Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph® and PepGen P-15®

DOI: 10.4236/jbnb.2013.41009   PDF   HTML   XML   3,440 Downloads   5,346 Views  


The aim of the present study was to investigate an inorganic bovine-derived hydroxyapatite bone substitute (Osteograph?) mixed with the same biomaterial coated with a synthetic peptide (P-15) analogue of collagen (PepGen P-15?). This blend of bone replacement materials was used for sinus floor augmentation. Assessments were carried out by using histology methods, transmission electron microscopy (TEM) and microanalysis (EDX). Ultrastructural and analytical features of the interfaces between the graft material and the peri-biomaterial tissues were evaluated six months after implantation. Our findings clearly show that newly-formed crystallites first develop at the surface of implanted crystals. Histological investigations revealed new bone tissue linking biomaterial particles together. TEM assessments pointed out that lamellar bone was generally separated from the graft material by a layer of woven bone measuring between 1 and 1.5 μm in thickness. Although calcified bone tissue was observed in direct contact with bone filling particles, the presence of mineralized granular material around implanted particles was also noticed. No characteristic periodic striation of mineralized collagen was evident within that mineralized structure. Chemical analyses (TEM-EDX) realized at different locations of newly formed mineralized granular substance along the interface revealed average Ca/P ratios ranging between 1.02 and 1.63. The different, concomitantly occurring, aforementioned structural features of the interfaces strongly suggested that the host responses to the used biomaterial blend resulted from dynamic osseointegration phenomena related to various interfacial mechanisms. Nevertheless, the biological response to the bone graft material appeared clinically and histologically satisfactory.

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J. Dahlet, A. Boukari, M. Collavini and J. Hemmerlé, "Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph® and PepGen P-15®," Journal of Biomaterials and Nanobiotechnology, Vol. 4 No. 1, 2013, pp. 64-73. doi: 10.4236/jbnb.2013.41009.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] O. H. Tatum, “Maxillary and Sinus Implant Reconstruction,” Dental Clinics of North America, Vol. 30, No. 2, 1986, pp. 207-229.
[2] O. H. Tatum, M. S. Lebowitz, C. A. Tatum and R. A. Borgner, “Sinus Augmentation. Rationale, Development, Long-Term Results,” New York State Dent Journal, Vol. 59, No. 5, 1993, pp. 43-48.
[3] E. Nkenke, V. Weisbach, E. Winckler, P. Kessler, S. Schultze-Mosgau, J. Wiltfang and F. W. Neukam, “Morbidity of Harvesting of Bone Grafts from the Iliac Crest for Preprosthetic Augmentation Procedures: A Prospective Study,” International Journal of Oral and Maxillofacial Surgery, Vol. 33, No. 2, 2004, pp. 157-163. doi:10.1054/ijom.2003.0465
[4] H. Kleinman, R. J. Klebe and G. R. Martin, “Role of Collagenous Matrices in Adhesion and Growth of Cells,” Journal of Cell Biology, Vol. 88, No. 3, 1981, pp. 473-485. doi:10.1083/jcb.88.3.473
[5] L. Masi, A. Franchi, M. Santucci, D. Danielli, L. Arganini, V. Giannone, L. Formigli, S. Benvenuti, A. Tanini, F. Beghi, M. Mian and M. L. Brandi, “Adhesion, Growth, and Matrix Production by Osteoblasts on Collagen Substrata,” Calcified Tissue International, Vol. 51, No. 3, 1992, pp. 202-212. doi:10.1007/BF00334548
[6] R. S. Bhatnagar, J. J. Qian and C. A. Gough, “The Role in Cell Binding of a Beta-Bend within the Triple Helical Region in Collagen Alpha1 (I) Chain: Structural and Biological Evidence for Conformational Tautomerism on Fiber Surface,” Journal of Biomolecular Structure and Dynamics, Vol. 14, No. 5, 1997, pp. 547-560. doi:10.1080/07391102.1997.10508155
[7] J. J. Qian and R. S. Bhatnagar, “Enhanced Cell Attachment to Anorganic Bone Mineral in the Presence of a Synthetic Peptide Related to Col-lagen,” Journal of Biomedical Materials Research, Vol. 31, No. 4, 1996, pp. 545-554. doi:10.1002/(SICI)1097-4636(199608)31:4<545::AID-JBM15>3.0.CO;2-F
[8] R. S. Bhatnagar, J. J. Qian, A. Wedrychowska, M. Sadeghi, Y. M. Wu and N. Smith, “Design of Biomimetic Habitat for Tissue Engineering with P-15, a Synthetic Peptide Analogue of Collagen,” Tissue Engineering, Vol. 5, No. 1, 1999, pp. 53-65. doi:10.1089/ten.1999.5.53
[9] R. S. Bhatnagar, J. J. Qian, A. Wedrychowska, E. Dixon and N. Smith, “Biomimetic Habitat for Cells: Ordered Matrix Deposition and Differentiation in Gingival Fibroblasts Cultured on Hydroxyapatite Coated with a Collagen Analogue,” Cell Mater, Vol. 9, No. 2, 1999, pp. 93-104.
[10] T. E. Lallier, R. Yukna, S. St Marie and R. Moses, “The Putative Collagen Binding Peptide Hastens Periodontal Ligament Cell Attachment to Bone Replacement Graft Materials,” Journal of Periodontology, Vol. 72, No. 8, 2001, pp. 990-997. doi:10.1902/jop.2001.72.8.990
[11] H. Nguyen, J. J. Qian, R. S. Bhatnagar and S. Li, “Enhanced Cell Attachment and Osteoblastic Activity by P-15 Peptide Coated Matrix in Hydrogels,” Biochemical and Biophysical Research Communications, Vol. 311, No. 1, 2003, pp. 179-186. doi:10.1016/j.bbrc.2003.09.192
[12] H. Windhagen and F. Thorey, “Die Funktionelle Reaktion des Knochens auf Mechanische Reize,” Zahnärtzlische Implantolologie, Vol. 16, No. 3, 2000, pp. 139-145.
[13] A. H. Valentin, “Bone Regene-ration through Biomimicry: The New PepGen P-15,” Zahn-heilkunde, Vol. 18, No. 11, 2002, pp. 795-799.
[14] R. A. Yukna, J. T. Krauser, D. P. Callan, G. H. Evans, R. Cruz and M. Martin, “Multi-Center Clinical Comparison of Combination Anorganic Bovine-Derived Hydroxyapatite Matrix (ABM)/Cell Binding Peptide (P-15) and ABM in Human Periodontal Osseous Defects 6-Month Results,” Journal of Periodontology, Vol. 71, No. 11, 2000, pp. 1671-1679. doi:10.1902/jop.2000.71.11.1671
[15] R. A. Yukna, J. T. Krauser, D. P. Callan, G. H. Evans, R. Cruz and M. Martin, “Thirty-Six Months Follow-Ups of 25 Patients Treated with Combination Anorganic Bovine-Derived Hydroxyapatite Matrix (ABM)/Cell-Binding Peptide (P-15) Bone Replacement Grafts in Human Infrabony Defects. I. Clinical Findings,” Journal of Periodontology, Vol. 73, No. 1, 2002, pp. 123-128. doi:10.1902/jop.2002.73.1.123
[16] R. A. Yukna, T. J. Salinas and R. F. Carr, “Periodontal Regeneration Following Use of ABM/P-15: A Case Report,” International Journal of Periodontics and Restorative Dentistry, Vol. 22, 2002, pp. 146-155.
[17] S. Radhakrishnan and C. N. Anusuya, “Comparative Clinical Evaluation of Combination Anorganic Bovine-Derived Hydroxyapatitematrix (ABM)/Cell Binding Peptide (P-15) and Open Flap Debridement (DEBR) in Human Periodontal Osseous Defects: A 6-Month Pilot Study,” Journal of the International Academy of Periodontology, Vol. 6, No. 3, 2004, pp. 101-107.
[18] J. Hahn, M. D. Rohrer and A. J. Tofe, “Clinical, Radio- graphic, Histologic and Histomorphometric Comparison of PepGen P-15® Particulate and PepGen P-15 Flow® in Extraction Sockets. A Same-Mouth Case Study,” Implant Dentistry, Vol. 12, No. 2, 2003, pp. 170-174. doi:10.1097/01.ID.0000064812.39660.FF
[19] D. M. Thompson, M. D. Rohrer and H. S. Prasad, “Comparison of Bone Grafting Materials in Human Extraction Sockets: Clinical, Histologic and Histomorphometric Evaluations,” Implant Dentistry, Vol. 15, No. 1, 2006, pp. 89-96. doi:10.1097/01.id.0000202426.62007.60
[20] R. A. Yukna, J. T. Krauser, D. P. Callan, G. H. Evans, R. Cruz and M. Martin, “Multi-Center Clinical Evaluation of Combination Anorganic Bovine-Derived Hydroxyapatite Matrix (ABM)/Cell Binding Peptide (P-15) as a Bone Replacement Graft Material in Human Periodontal Osseous Defects. 6-Month Results,” Journal of Periodontology, Vol. 69, No. 6, 1998, pp. 655-663. doi:10.1902/jop.1998.69.6.655
[21] E. P. Barboza, R. O. de Souza, A. L. Cauia, L. G. Neto, F. O. Cauia and M. E. Duarte, “Bone Regeneration of Localized Chronic Alveolar Defects Utilizing Cell Binding Peptide Associated with Anorganic Bovine-Derived Bone Mineral: A Clinical and Histological Study,” Journal of Periodontology, Vol. 73, No. 10, 2002, pp. 1153-1159. doi:10.1902/jop.2002.73.10.1153
[22] B. D. S. Tehemar, P. Hanes and M. Sharawy, “Enhancement of Osseointegration of Implant Placed into Extraction Sockets of Healthy and Periodontally Diseased Teeth by Using Graft Material and a PTFE Membrane, or Combination,” Clinical Implant Dentistry and Related Research, Vol. 5, No. 3, 2003, pp. 193-211. doi:10.1111/j.1708-8208.2003.tb00202.x
[23] S. Vastardis, R. A. Yukna, E. T. Mayer and B. L. Atkinson, “Periodontal Regeneration with Peptide-Enhanced Anorganic Bone Matrix in Particulate and Putty form in Dogs,” Journal of Periodontology, Vol. 76, No. 1, 2005, pp. 1690-1696. doi:10.1902/jop.2005.76.10.1690
[24] J. Hahn, “8-Year Onlay Bone Graft and Ridge Augmentation with PepGen P-15®: A Clinical and Radiographic Case Study,” Implant Dentistry, Vol. 13, No. 3, 2004, pp. 228-231. doi:10.1097/01.id.0000136916.28634.d3
[25] D. G. Smiler, “Advances in Endosseous Implant: The Sandwich Split Cortical Graft for Dental Implant Placement,” Dental Implantology Update, Vol. 11, No. 7, 2000, pp. 49-53.
[26] J. T. Krauser, M. D. Rohrer and S. S. Wallace, “Human Histologic and Histomorphometric Analysis Comparing Osteograf®/N with PepGen P-15® in the Maxillary Sinus Elevation Procedure: A Case Report,” Implant Dentistry, Vol. 9, No. 4, 2000, pp. 298-302. doi:10.1097/00008505-200009040-00004
[27] D. G. Smiler, “Comparison of Anorganic Bovine Mineral with and without Synthetic Peptide in a Sinus Elevation: A Case Study,” Implant Dentistry, Vol. 10, No. 2, 2001, pp. 139-142. doi:10.1097/00008505-200104000-00011
[28] M. Degidi, M. Piattelli, A. Scarano, G. Iezzi and A. Piattelli, “Maxillary Sinus Augmentation with a Synthetic Cell-Binding Peptide: Histological and Histomorphometrical Results in Humans,” Journal of Oral Implantology, Vol. 30, No. 6, 2004, pp. 376-383. doi:10.1563/0720.1
[29] A. H. Valentin and J. Weber, “Receptor Technology-Cell Binding to P-15: A New Method of Regenerating Bone Quickly and Safely-Preliminary Histomorphometrical and Mechanical Results in Sinus Floor Augmentations,” Keio Journal of Medicine, Vol. 53, No. 3, 2004, pp. 166-171. doi:10.2302/kjm.53.166
[30] M. Gelbart, R. Friedman, V. Burli, M. Rohmer and B. Atkinson, “Maxillary Sinus Augmentation Using a Peptide-Modified Graft Material in Three Mixtures: A Prospective Human Case Series of Histologic and Histo-morphometric Results,” Implant Dentistry, Vol. 14, No. 2, 2005, pp. 185-193. doi:10.1097/01.id.0000165029.86196.27
[31] P. Philippart, V. Daubie and R. Pochet, “Sinus Grafting Using Recombinant Human Tissue Factor, Platelet-Rich-Plasma Gel, Autologous Bone and Anorganic Bovine Bone Mineral Xenograft: Histologic Analysis and Case Reports,” International Journal of Oral & Maxillofacial Implants, Vol. 20, No. 2, 2005, pp. 274-281.
[32] M. Degidi, A. Scarano, G. Iezzi, G. Orsini, V. Perrotti, R. Strocchi and A. Piattelli, “Maxillary Sinus Augmentation Using a Synthetic Cell-Binding Peptide: A Histologic and Transmission Electon Microscopy Case Study in Man,” Implant Dentistry, Vol. 14, No. 4, 2005, pp. 371-375.
[33] R. W. Yeung, L. J. Jin, M. Pang and E. Pow, “Human Histologic and Electronmicroscopic Analysis with Synthetic Peptide Enhanced Hydroyapatite in the Maxillary Sinus Elevation Procedure: A Case Report,” Implant Dentistry, Vol. 14, No. 3, 2005, pp. 237-241. doi:10.1097/01.id.0000173331.14116.7f
[34] C. Trasatti, R. Spears, J. L. Gutmann and L. A. Opperman, “Increased Tgf-Beta1 Production by Rat Osteoblasts in the Presence of PepGen P-15® in Vitro,” Journal of Endodon, Vol. 30, No. 4, 2004, pp. 213-221. doi:10.1097/00004770-200404000-00007
[35] T. Nomura, J. L. Katz, M. P. Power and C. Saito, “Evaluation of the Micromechanical Elastic Properties of Potential Bone-Grafting Materials,” Journal of Biomedical Materials Research Part B, Vol. 73, No. 1, 2005, pp. 29-34.
[36] B. B. Hole, J. A. Schwarz, J. L. Gilbert and B. L. Atkinson, “A Study of Biologically Active Peptide Sequences (P-15) on the Surface of an ABM Scaffold (PepGen P-15®) Using AFM and FTIR,” Journal of Biomedical Materials Research Part A, Vol. 74, No. 4, 2005, pp. 712-721. doi:10.1002/jbm.a.30331
[37] D. Turhani, C. Item, D. Thurnher, D. Kapral, B. Cvikl, M. Weissenbock, K. Yerit, B. Erovic, D. Moser, F. Watzinger, R. Ewers and G. Lauer, “Evidence of Osteocalcin Expression in Osteoblast Cells of Mandibular Origin Growing on Biomaterials with RT-PCR and SDS-PAGE/ Western Blotting,” Mund-, Kieferund Gesichtschirurgie, Vol. 7, No. 5, 2003, pp. 294-330. doi:10.1007/s10006-003-0495-7
[38] S. J. Froum, D. P. Tarnow, S .S. Wallace, M. D. Rohrer and S. C. Cho, “Sinus Floor Elevation Using Anorganic Bovine Bone Matrix (Osteograph®/N) with and without Autogenous Bone: A Clinical, Histologic, Radiographic, and Histmorphometric Analysis,” International Journal of Periodontics & Restorative Dentistry, Vol. 18, No. 6, 1998, pp. 528-543.
[39] A. Sogal and A. J. Tofe, “Risk Assessment of Bovine Spongiform Encephalopathy Transmission through Bone Graft Material Derived from Bovine Bone Used for Dental Applications,” Journal of Periodontology, Vol. 70, No. 9, 1999, pp. 1053-1063. doi:10.1902/jop.1999.70.9.1053
[40] E. W. D. Huffman and R. L. Keil, “Determination of Trace Organic Carbon and Nitrogen in the Presence of Carbonates in Anorganic Bovine Bone Graft Materials,” Microchemical Journal, Vol. 74, No. 3, 2003, pp. 249-256. doi:10.1016/S0026-265X(03)00031-6
[41] F. Carinci, F. Pezzetti, S. Volinia, G. Laino, D. Arcelli, E. Caramelli, M. Degidi and A. Piatelli, “P-15 cell Binding Domain Derived from Collagen: Analysis of MG63 Osteoblastic-Cell Response by Means of a Microarray Technology,” Journal of Peri-odontology, Vol. 75, No. 1, 2004, pp. 66-83. doi:10.1902/jop.2004.75.1.66
[42] M. Ueda, I. Tohnai and H. Nakai, “Tissue Engineering Research in Oral Implant Surgery,” Artificial Organs, Vol. 25, No. 3, 2001, pp. 164-171. doi:10.1046/j.1525-1594.2001.025003164.x
[43] T. Hanks and B. L. Atkinson, “Comparison of Cell Viability on Anorganic Bone Matrix with or without P-15 Cell Binding Peptide,” Biomaterials, Vol. 25, No. 19, 2004, pp. 4831-4836. doi:10.1016/j.biomaterials.2003.12.007
[44] A. Kubler, J. Neugebauer, J. H. Oh, M. Scheer and J. E. Zoller, “Growth and Proliferation of Human Osteoblasts on Different Bone Graft Substitutes: An in Vitro Study,” Implant Dentistry, Vol. 13, No. 2, 2004, pp. 171-179. doi:10.1097/01.ID.0000127522.14067.11
[45] A. Scarano, G. Iezzi, G. Petrone, G. Orsini, M. Degidi, R. Strocchi and A. Piatelli, “Cortical Bone Regeneration with PepGen P-15®: A Histological and Histomorphometric Pilot Study in Rabbits,” Implant Dentistry, Vol. 12, No. 4, 2003, pp. 318-324. doi:10.1097/01.ID.0000095467.48241.68
[46] M. Thorwarth, S. Schultze-Mosgau, F. Wehrhan, P. Kessler, S. Srour, J. Wiltfang and K. A. Schlegel, “Bioactivation of an Anorganic Bone Matrix by P-15 Peptide for the Promotion of Early Bone Formation,” Biomaterials, Vol. 26, No. 28, 2005, pp. 5648-5657. doi:10.1016/j.biomaterials.2005.02.023
[47] S. Hofman, M. Sidqui, D. Abensur, P. Valentini and P. Missika, “Effects of Laddec on the Formation of Calcified Bone Matrix in Rat Calvariae Cells Culture,” Biomaterials, Vol. 20, No. 13, 1999, pp. 1155-1166. doi:10.1016/S0142-9612(97)00082-3
[48] G. Orsini, T. Traini, A. Scarano, M. Degidi, V. Perrotti, M. Piccirilli and A. Piattelli, “Maxillary Sinus Augmentation with Bio-Oss®: A Light, Scanning, and Transmission Electron Microscopy Study in Man,” Journal of Biomedical Materials Research Part B, Vol. 74, 2005, pp. 448-457.
[49] J. Hemmerlé, F. J. Cuisinier, P. Schultz and J.- C. Voegel, “HRTEM Study of Biological Crystal Growth Mechanisms in the Vicinity of Implanted Synthetic Hydroxyapatite Crystals,” Journal of Dental Research, Vol. 76, No. 2, 1997, pp. 682-687. doi:10.1177/00220345970760020901
[50] G. Daculsi, R.Z. LeGeros, E. Nery, K. Lynch and B. Kerebel, “Transformation of Biphasic Calcium Phosphate Ceramics in Vivo: Ultrastructural and Physicochemical Characterization,” Journal of Biomedical Materials Researc, Vol. 23, No. 8, 1989, pp. 883-894. doi:10.1002/jbm.820230806
[51] M. D. McKee and A. Nanci, “Ultrastructural, Cytochemical and Immunocytochemical Studies on Bone and Its Interfaces,” Cell Mater, Vol. 3, 1993, pp. 219-243.
[52] M. McKee and A. Nanci, “Osteopontin at Mineralized Tissue Interfaces in Bone, Teeth and Osseointegrated Implants: Ultrastructural Distribution and Implications for Mineralized Tissue Formation, Turnover and Repair,” Microscopy Research and Technique, Vol. 33, No. 2, 1996, pp. 141-164. doi:10.1002/(SICI)1097-0029(19960201)33:2<141::AID-JEMT5>3.0.CO;2-W
[53] V. B. Rosen, L. W. Hobbs and M. Spector, “The Ultrastructure of Anorganic Bovine Bone and Selected Synthetic Hyroxyapatites Used as Bone Graft Substitute Materials,” Biomaterials, Vol. 23, No. 3, 2002, pp. 921-928. doi:10.1016/S0142-9612(01)00204-6
[54] F. I. Tapety, N. Amizuka, K. Uoshima, S. Nomura and T. Maeda, “A Histological Evaluation of the Involvement of Bio-Oss® in Osteoblastic Differentiation and Matrix Synthesis,” Clinical Oral Implants Research, Vol. 15, No. 3, 2004, pp. 315-324. doi:10.1111/j.1600-0501.2004.01012.x.

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