the rabbit. J Mater Sci Mater Med. 2003. 14:247–54.
9.Schliephake H., Aref A., Scharnweber D., Bierbaum S., Roessler S., Sewing A. Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation. Clin Oral Implants Res. 2005. 16:563–9.
crossref
10.Park J., Lutz R., Felszeghy E., Wiltfang J., Nkenke E., Neukam FW., Schlegel KA. The effect on bone regeneration of a liposomal vector to deliver BMP-2 gene to bone grafts in peri-implant bone de-fects. Biomaterials. 2007. 28:2772–82.
crossref
11.Stadlinger B., Pilling E., Huhle M., Mai R., Bierbaum S., Scharnweber D., Kuhlisch E., Loukota R., Eckelt U. Evaluation of osseointegration of dental implants coated with collagen, chondroitin sulphate and BMP-4: an animal study. Int J Oral Maxillofac Surg. 2008. 37:54–9.
crossref
12.Kim SE., Yun YP., Lee JY., Shim JS., Park K., Huh JB. Co-delivery of platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) coated onto heparinized titanium for improving osteoblast function and osteointegration. J Tissue Eng Regen Med. 2013 Jan 3.
crossref
13.Huh JB., Lee JY., Lee KL., Kim SE., Yun MJ., Shim JS., Shim JS., Shin SW. Effects of the immobilization of heparin and rhPDGF-BB to titanium surfaces for the enhancement of osteoblastic functions and anti-inflammation. J Adv Prosthodont. 2011. 3:152–60.
crossref
14.Ferrara N., Gerber HP., LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003. 9:669–76.
crossref
15.Senger DR., Van de Water L., Brown LF., Nagy JA., Yeo KT., Yeo TK., Berse B., Jackman RW., Dvorak AM., Dvorak HF. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev. 1993. 12:303–24.
crossref
16.Zelzer E., Olsen BR. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol. 2005. 65:169–87.
crossref
17.Harper J., Klagsbrun M. Cartilage to bone-angiogenesis leads the way. Nat Med. 1999. 5:617–8.
crossref
18.Rabie AB., Shum L., Chayanupatkul A. VEGF and bone formation in the glenoid fossa during forward mandibular positioning. Am J Orthod Dentofacial Orthop. 2002. 122:202–9.
crossref
19.Deckers MM., Karperien M., van der Bent C., Yamashita T., Papapoulos SE., Lo¨wik CW. Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology. 2000. 141:1667–74.
crossref
20.Peng H., Wright V., Usas A., Gearhart B., Shen HC., Cummins J., Huard J. Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF and bone morphogenetic protein-4. J Clin Invest. 2002. 110:751–9.
crossref
21.Patel ZS., Young S., Tabata Y., Jansen JA., Wong ME., Mikos AG. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone. 2008. 43:931–40.
crossref
22.Byrne AM., Bouchier-Hayes DJ., Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med. 2005. 9:777–94.
crossref
23.Wang DS., Miura M., Demura H., Sato K. Anabolic effects of 1,25-dihydroxyvitamin D3 on osteoblasts are enhanced by vascular endothelial growth factor produced by osteoblasts and by growth factors produced by endothelial cells. Endocrinology. 1997. 138:2953–62.
crossref
24.Mayr-Wohlfart U., Waltenberger J., Hausser H., Kessler S., Gu¨nther KP., Dehio C., Puhl W., Brenner RE. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone. 2002. 30:472–7.
crossref
25.Hall J., Sorensen RG., Wozney JM., Wikesjo¨ UM. Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model. J Clin Periodontol. 2007. 34:444–51.
crossref
26.Wikesjo¨ UM., Qahash M., Polimeni G., Susin C., Shanaman RH., Rohrer MD., Wozney JM., Hall J. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observations. J Clin Periodontol. 2008. 35:1001–10.
27.Samee M., Kasugai S., Kondo H., Ohya K., Shimokawa H., Kuroda S. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) transfection to human periosteal cells enhances osteoblast differentiation and bone formation. J Pharmacol Sci. 2008. 108:18–31.
crossref
28.Huang YC., Kaigler D., Rice KG., Krebsbach PH., Mooney DJ. Combined angiogenic and osteogenic factor delivery enhances bone marrow stromal cell-driven bone regeneration. J Bone Miner Res. 2005. 20:848–57.
crossref
29.Kanczler JM., Ginty PJ., White L., Clarke NM., Howdle SM., Shakesheff KM., Oreffo RO. The effect of the delivery of vascular endothelial growth factor and bone morphogenic protein-2 to os-teoprogenitor cell populations on bone formation. Biomaterials. 2010. 31:1242–50.
crossref
30.Li G., Corsi-Payne K., Zheng B., Usas A., Peng H., Huard J. The dose of growth factors influences the synergistic effect of vascular endothelial growth factor on bone morphogenetic protein 4-induced ectopic bone formation. Tissue Eng Part A. 2009. 15:2123–33.
crossref
31.Ramazanoglu M., Lutz R., Ergun C., von Wilmowsky C., Nkenke E., Schlegel KA. The effect of combined delivery of recombinant human bone morphogenetic protein-2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium-phosphate-coated implants on osseointegration. Clin Oral Implants Res. 2011. 22:1433–9.
crossref
32.Buser D., Broggini N., Wieland M., Schenk RK., Denzer AJ., Cochran DL., Hoffmann B., Lussi A., Steinemann SG. Enhanced bone apposition to a chemically modified SLA titanium surface. J Dent Res. 2004. 83:529–33.
crossref
33.Le Guehennec L., Goyenvalle E., Lopez-Heredia MA., Weiss P., Amouriq Y., Layrolle P. Histomorphometric analysis of the os-seointegration of four different implant surfaces in the femoral epiphyses of rabbits. Clin Oral Implants Res. 2008. 19:1103–10.
crossref
34.Stadlinger B., Pilling E., Huhle M., Mai R., Bierbaum S., Bernhardt R., Scharnweber D., Kuhlisch E., Hempel U., Eckelt U. Influence of extracellular matrix coatings on implant stability and os-seointegration: an animal study. J Biomed Mater Res B Appl Biomater. 2007. 83:222–31.
crossref
35.Lioubavina-Hack N., Lang NP., Karring T. Significance of primary stability for osseointegration of dental implants. Clin Oral Implants Res. 2006. 17:244–50.
crossref
36.Liu Y., de Groot K., Hunziker EB. BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model. Bone. 2005. 36:745–57.
crossref
37.Luo T., Zhang W., Shi B., Cheng X., Zhang Y. Enhanced bone regeneration around dental implant with bone morphogenetic protein 2 gene and vascular endothelial growth factor protein de- livery. Clin Oral Implants Res. 2012. 23:467–73.
38.Schmid J., Wallkamm B., Ha¨mmerle CH., Gogolewski S., Lang NP. The significance of angiogenesis in guided bone regeneration. A case report of a rabbit experiment. Clin Oral Implants Res. 1997. 8:244–8.
crossref
39.Sojo K., Sawaki Y., Hattori H., Mizutani H., Ueda M. Immunohistochemical study of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2, -4 (BMP-2, -4) on lengthened rat femurs. J Craniomaxillofac Surg. 2005. 33:238–45.
crossref

Fig. 1.
Procedures of surgery in rabbit tibia. A: marking the incision area, B: exposure of tibia, C: marking the insertion portion, D: implant insertion.
jkap-51-82f1.tif
Fig. 2.
The measurements of implant stability and removal torque. A: Osstell Mentor for implant stability quotient value, B: removal torque gauge MGT12 for removal torque measurement.
jkap-51-82f2.tif
Fig. 3.
Mean and standard deviation of ISQ values in each group.
jkap-51-82f3.tif
Fig. 4.
Mean and standard deviation of RTQ values in each group.
jkap-51-82f4.tif
Table 1.
The means and SD of each group in different intervals
Group ISQ value (mean ± SD) RTQ value (mean ± SD)
Post OP 2 weeks 8 weeks 2 weeks 8 weeks
Control 55.67 ± 13.94 60.50 ± 6.83 66.83 ± 3.66 20.99 ± 3.48 30.28 ± 6.50
Study 56.34 ± 16.77 54.33 ± 10.02 77.83 ± 6.18 20.61 ± 3.59 43.42 ± 7.93

RTQ: removal torque measurements, ISQ: implant stability quotient.

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