Maxillary sinus floor augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement

Transcription

1 Maxillary sinus floor augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement Hyeon-Jung Lee, DDS, a Byung-Ho Choi, DDS, PhD, b Jae-Hyung Jung, DDS, a Shi-Jiang Zhu, MD, c Seoung-Ho Lee, DDS, PhD, d Jin-Young Huh, DDS, a Tae-Min You, DDS, a Jingxu Li, DDS, c Seoul and Wonju, South Korea YONSEI UNIVERSITY, WONJU COLLEGE OF MEDICINE, AND EWHA WOMAN S UNIVERSITY Objective. The aim of this study was to evaluate the use of autogenous bone in combination with platelet-enriched fibrin glue as a grafting material for maxillary sinus augmentation with simultaneous implant placement in dogs. Study design. The mucous membranes of 12 sinuses in 6 dogs were elevated bilaterally. In the right sinus, autogenous bone mixed with platelet-enriched fibrin glue was grafted into the space between the membrane and the sinus wall. In the left sinus, autogenous bone alone was grafted as a control. At the same time, 2 dental implants were inserted into the grafting material through the maxillary sinus floor. The animals were killed 6 months after surgery. Results. The mean bone-implant contact was 40.5% on the fibrin glue side and 32.3% on the control side (P.05). The mean height of newly formed bone in the augmented area was 12.2 mm on the fibrin glue side and 10.7 mm on the control side (P.05). Conclusion. The results indicate that the use of autogenous bone mixed with platelet-enriched fibrin glue can achieve results superior to those for grafts of autogenous bone alone. The specific improvements of this technique include enhanced osseointegration of dental implants and increased height of new bone. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:329-33) In the posterior maxilla, implant placement may be problematic because the alveolar process tends to resorb with age, while the maxillary sinus becomes larger. As there is little available bone volume in this region, sinus floor elevation has become an important procedure in preimplant grafting. 1 Although several materials are available for sinus grafting, autogenous bone is often the first choice because of its osteoinductive potential, compatibility, and satisfactory clinical results. 2,3 There is currently a great deal of interest in oral and maxillofacial bone grafting procedures that involve the use of platelet-enriched fibrin glue to enhance bone This work was supported by grant No. R from the Medical Science and Engineering Research Program of the Korean Science and Engineering Foundation. a Graduate, Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, South Korea. b Professor, Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University (Brain Korea 21 Project for Medical Sciences), Seoul, South Korea. c Research Assistant, Department of Dentistry, Yonsei University, Wonju College of Medicine, Wonju, South Korea. d Associate Professor, Department of Periodontology, Ewha Woman s University, Seoul, South Korea. Received for publication Dec 5, 2005; returned for revision Feb 20, 2006; accepted for publication Mar 17, /$ - see front matter 2007 Mosby, Inc. All rights reserved. doi: /j.tripleo formation and increase the rate of bone graft healing. The fibrin glue improves bone graft incorporation by physically holding the bone particles firmly together. 4 In addition to the physical benefits, the incorporation of platelets into the fibrin glue 4,5 also accelerates the bone graft healing process through the release of numerous different growth factors from the platelets upon activation with thrombin. 6 Previous studies have shown that a combination of platelet-enriched fibrin glue and autogenous bone grafting can increase the rate of osteogenesis and enhance bone formation. 4,5 The aim of this study was to evaluate the combined use of autogenous bone and platelet-enriched fibrin glue as a grafting material for maxillary sinus augmentation with simultaneous implant placement in dogs. MATERIAL AND METHODS Animal model Six adult female mongrel dogs (15 to 20 kg body weight) were used in this experiment. The protocol was approved by the Animal Care and Use Committee, Yonsei Medical Center, Seoul, Korea. Platelet-enriched fibrin glue preparation Platelet-enriched fibrin glue was prepared using a previously described technique. 5 Briefly, 20 ml autologous blood from each dog was treated as described to separate platelet-rich plasma (PRP) from the blood. The 329

2 330 Lee et al. March 2007 fibrinogen solution was subsequently prepared using the PRP. A quantity of 240 L of transexamic acid and 900 L ethanol were added to 7.5 ml PRP and incubated in an ice water bath for 20 to 30 minutes. The precipitated fibrinogen was separated by centrifugation at 3000g for 8 minutes at 0 to 4 C. After discarding the supernatant, the fibrinogen precipitate was re-dissolved at 37 C and diluted to 50% with 0.9% NaCl. A thrombin solution was prepared using the remaining PRP. Briefly, 2.5 ml PRP was added to 22.5 ml citric acid, and the mixture was centrifuged at 3000g for 5 minutes at 4 C. After discarding the supernatant, the precipitate was dissolved in 150 L CaCl 2 (0.1 M) and the ph was adjusted to 7 by the addition of 100 L NaHCO 3. After clot formation, the thrombin solution was collected and diluted to 10% with 0.05 M CaCl 2. The fibrin glue was prepared by mixing the fibrinogen and thrombin solutions in a3:1 (vol/vol) ratio. Thorn et al. 5 reported that autologous fibrin glue prepared with this technique contains high platelet and fibrinogen concentrations. Surgical procedure All surgical procedures were performed under systemic anesthesia (ketamine, 5 mg/kg and xylazine, 2 mg/kg IM). The maxillary premolars and first molar of each dog had been previously extracted bilaterally, and the ridges had been allowed to heal for 3 months. Before implantation, a block-type bone graft was harvested from the iliac crest. The whole graft was ground with a bone mill (Leibinger, Freiburg, Germany) and the bone graft was stored in a physiologic saline solution. Based on the technique described by Kent and Block, 7 the sinus floor elevation procedure was performed identically on both sides of each dog, except for the addition of the platelet-enriched fibrin glue at the test site. The edentulous region was opened by crestal incision. The mucoperiosteal flap was reflected on the buccal cortical plate, extending from the first maxillary premolar to the second maxillary molar. A bone window of 1 2cm 2 was created with a burr, taking care to avoid perforation of the antral membrane. The sinus membrane was elevated from the maxillary sinus floor. After creating the extrasinusoidal space, the bone of the maxillary sinus floor was reduced to a thickness of 5 mm for standardization. In the right sinus, the resultant space between the membrane and the sinus floor was filled with a mixture of particulate bone and platelet-enriched fibrin glue. In the left sinus, particulate autogenous bone was used alone for the control side. Two dental implants (length, 10 mm; diameter, 4.1 mm; Osstem, Seoul, Korea) were then placed in the grafting material bilaterally through the maxillary sinus floor (Fig. 1). Finally, the mucoperiosteal flap was repositioned and sutured. Fig. 1. View of the implant and autogenous bone mixed with platelet-enriched fibrin glue immediately after placement in the space between the sinus membrane and the sinus floor. Sample preparation Animals were killed 6 months after surgery and the bone blocks with the implants were excised. Resected bone specimens were fixed in 10% buffered formalin and embedded in methylmethacrylate resin. Blocks were cut along the frontal longitudinal axis of the implants. Histological sections (40 m) were prepared using a cuttinggrinding method and were stained with toluidine blue. Histomorphometry A morphometric study using an image analysis system (IBAS, Contron, Erching, Germany) was performed to quantify the newly formed bone around the implants. The bone-to-implant contact (BIC), defined as the length of bone surface border in direct contact with the implant perimeter ( 100%), was then calculated. In addition, the height of newly formed bone in the augmented area, defined as the maximal height of bone in the palatal side of the implant, was measured. Statistical analysis Wilcoxon s-signed rank test for paired samples was used to calculate statistical differences between the 2 sides. RESULTS All animals recovered rapidly from surgery and were healthy throughout the follow-up, with no indication of infection or other complications. On gross examination of both sinuses, the sinus membrane was intact and flush with the apical implant surface and the original graft volume was clearly reduced. The newly formed bone was more abundant on the fibrin glue side than on the control side (Fig. 2). Histological examination showed that all of the implants were surrounded by bone except the apical implant

3 Volume 103, Number 3 Lee et al. 331 Fig. 2. Photograph of the maxillary sinuses showing the augmented area and the implant; S, maxillary sinus cavity. A, Control side. B, Fibrin glue side. Fig. 3. View of the histologic sections of the specimen showing the augmented area and the implant. A, Control side. B, Fibrin glue side. surface in both sinuses, which was covered by bundles of collagen fibers and the adjacent respiratory mucosa (Fig. 3). The mucous membrane overlying the apical implant portion did not contain mucous glands. The mean percentages of direct implant-bone contact in both groups are shownintablei.thequantitativemorphometricanalysis showed significantly more bone/implant contact in the fibrin glue group; the BIC was 32.3% 12.0% for the control group and 40.5% 14.4% for the fibrin glue group (P.05). The height of newly formed bone in the augmented area was mm for the control group and mm for the fibrin glue group; this difference was also statistically significant (P.05). Thus, the fibrin glue group demonstrated significantly better bone formation than the control group. DISCUSSION This study investigated the effectiveness of autogenous bone grafts and platelet-enriched fibrin glue in maxillary sinus augmentation in dogs. Results showed that when a combination of autogenous bone and platelet-enriched fibrin glue was used for sinus grafting, the volume of the new bone formed was significantly greater than in the group treated with autogenous bone alone. In addition, the percentage of direct implantbone contact was significantly higher in the fibrin glue group than in the group treated with autogenous bone grafts alone. This suggests that the efficiency of autogenous bone grafting can be improved by the addition of platelet-enriched fibrin glue. Thorn et al. 5 reported that the concentration of fibrinogen in platelet-enriched fibrin glue was approximately 12 times that found in PRP, and that the concentration of growth factors (as measured by platelet-derived growth factor) was approximately 8 times that seen in PRP. In this study, platelet-enriched fibrin glue with high concentrations of platelets and fibrinogen was prepared using the technique described by Thorn et al. 5 Fibrin glues were first used to establish hemostasis at the beginning of the last century. In 1940, Young and Medawar 8 mixed bovine thrombin with plasma fibrinogen to produce the first biologic adhesive. Several commercial fibrin glues are now available; however, these products have risk factors of viral transmission and allergic response Moreover, they do not contain a high concentration of platelets, unlike the fibrin glue prepared using the technique described here. The fibrin glue used in this study offers significant benefits over conventional glues in that it can accelerate wound healing, a process aided by high concentrations of growthfactorsinplatelets Growthfactorsreleased from the platelets have been shown to include plateletderived growth factor, transforming growth factor, platelet-derived epidermal growth factor, platelet-derived angiogenesis factor, insulin-like growth factor 1, and platelet factor 4. 15,16 These growth factors, either alone or in combination, are known to promote cell proliferation, cell differentiation, motility, and matrix synthesisbybindingtospecificcellsurfacereceptors. 17 It is likely that growth factors released from the platelets, including bone morphogenetic protein (BMP)-2, might interact with neighboring mesenchymal stem cells to induce proliferation and differentiation into osteoblasts, subsequently forming new bone. More basic research investigating the mechanism by which this occurs is clearly necessary in order to capitalize on the ability of growth factors to enhance bone formation in vivo. The benefits of platelet-enriched fibrin glue on BIC have not previously been reported. In the present study, the BIC achieved 6 months following platelet-enriched fibrin glue application was 40.5%, compared with 32.3% in the absence of platelet-enriched fibrin glue. BMPs were previously shown to be effective in enhanc-

4 332 Lee et al. March 2007 Table I. Parameters (mean value and standard deviation) of BIC and bone formation 6 months after sinus augmentaiton with autogenous bone combined with platelet-rich fibrin glue and primary insertion of a titanium implant Autogenous bone/autofibrin Autogenous bone P values Bone-implant contact, % Height of newly formed bone in the augmented area, mm ing the osseointegration of dental implants. 18,19 Lynch et al. 17 demonstrated astatistically significant enhancement of the BIC after the application of rhpdgf and rhigf-i. The positive effect of growth factors on osseointegration suggests that the growth factors contained in platelet-enriched fibrin glue may have enhanced a peri-implant bone reaction in our study. In the present study, all augmented areas showed a clear tendency for resorption regardless of whether the bone graft was treated with platelet-enriched fibrin glue or not. This type of resorption has been described in the literature 20 andisaspecificdisadvantageofconventionalbone grafting techniques. In this study, however, it was possible to reduce the resorptive process in bone grafts by using platelet-enriched fibrin glue. The height of newly formed bone on the sinus floor 6 months after surgery was 12.0 mm in the presence of platelet-enriched fibrin glue, which corresponded to the total height of the implant. In the absence of platelet-enriched fibrin glue, this value was 10.7 mm. This represents a significant difference between the 2 sides. Future studies are required to determine whether the observed enhancement of the bone height can be maintained over the long term, as it is important to recognize that the trabecular bone area will undergo continuous remodeling in response to mechanical and endocrine influences. 21 To our knowledge, this is the first report concerning the influence of platelet-enriched fibrin glue on BIC and the height of newly formed bone in maxillary sinus augmentation with simultaneous implant placement. Platelet-enriched fibrin glue improved both the osseointegration of dental implants and the bone height in the regenerated sinus bone 6 months after surgery. Our data support the concept that platelet-enriched fibrin glue, in combination with autogenous bone, may be effective in improving the height of new bone and the osseointegration of dental implants in sinus floor augmentation with simultaneous implant placement. REFERENCES 1. Kahnberg KE, Ekestubbe A, Grondahl K, Nilsson P, Hirsch JM. Sinus lifting procedure. I. One-stage surgery with bone transplant and implants. Clin Oral Impl Res 2001;12: Pejrone G, Lorenzett M, Mottati M, Valente G, Schierano GM. Sinus floor augmentation with autogenous iliac bone block grafts: a histological and histomorphometrical report on the two-step surgical technique. Int J Oral Maxillofac Surg 2002;31: Peleg M, Garg AK, Misch CM, Mazor Z. Maxillary sinus and ridge autmentations using a surface-derived autogenous bone graft. J Oral Maxillofac Surg 2004;62: Tayapongsak P, O Brian DA, Monteiro CB, Arceo-Diaz LY. Autologous fibrin adhesive in mandibular reconstruction with particulate cancellous bone and marrow. J Oral Maxillofac Surg 1994;52: Thorn JJ, Sørensen H, Weis-Fogh U, Andersen M. Autologous fibrin glue with growth factors in reconstructive maxillofacial surgery. Int J Oral Maxillofac Surg 2004;33: Ross R, Raines EW, Bowen-Pope DF. The biology of plateletderived growth factor. Cell 1986;46: Kent JN, Block MS. Simultaneous maxillary sinus floor bone grafting and placement of hydroxylapatite-coated implants. J Oral Maxillofac Surg 1989;47: Young JZ, Medawar PB. Fibrin suture of peripheral nerves. Lancet 1940;1: Kjaergard HK, Trumbull HR. Vivostat system autologous fibrin sealant: preliminary study in elective coronary bypass grafting. Ann Thorac Surg 1998;66: Nichols WL, Daniels TM, Fisher PK, Owen WG, Pineda AA, Mann KG. Antibodies to bovine thrombin and coagulation factor V associated with surgical use of topical bovine or fibrin glue : a frequent finding. Blood 1993;82: Tock B, Drohan W, Hess J, Pusateri A, Holcomb J, Macphee M. Haemophilia and advanced fibrin sealant technologies. Haemophilia 1998;4: Miyazono K, Takaku F. Platelet-derived growth factors. Blood Rev 1989;3: Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem 1991;45: Whitman DH, Berry RL, Green DM. Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997;55: Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants 2003;18: Ganio C, Tenewitz FE, Wilson RC, Maules BG. The treatment of chronic nonhealing wounds using autologous platelet-derived growth factors. J Foot Ankle Surg 1993;32: Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound healing. J Clin Invest 1989;84: Bessho K, Cames DL, Cavin R, Chen HY, Ong JL. BMP stimulation of bone response adjacent to titanium implants in vivo. Clin Oral Impl Res 1999;10: Terheyden H, Jepsen S, Möller B, Tucker MM, Rueger D. Sinus floor augmentation with simultaneous placement of dental implants using a combination of deproteinized bone xenograft and recombinant human osteogenetic protein-1: a

5 Volume 103, Number 3 Lee et al. 333 histometric study in miniature pigs. Clin Oral Impl Res 1999; 10: Hatano N, Shimizu Y, Olya K. A clinical long-term radiographic evaluation of graft height changes after maxillary sinus floor augmentation with a 2:1 autogenous bone/xenograft mixture and simultaneous placement of dental implants. Clin Oral Impl Res 2004;15: Schmitz JP, Hollinger JO. The biology of platelet rich plasma. J Oral Maxillofac Surg 2001;59: Reprint requests: Byung-Ho Choi, DDS, PhD Department of Oral and Maxillofacial Surgery Wonju Christian Hospital Yonsei University 162 Ilsan-Dong, Wonju Kangwon-Do, South Korea choibh@wonju.yonsei.ac.kr