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http://dx.doi.org/10.4047/jkap.2013.51.2.82

Combined effects of rhBMP-2 and rhVEGF coated onto implants on osseointegration: pilot study  

Huh, Jung-Bo (Department of Prosthodontics, School of Dentistry, Pusan National University)
Yun, Mi-Jung (Department of Prosthodontics, School of Dentistry, Pusan National University)
Jeong, Chang-Mo (Department of Prosthodontics, School of Dentistry, Pusan National University)
Shin, Sang-Wan (Department of Prosthodontics, Institute for Clinical Dental Research, Korea University Guro Hospital)
Jeon, Young-Chan (Department of Prosthodontics, School of Dentistry, Pusan National University)
Publication Information
The Journal of Korean Academy of Prosthodontics / v.51, no.2, 2013 , pp. 82-89 More about this Journal
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 (${\alpha}$=.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.
Keywords
rhBMP-2; rhVEGF; Implant stability quotient; Removal torque; Osseointegration;
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1 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 osteoprogenitor cell populations on bone formation. Biomaterials 2010;31:1242-1250.   DOI   ScienceOn
2 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;15:2123-2133   DOI   ScienceOn
3 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;22:1433-1439.   DOI   ScienceOn
4 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;83:529-533.   DOI   ScienceOn
5 Le Guehennec L, Goyenvalle E, Lopez-Heredia MA, Weiss P, Amouriq Y, Layrolle P. Histomorphometric analysis of the osseointegration of four different implant surfaces in the femoral epiphyses of rabbits. Clin Oral Implants Res 2008;19:1103-1110   DOI   ScienceOn
6 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 osseointegration: an animal study. J Biomed Mater Res B Appl Biomater 2007;83:222-231.
7 Lioubavina-Hack N, Lang NP, Karring T. Significance of primary stability for osseointegration of dental implants. Clin Oral Implants Res 2006;17:244-250.   DOI   ScienceOn
8 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;36:745-757.   DOI   ScienceOn
9 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 delivery. Clin Oral Implants Res 2012;23:467-473.   DOI   ScienceOn
10 Schmid J, Wallkamm B, Hammerle 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;8:244-248.   DOI   ScienceOn
11 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: 238-245.   DOI   ScienceOn
12 Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-676.   DOI   ScienceOn
13 Rabie AB, Shum L, Chayanupatkul A. VEGF and bone formation in the glenoid fossa during forward mandibular positioning. Am J Orthod Dentofacial Orthop 2002;122:202-209.   DOI   ScienceOn
14 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;12:303-324.   DOI   ScienceOn
15 Zelzer E, Olsen BR. Multiple roles of vascular endothelial growth factor (VEGF) in skeletal development, growth, and repair. Curr Top Dev Biol 2005;65:169-187.
16 Harper J, Klagsbrun M. Cartilage to bone-angiogenesis leads the way. Nat Med 1999;5:617-618.   DOI   ScienceOn
17 Deckers MM, Karperien M, van der Bent C, Yamashita T, Papapoulos SE, Lowik CW. Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology 2000;141:1667-1674.   DOI
18 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;110:751-759.   DOI   ScienceOn
19 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;43:931-940.   DOI   ScienceOn
20 Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med 2005;9:777-794.   DOI   ScienceOn
21 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;138:2953-2962.   DOI
22 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.   DOI   ScienceOn
23 Mayr-Wohlfart U, Waltenberger J, Hausser H, Kessler S, Gunther KP, Dehio C, Puhl W, Brenner RE. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone 2002;30:472-477.   DOI   ScienceOn
24 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;34:444-451.   DOI   ScienceOn
25 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;35:1001-1010.   DOI   ScienceOn
26 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;20:848-857.
27 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;21:71-79.   DOI   ScienceOn
28 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;19:667-678.
29 Sumner DR, Turner TM, Urban RM, Turek T, Seeherman H, Wozney JM. Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model. J Orthop Res 2004;22:58-65.   DOI   ScienceOn
30 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;217-224.   DOI
31 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;8:62-68.
32 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;41:1577-1584.   DOI   ScienceOn
33 Huh JB, Park CK, Kim SE, Shim KM, Choi KH, Kim SJ, Shim JS, Shin SW. Alveolar ridge augmentation using an-odized implants coated with Escherichia coli-derived recombinant human bone morphogenetic protein 2. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:42-49.   DOI   ScienceOn
34 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;14:247-254.
35 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;16:563-569.   DOI   ScienceOn
36 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 defects. Biomaterials 2007;28:2772-2782.   DOI   ScienceOn
37 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;37:54-59   DOI   ScienceOn
38 Huh JB, Lee JY, Lee KL, Kim SE, Yun MJ, Shim JS, Shim JS, Shin SW. Effects of the immobilization of heparin and rhPDGFBB to titanium surfaces for the enhancement of osteoblastic functions and anti-inflammation. J Adv Prosthodont 2011;3:152-160.   DOI   ScienceOn
39 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.