Abstract
Objectives
This study aims to evaluate the expression of various immunohistochemical growth factors and vascularization markers in augmentation on the mandible comparing onlay bone grafts and Guided Bone Regeneration (GBR).
Materials and methods
Using a sheep in vivo model, autogenous bone grafts were harvested from the iliac crest. A combination of a resorbable collagen membrane (CM) and a Deproteinized Bovine Bone Material (DBBM) was performed. This modification of the host side was compared with an onlay bone graft control group. Expression of different vascularization markers was compared between these groups.
Results
The expression of revascularization markers was significantly higher within the modification of the host side using GBR and DBBM. Regarding different graft regions, a significantly higher expression within the bone graft using GBR and DBBM could be observed in staining on bone morphogenetic protein-2 (BMP-2) (5.75 vs. 3.55), vascular endothelial growth factor (VEGF) (3.08 vs. 1.64), VEGF Receptor 1 (VEGFR-1) and VEGF Receptor 2 (VEGFR-2) (4.88 vs. 2.24 and 5.06 vs. 2.74), and endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) (5.29 vs. 3.28 and 5.22 vs. 3.09; p = 0.000, all others p < 0.05), whereas the control group showed a higher rate of resorption during the surveillance period until euthanasia of sheep after 16 weeks.
Conclusion
The use of GBR and DBBM in the transplantation process of autogenous bone grafts compared with the therapeutical use of certain growth factors may enhance vascularization and lower atrophy and resorption.
Clinical relevance
The use of a combination of GBR and DBBM in augmentation procedures on the mandible shows less resorption than simple onlay bone grafts and seems to be superior in a clinical use.
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References
Hjorting-Hansen E (2002) Bone grafting to the jaws with special reference to reconstructive preprosthetic surgery. A historical review Mund Kiefer Gesichtschir 6(1):6–14
Jakse N, Seibert FJ, Lorenzoni M, Eskici A, Pertl C (2001) A modified technique of harvesting tibial cancellous bone and its use for sinus grafting. Clin Oral Implants Res 12(5):488–494
Nkenke E, Schultze-Mosgau S, Radespiel-Troger M, Kloss F, Neukam FW (2001) Morbidity of harvesting of chin grafts: a prospective study. Clin Oral Implants Res 12(5):495–502
Nkenke E, Weisbach V, Winckler E, Kessler P, Schultze-Mosgau S, Wiltfang J, Neukam FW (2004) Morbidity of harvesting of bone grafts from the iliac crest for preprosthetic augmentation procedures: a prospective study. Int J Oral Maxillofac Surg 33(2):157–163. doi:10.1054/ijom.2003.0465
Nkenke E, Radespiel-Troger M, Wiltfang J, Schultze-Mosgau S, Winkler G, Neukam FW (2002) Morbidity of harvesting of retromolar bone grafts: a prospective study. Clin Oral Implants Res 13(5):514–521
Bauer TW, Muschler GF (2000) Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 371:10–27
Khan SN, Cammisa FP Jr, Sandhu HS, Diwan AD, Girardi FP, Lane JM (2005) The biology of bone grafting. J Am Acad Orthop Surg 13(1):77–86
Adeyemo WL, Reuther T, Bloch W, Korkmaz Y, Fischer JH, Zoller JE, Kuebler AC (2008) Influence of host periosteum and recipient bed perforation on the healing of onlay mandibular bone graft: an experimental pilot study in the sheep. Oral Maxillofac Surg 12(1):19–28. doi:10.1007/s10006-008-0098-4
Adeyemo WL, Reuther T, Bloch W, Korkmaz Y, Fischer JH, Zoller JE, Kuebler AC (2008) Healing of onlay mandibular bone grafts covered with collagen membrane or bovine bone substitutes: a microscopical and immunohistochemical study in the sheep. Int J Oral Maxillofac Surg 37(7):651–659. doi:10.1016/j.ijom.2008.02.005
Maiorana C, Beretta M, Salina S, Santoro F (2005) Reduction of autogenous bone graft resorption by means of Bio-Oss coverage: a prospective study. Int J Periodontics Restorative Dent 25(1):19–25
de Carvalho PS, Vasconcellos LW, Pi J (2000) Influence of bed preparation on the incorporation of autogenous bone grafts: a study in dogs. Int J Oral Maxillofac Implants 15(4):565–570
Donos N, Kostopoulos L, Tonetti M, Karring T (2005) Long-term stability of autogenous bone grafts following combined application with guided bone regeneration. Clin Oral Implants Res 16(2):133–139. doi:10.1111/j.1600-0501.2004.01104.x
Lin KY, Bartlett SP, Yaremchuk MJ, Fallon M, Grossman RF, Whitaker LA (1990) The effect of rigid fixation on the survival of onlay bone grafts: an experimental study. Plast Reconstr Surg 86(3):449–456
Jardini MA, De Marco AC, Lima LA (2005) Early healing pattern of autogenous bone grafts with and without e-PTFE membranes: a histomorphometric study in rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100(6):666–673. doi:10.1016/j.tripleo.2005.03.020
Karring T, Nyman S, Gottlow J (2000) Laurell L (1993) Development of the biological concept of guided tissue regeneration—animal and human studies. Periodontol 1:26–35
Dahlin C, Alberius P, Linde A (1991) Osteopromotion for cranioplasty. An experimental study in rats using a membrane technique J Neurosurg 74(3):487–491. doi:10.3171/jns.1991.74.3.0487
Jovanovic SA, Spiekermann H, Richter EJ (1992) Bone regeneration around titanium dental implants in dehisced defect sites: a clinical study. Int J Oral Maxillofac Implants 7(2):233–245
Kostopoulos L, Karring T (1994) Guided bone regeneration in mandibular defects in rats using a bioresorbable polymer. Clin Oral Implants Res 5(2):66–74
Lundgren D, Lundgren AK, Sennerby L, Nyman S (1995) Augmentation of intramembraneous bone beyond the skeletal envelope using an occlusive titanium barrier. An experimental study in the rabbit Clin Oral Implants Res 6(2):67–72
Simion M, Trisi P, Piattelli A (1994) Vertical ridge augmentation using a membrane technique associated with osseointegrated implants. Int J Periodontics Restorative Dent 14(6):496–511
Araujo MG, Sonohara M, Hayacibara R, Cardaropoli G, Lindhe J (2002) Lateral ridge augmentation by the use of grafts comprised of autologous bone or a biomaterial. An experiment in the dog J Clin Periodontol 29(12):1122–1131
Guillemin G, Patat JL, Fournie J, Chetail M (1987) The use of coral as a bone graft substitute. J Biomed Mater Res 21(5):557–567. doi:10.1002/jbm.820210503
Holmes RE (1979) Bone regeneration within a coralline hydroxyapatite implant. Plast Reconstr Surg 63(5):626–633
Galindo-Moreno P, Avila G, Fernandez-Barbero JE, Aguilar M, Sanchez-Fernandez E, Cutando A, Wang HL (2007) Evaluation of sinus floor elevation using a composite bone graft mixture. Clin Oral Implants Res 18(3):376–382. doi:10.1111/j.1600-0501.2007.01337.x
Hallman M, Sennerby L, Lundgren S (2002) A clinical and histologic evaluation of implant integration in the posterior maxilla after sinus floor augmentation with autogenous bone, bovine hydroxyapatite, or a 20:80 mixture. Int J Oral Maxillofac Implants 17(5):635–643
Remmele W, Schicketanz KH (1993) Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract 189(8):862–866
De Marco AC, Jardini MA, Lima LP (2005) Revascularization of autogenous block grafts with or without an e-PTFE membrane. Int J Oral Maxillofac Implants 20(6):867–874
Dongieux JW, Block MS, Morris G, Gardiner D, Dean K (1998) The effect of different membranes on onlay bone graft success in the dog mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86(2):145–151
Donos N, Kostopoulos L, Karring T (2002) Augmentation of the rat jaw with autogeneic cortico-cancellous bone grafts and guided tissue regeneration. Clin Oral Implants Res 13(2):192–202
Donos N, Kostopoulos L, Karring T (2002) Alveolar ridge augmentation by combining autogenous mandibular bone grafts and non-resorbable membranes. Clin Oral Implants Res 13(2):185–191
Donos N, Kostopoulos L, Karring T (2002) Alveolar ridge augmentation using a resorbable copolymer membrane and autogenous bone grafts. An experimental study in the rat Clin Oral Implants Res 13(2):203–213
Fonseca RJ, Clark PJ, Burkes EJ Jr, Baker RD (1980) Revascularization and healing of onlay particulate autologous bone grafts in primates. J Oral Surg 38(8):572–577
Verhoeven JW, Ruijter J, Cune MS, Terlou M, Zoon M (2000) Onlay grafts in combination with endosseous implants in severe mandibular atrophy: one year results of a prospective, quantitative radiological study. Clin Oral Implants Res 11(6):583–594
Enneking WF, Burchardt H, Puhl JJ, Piotrowski G (1975) Physical and biological aspects of repair in dog cortical-bone transplants. J Bone Joint Surg Am 57(2):237–252
Smith JD, Abramson M (1974) Membranous vs. endochondrial bone autografts. Arch Otolaryngol 99(3):203–205
Zins JE, Whitaker LA (1983) Membranous versus endochondral bone: implications for craniofacial reconstruction. Plast Reconstr Surg 72(6):778–785
Iizuka T, Smolka W, Hallermann W, Mericske-Stern R (2004) Extensive augmentation of the alveolar ridge using autogenous calvarial split bone grafts for dental rehabilitation. Clin Oral Implants Res 15(5):607–615. doi:10.1111/j.1600-0501.2004.01043.x
Alberius P, Dahlin C, Linde A (1992) Role of osteopromotion in experimental bone grafting to the skull: a study in adult rats using a membrane technique. J Oral Maxillofac Surg 50(8):829–834
Jensen OT, Greer RO Jr, Johnson L, Kassebaum D (1995) Vertical guided bone-graft augmentation in a new canine mandibular model. Int J Oral Maxillofac Implants 10(3):335–344
Lundgren AK, Lundgren D, Sennerby L, Taylor A, Gottlow J, Nyman S (1997) Augmentation of skull bone using a bioresorbable barrier supported by autologous bone grafts. An intra-individual study in the rabbit Clin Oral Implants Res 8(2):90–95
Donos N, Kostopoulos L, Karring T (2002) Augmentation of the mandible with GTR and onlay cortical bone grafting. An experimental study in the rat Clin Oral Implants Res 13(2):175–184
Hardwick R, Hayes BK, Flynn C (1995) Devices for dentoalveolar regeneration: an up-to-date literature review. J Periodontol 66(6):495–505
von Arx T, Broggini N, Jensen SS, Bornstein MM, Schenk RK, Buser D (2005) Membrane durability and tissue response of different bioresorbable barrier membranes: a histologic study in the rabbit calvarium. Int J Oral Maxillofac Implants 20(6):843–853
Carinci F, Piattelli A, Degidi M, Palmieri A, Perrotti V, Scapoli L, Martinelli M, Laino G, Pezzetti F (2006) Genetic effects of anorganic bovine bone (Bio-Oss) on osteoblast-like MG63 cells. Arch Oral Biol 51(2):154–163. doi:10.1016/j.archoralbio.2005.06.006
Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573):439–442. doi:10.1038/380439a0
Yang R, Thomas GR, Bunting S, Ko A, Ferrara N, Keyt B, Ross J, Jin H (1996) Effects of vascular endothelial growth factor on hemodynamics and cardiac performance. J Cardiovasc Pharmacol 27(6):838–844
Street J, Bao M, deGuzman L, Bunting S, Peale FV Jr, Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RA, Filvaroff EH (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci USA 99(15):9656–9661. doi:10.1073/pnas.152324099
Ohtsubo S, Matsuda M, Takekawa M (2003) Angiogenesis after sintered bone implantation in rat parietal bone. Histol Histopathol 18(1):153–163
Caballero-Alias AM, Loveridge N, Lyon A, Das-Gupta V, Pitsillides A, Reeve J (2004) NOS isoforms in adult human osteocytes: multiple pathways of NO regulation? Calcif Tissue Int 75(1):78–84. doi:10.1007/s00223-003-0161-y
Corbett SA, Hukkanen M, Batten J, McCarthy ID, Polak JM, Hughes SP (1999) Nitric oxide in fracture repair. Differential localisation, expression and activity of nitric oxide synthases. J Bone Joint Surg Br 81(3):531–537
Korkmaz Y, Baumann MA, Schroder H, Behrends S, Addicks K, Raab WH, Bloch W (2004) Localization of the NO-cGMP signaling pathway molecules, NOS III-phosphorylation sites, ERK1/2, and Akt/PKB in osteoclasts. J Periodontol 75(8):1119–1125. doi:10.1902/jop.2004.75.8.1119
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This work was supported by a grant of Deutsche Forschungsgemeinschaft, Germany.
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Koerdt, S., Ristow, O., Wannhoff, A. et al. Expression of growth factors during the healing process of alveolar ridge augmentation procedures using autogenous bone grafts in combination with GTR and an anorganic bovine bone substitute. Clin Oral Invest 18, 179–188 (2014). https://doi.org/10.1007/s00784-013-0938-y
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DOI: https://doi.org/10.1007/s00784-013-0938-y