|Year : 2012 | Volume
| Issue : 2 | Page : 172-179
Bone resorption analysis of platelet-derived growth factor type BB application on collagen for bone grafts secured by titanium mesh over a pig jaw defect model
Alan Scott Herford1, Marco Cicciù2
1 Department of Oral and Maxillofacial Surgery, Loma Linda University, Loma Linda, CA, USA
2 Department of Human Pathology, University of Messina School of Dentistry, Messina, ME, Italy
|Date of Web Publication||4-May-2013|
Department of Human Pathology, Dental School, Messina University, Via Consolare Valeria 98100, Messina
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Purpose: The aim of this investigation was to evaluate whether the addition of the platelet derived growth factor type BB (PDGF-BB) to a collagen matrix applied on a titanium mesh would favor healing and resorption onto the grafted bone. A histologic and radiographic study of two different groups (test and control) was performed. Designs: A surgical procedure was performed on 8 pigs to obtain 16 bilateral mandibular alveolar defects. All the defects were then reconstructed with a mixture of autogenous bovine bone using titanium mesh positioning. Two groups, with a total of 16 defects were created: The first to study collagen sponge and PDGF-BB and the second to control collagen only. The collagen matrix was positioned directly over the mesh and soft tissue was closed without tensions onto both groups without attempting to obtain primary closure. Possible exposure of the titanium mesh as well as the height and volume of the new bone was recorded. Results: New bone formation averaged about 6.68 mm in the test group studied; the control group had less regenerated bone at 4.62 mm. Conclusion: PDGF-BB addition to the collagen matrix induced a strong increase in hard and soft tissue healing and favored bone formation, reducing bone resorption even if the mesh was exposed.
Keywords: Bone tissue, collagen, growth factors, platelet-derived growth factor type BB
|How to cite this article:|
Herford AS, Cicciù M. Bone resorption analysis of platelet-derived growth factor type BB application on collagen for bone grafts secured by titanium mesh over a pig jaw defect model. Natl J Maxillofac Surg 2012;3:172-9
|How to cite this URL:|
Herford AS, Cicciù M. Bone resorption analysis of platelet-derived growth factor type BB application on collagen for bone grafts secured by titanium mesh over a pig jaw defect model. Natl J Maxillofac Surg [serial online] 2012 [cited 2020 Jul 4];3:172-9. Available from: http://www.njms.in/text.asp?2012/3/2/172/111374
| Introduction|| |
Loss of teeth and alveolar bone can adversely affect the patient's speech as well as their ability to masticate. Surgical resection and traumatic injuries can deprive patients of adequate hard and soft tissue support for dentures and make the placement of dental implants much more difficult. Dental implants are effective in replacing missing teeth only when the underlying osseous foundation is adequate in size, volume, and quality. Unfortunately, many patients lack sufficient bone height and/or width to provide the needed support, and as a result, denture support and dental restorations are compromised. The lack of teeth and alveolar bone often leads to further resorption which can progress to severe bony deficits of the maxilla and mandible. Several bone-grafting techniques have been developed to correct bony deficiencies with varying degrees of success. Some of the more common technique includes autogenous bone harvested from the patient's iliac crest, tibia, mandible, or maxillary tuberosity. When autogenous bone grafting techniques are considered the gold standard, they do carry limitations including surgical complications, cost, and patient morbidity associated with harvesting bone. ,,,,,,,,
Multiple surgical approaches using graft materials from a variety of sources have been recommended to facilitate subsequent dental implants placement. Of note among these methodologies are the following: On-lay bone grafts, ridge splitting, sub-periosteal membrane-guided regeneration, alveolar osteotomies/sandwich grafts, inter-positional grafts, mandibular inferior border grafting, maxillary sinus floor grafting, grafting overexposed threads, distraction osteogenesis, and the use of growth factors. These adjunctive surgical procedures are performed to allow/facilitate implant placement and get superior clinical results. ,,,,,,,,
To replace missing bone prior to dental implant placement patients require grafting. As a result of this, often there is insufficient soft tissue to cover the bone graft completely. Adjacent tissues can be used to achieve tension-free closure but the process disrupts the normal soft tissue architecture, resulting in a decrease or obliteration of the vestibule. Consequently, when the bone graft heals, soft tissue grafting may also be required to reposition and re-establish the correct vestibular architecture. ,,
Free connective tissue grafts or split thickness skin grafts are commonly used to increase vestibular depth. Being effective in recreating depth and size, autogenous soft tissue transplants can result in donor site morbidity such as prolonged pain, swelling, infection, numbness, and bleeding. Healing of the donor site can take from 6 to 8 weeks, making surgical options less desirable. ,
Insufficient keratinized gingiva adjacent to dental implants is another frequently occurring clinical indication for soft tissue grafting. Treatment options include free connective tissue grafts, xenogeneic grafts, or allogeneic materials, each having its own set of advantages and disadvantages. A common problem with many of these grafting techniques is contracture at the extended surgical area and mucosal-surface scarring. An ideal autogenous-substituting graft would heal rapidly with little contracture or granulation tissue formation, promote homeostasis, resist infection, and cause the patient less pain by eliminating the need of a second surgical site. ,,,,,
The purpose of this investigation is to compare collagen matrix application with and without platelet-derived growth factor type BB (PDGF-BB) to control bone healing and resorption over an intra-oral bone created defect in pigs. The excellent stimulatory effects of PDGF-BB as a chemo-attractant and mitogen, along with its ability to promote angiogenesis, indicate it as a key mediator in tissue repair, which improves soft tissue healing over a bone graft.
This study also wanted to determine whether the addition of the PDGF to the collagen would improve hard and soft tissue healing over particulated bone grafts by inducing less bone resorption even when the titanium mesh is exposed.
| Materials and Methods|| |
Note: This study has been approved by the Loma Linda University Ethical Committee.
Eight, 26-week-old micro-pigs underwent a surgical procedure to create bilateral mandibular defects, for a total of 16 defects. The created defects reflected the Class V or VI of Cawood and Howell's classification, having vertical and horizontal components of resorption.  Extraction of right and left mandibular posterior teeth with simultaneous osteotomy followed by a healing time of 4 weeks was performed. Each defects was about 30 mm × 20 mm, carried out on the pigs' posterior mandible, and PA digital radiographs of each defect were obtained.
Test group: Collagen + PDGF: BB - 8 sites. Control group: Collagen only - 8 sites. Each pig had its mouth divided into two halves; each half had a test and the control group assigned to it. Three months after the first surgery, the pigs were scheduled for the second reconstructive surgery. Guided bone regeneration technique, using titanium mesh, was carried out on the tridimensially reconstruction of the created defects. A collagen matrix was applied to cover the bone graft and mesh, then the soft tissue was closed. Radiograph investigation of the reconstructed bone was performed to control the position of the mesh [Figure 1].
|Figure 1: Mandibular defects created for the next implantation of the bone graft|
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The collagen used for the study was Mucograft® , a sponge matrix developed by Geistlich Pharma, Wolhusen, Switzerland in 2006 as a bio-resorbable matrix and was US Food and Drug Administration (FDA) approved for soft tissue regeneration in oral surgery. This product was made from porcine type I and III collagen and consisted of two functional layers: A smooth collagen layer is a compact structure and a porous layer. Depending on the treated surgical site, the material biodegraded within 3-10 weeks. Research has shown that the biodegradation of the product occurs with very little, if any, inflammatory cellular response. ,,
During the reconstructive surgery, a horizontal supra-crestal muco peri-osteal flap was elevated in the mandibular mucosa, extending to the periosteum overlying the defect. The incision was carried out on the alveolar ridge of the defect. Following visualization of the defect, a surgical stent was used to remove bone and a standardized 20 mm × 30 mm defect was created. Approximately 5 cc of bone was removed and then combined with 5 cc of deproteinized bovine bone particles. A titanium mesh model of the defect was created and then secured in place to prevent mobility of the graft during the healing process. The surgical site was then closed.
For both groups, collagen was placed over the titanium mesh. The mucosa was sutured without stretching the tissue and incomplete closure with exposure of some of the collagen matrix was performed. The collagen matrix in the test group was saturated with 2.5 ml of (0.3 mg/ml) of PDGF-BB (GEM 21S® Osteohealth Company Shirley, NY, USA) (0.75 mg) [Figure 2], [Figure 3], [Figure 4] and [Figure 5].
|Figure 3: Collagen soaked with platelet derived growth factor type BB application|
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The recombinant human Platelet Derived Growth Factor type BB (rhPDGF-BB) provided the biological input for tissue repair by increasing angiogenesis and the proliferation of osteoblasts. This specific cytokine stimulated chemotaxis proliferation, a new gene expression in monocytes-macrophages and fibroblasts. It also increased tissue repair process, favored soft tissue and bony wound healing and when delivered exogenously, stimulated collagen production, improved wound strength, and initiated callous formation. , Moreover, rhPDGF-BB can easily be transmitted into a collagen carrier.
Following 3 months of healing, the pigs were humanely euthanized and radiographs of the grafted sites were taken. Histologic sections of bone and soft tissue were prepared and analyzed. The specimens were fixed in neutral buffered 10% formalin, dehydrated and infiltrated in resin, and then embedded and polymerized in resin blocks. The blocks were cut and ground using the Exakt-cutting-grinding system to a thickness of 50 μm and stained with Mayer's hematoxylin and eosin or Masson's Trichrome stain. Histological evaluation included searching for any residual matrix as well as any evidence of inflammation. The quantity of the grafted bone was also evaluated. Qualitative and quantitative histological evaluations of soft-tissue ingrowth and bone regeneration were performed on non-decalcified grounded sections. For statistical analysis, the Mann-Whitney-Wilcoxon test, the Kruskal-Wallis, and the paired t-test were applied. P values were adjusted using the Dunnett-Hsu adjustment [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13] and [Figure 14].
|Figure 6: Clinical exposure of the mesh at the time of the pig's euthanasia|
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|Figure 9: Mayer's hematoxylin and eosin investigation of the test group section. Anterior section|
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|Figure 10: Mayer's hematoxylin and eosin investigation of the test group section. Posterior section|
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|Figure 11: Masson's Trichrome stain investigation of the test group section|
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|Figure 12: Mayer's hematoxylin and eosin investigation of the control group section. Anterior section|
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|Figure 13: Mayer's hematoxylin and eosin investigation of the control group section. Posterior section|
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|Figure 14: Masson's Trichrome stain investigation of the control group section|
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| Results|| |
The amount of bone formation and incidence of graft exposures were evaluated [Table 1]. The areas of regenerated tissue were randomly selected per section [Figure 15].
|Table 1: Bone resorption and mesh exposure in the test and control groups|
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The height of new bone was measured in separate sections. The height was reported as an average by measuring the distance from the non-grafted bone to the crest of the regenerated ridge. For the test group, the average of new bone formation was 6.68 mm whereas the Control group had an average less at 4.62 mm. Exposure of the titanium mesh occurred postoperatively for the majority of the pigs. In this animal study the exposure rate was test group - 50% and control group - 100%.
| Discussion|| |
In recent years, research to investigate bone resorption of autogenous/homologous/xenogeneic block grafts used for oral and maxillofacial surgery has been performed. Some investigations reported how in the 1 st year after reconstructive surgery, the bone graft resorption is significant and may progress in the following years.  Other studies clearly demonstrated that simple appositioning of a cortico-cancellous bone graft over the mandibular buccal cortex for augmentation of the alveolar ridge is a non-predictable method to increase ridge volume. The maintenance of the autogenous bone grafts may be influenced by several parameters such as embryological origin, architecture, orientation, and the nature and dimension of the graft.
However, some alveolar defects, particularly in reference to Cawood and Howell classes V and VI,  require bone grafting prior to dental implants placement. These clinical situations offer insufficient soft tissue to completely cover the bone graft without aggressively stretching the adjacent tissue. This adverse condition may determine significant bone resorption due to exposure of the grafted materials over a very short period therefore the previous regenerative surgery will fail. ,,
The advantages of using autograft bone, the treatment of choice or "gold standard" for skeletal reconstruction, are small due to limited tissue resources and donor morbidity. Pre-clinical studies have shown that growth factors induce normal autogenous bone in clinically relevant defects in the craniofacial skeleton, thereby favoring hard and soft tissue healing. The newly formed bone assumes characteristics of the adjacent resident bone and allows placement, osseointegration, and functional loading of dental implant. ,,,,,
The results of this study, along with other recent investigations into the application of growth factors in bone regeneration techniques clearly underlined how the cytokine implanted on the carrier can accelerate the healing process. , Moreover, collagen carriers may improve soft tissue volume over the graft by inducing less incidence of bone graft exposure. ,
Many biomaterials have been used as a biological barrier in the past to cover the grafts, allowing growth of host epithelial cells beneath the bone. Kim et al. reported that a double layer collagen membrane positioned over the bone graft  is helpful for the integration of the onlay block bone graft. An animal study performed by Thoma, et al. evaluated the effectiveness of a synthetic, biodegradable membrane made of polyethylene glycol. In that study, the placing of the biodegradable membrane successfully prevented collapse of the covering soft tissues protecting the graft. 
The collagen material used in this study (Mucograft® ) is a bio-resorbable, bilayer matrix collagen used instead of soft tissue. Recent clinical studies have demonstrated how this collagen matrix® can be applied to increase both keratinized and non-keratinized mucosa with rapid degradation and healing process. ,, This study results showed that the addition of a PDGF to collagen® improved soft tissue healing, and therefore reduced mesh exposure and protected the grafted bone.
PDGF is a naturally occurring cytokine that has been shown to be an excellent activator for mesenchymal origin cells. ,,,,,,,,
The use of rhPDGF-BB in combination with an osteo-conductive scaffold has been recently published in diverse papers connected to growth factors applied onto a carrier for periodontal regeneration. ,,,
The scientific base for this study is that PDGF stimulates angiogenesis, promotes cell migration in the bone defect from the surrounding tissue margins, and regulates cell proliferation. ,, The matrix, in addition to its role as a growth factor delivery vehicle, provides structural support for directing/recalling cells and helps the formation of new healing tissue.
The PDGF firstly acts by attracting neutrophils and macrophages and aiding in angiogenesis, chemotaxis, and mitogenesis. PDGF also regulates, Vascular endothelial growth factor (VEGF) further enhancing angiogenesis. Other growth factors like bone morphogenic proteins (BMPs) also play a role in chemotaxis and cell proliferation. However, those growth factors are primarily morphogenic. ,,
PDGF and BMPs regulate the controls for healing and regeneration of the bone tissue by repairing the tissue in case of bone fracture. From our study results, collagen combined with rhPDGF and maintains the volume of grafted bone and reduces bone resorption in case of mesh exposure. This may be due to improved soft tissue healing. Alternatively, it may be related to some osteo-induction activity of the growth factor. Literature, so far has different viewpoints regarding osteo-inductive properties of rhPDGF. It seems to induce proliferation more than morphogenesis. ,,
This study on pigs offers certain challenges about the post-operative compliance. Although the animals were maintained on a soft diet, they continued to chew on their metal cadges throughout the day. Exposure of the mesh was significantly higher in these animal specimens, which were clinically probable due to the above-mentioned factor. The exposure rates are as follows: Test group - 50%; control group - 100%. The rhPDGF test group showed significantly thicker soft tissue covering the bone graft. The clinical implications of the results are that there is no need for soft tissue grafting to cover the grafted site. Moreover, collagen membrane position allows tension-free closure over the bone graft. The addition of PDGF to the collagen® accelerates the soft tissue healing and promotes bone graft healing. The PDGF-BB added to the collagen ensures that the volume graft is maintained even if the mesh is exposed because it greatly enhances soft and hard tissue healing.
| References|| |
|1.||Watzek G, Weber R, Bernhart T, Ulm C, Haas R. Treatment of patients with extreme maxillary atrophy using sinus floor augmentation and implants: Preliminary results. Int J Oral Maxillofac Surg 1998;27:428-34. |
|2.||von Arx T, Wallkamm B, Hardt N. Localized ridge augmentation using a micro titanium mesh: A report on 27 implants followed from 1 to 3 years after functional loading. Clin Oral Implants Res 1998;9:123-30. |
|3.||Herford AS, Cicciù M. Recombinant human bone morphogenetic protein type 2 jaw reconstruction in patients affected by giant cell tumor. J Craniofac Surg 2010;21:1970-5. |
|4.||Simion M, Jovanovic SA, Tinti C, Benfenati SP. Long-term evaluation of osseointegrated implants inserted at the time or after vertical ridge augmentation. A retrospective study on 123 implants with 1-5 year follow-up. Clin Oral Implants Res 2001;12:35-45. |
|5.||Muhart M, McFalls S, Kirsner RS, Elgart GW, Kerdel F, Sabolinski ML, et al. Behavior of tissue-engineered skin: A comparison of a living skin equivalent, autograft, and occlusive dressing in human donor sites. Arch Dermatol 1999;135:913-8. |
|6.||Stellingsma C, Raghoebar GM, Meijer HJ, Batenburg RH. Reconstruction of the extremely resorbed mandible with interposed bone grafts and placement of endosseous implants. A preliminary report on outcome of treatment and patients› satisfaction. Br J Oral Maxillofac Surg 1998;36:290-5. |
|7.||Bedrossian E, Tawfilis A, Alijanian A. Veneer grafting: A technique for augmentation of the resorbed alveolus prior to implant placement. A clinical report. Int J Oral Maxillofac Implants 2000;15:853-8. |
|8.||Chen ST, Darby IB, Adams GG, Reynolds EC. A prospective clinical study of bone augmentation techniques at immediate implants. Clin Oral Implants Res 2005;16:176-84. |
|9.||Sailer HF. A new method of inserting endosseous implants in totally atrophic maxillae. J Craniomaxillofac Surg 1989;17:299-305. |
|10.||Zitzmann NU, Schärer P, Marinello CP. Long-term results of implants treated with guided bone regeneration: A 5-year prospective study. Int J Oral Maxillofac Implants 2001;16:355-66. |
|11.||Yerit KC, Posch M, Guserl U, Turhani D, Schopper C, Wanschitz F, et al. Rehabilitation of the severely atrophied maxilla by horseshoe Le Fort I osteotomy (HLFO). Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:683-92. |
|12.||Triplett RG, Nevins M, Marx RE, Spagnoli DB, Oates TW, Moy PK, et al. Pivotal, randomized, parallel evaluation of recombinant human bone morphogenetic protein-2/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation. J Oral Maxillofac Surg 2009;67:1947-60. |
|13.||Stoelinga PJ, Tideman H, Berger JS, de Koomen HA. Interpositional bone graft augmentation of the atrophic mandible: A preliminary report. J Oral Surg 1978;36:30-2. |
|14.||Jensen OT, Cullum DR, Baer D. Marginal bone stability using 3 different flap approaches for alveolar split expansion for dental implants: A 1-year clinical study. J Oral Maxillofac Surg 2009;67:1921-30. |
|15.||Duncan JM, Westwood RM. Ridge widening for the thin maxilla: A clinical report. Int J Oral Maxillofac Implants 1997;12:224-7. |
|16.||Keller EE, Tolman DE, Eckert SE. Maxillary antral-nasal inlay autogenous bone graft reconstruction of compromised maxilla: A 12-year retrospective study. Int J Oral Maxillofac Implants 1999;14:707-21. |
|17.||Wiltfang J, Schultze-Mosgau S, Nkenke E, Thorwarth M, Neukam FW, Schlegel KA. Onlay augmentation versus sinuslift procedure in the treatment of the severely resorbed maxilla: A 5-year comparative longitudinal study. Int J Oral Maxillofac Surg 2005;34:885-9. |
|18.||Block MS, Baughman DG. Reconstruction of severe anterior maxillary defects using distraction osteogenesis, bone grafts, and implants. J Oral Maxillofac Surg 2005;63:291-7. |
|19.||von Arx T, Cochran DL, Schenk RK, Buser D. Evaluation of a prototype trilayer membrane (PTLM) for lateral ridge augmentation: An experimental study in the canine mandible. Int J Oral Maxillofac Surg 2002;31:190-9. |
|20.||Speroni S, Cicciu M, Maridati P, Grossi GB, Maiorana C. Clinical investigation of mucosal thickness stability after soft tissue grafting around implants: A 3-year retrospective study. Indian J Dent Res 2010;21:474-9. |
|21.||Nowzari H, Slots J. Microbiologic and clinical study of polytetrafluoroethylene membranes for guided bone regeneration around implants. Int J Oral Maxillofac Implants 1995;10:67-73. |
|22.||Hürzeler MB, Kohal RJ, Naghshbandi J, Mota LF, Conradt J, Hutmacher D, et al. Evaluation of a new bioresorbable barrier to facilitate guided bone regeneration around exposed implant threads. An experimental study in the monkey. Int J Oral Maxillofac Surg 1998;27:315-20. |
|23.||Bessho K, Murakami K, Iizuka T. The use of a new bilayer artificial dermis for vestibular extension. Br J Oral Maxillofac Surg 1998;36:457-9. |
|24.||Hall HD, O'Steen AN. Free grafts of palatal mucosa in mandibular vestibuloplasty. J Oral Surg 1970;28:565-74. |
|25.||Cawood JI, Howell RA. A classification of the edentulous jaws. Int J Oral Maxillofac Surg 1988;17:232-6. |
|26.||Herford AS, Akin L, Cicciu M, Maiorana C, Boyne PJ. Use of a porcine collagen matrix as an alternative to autogenous tissue for grafting oral soft tissue defects. J Oral Maxillofac Surg 2010;68:1463-70. |
|27.||Sheridan RL, Tompkins RG. Skin substitutes in burns. Burns 1999;25:97-103. |
|28.||Dougherty WR, Chalabian JR. Skin substitutes. West J Med 1995;162:540-1. |
|29.||Murashita T, Nakayama Y, Hirano T, Ohashi S. Acceleration of granulation tissue ingrowth by hyaluronic acid in artificial skin. Br J Plast Surg 1996;49:58-63. |
|30.||Machens HG, Berger AC, Mailaender P. Bioartificial skin. Cells Tissues Organs 2000;167:88-94. |
|31.||Kirsner RS. The use of Apligraf in acute wounds. J Dermatol 1998;25:805-11. |
|32.||Sanz M, Lorenzo R, Aranda JJ, Martin C, Orsini M. Clinical evaluation of a new collagen matrix (Mucograft prototype) to enhance the width of keratinized tissue in patients with fixed prosthetic restorations: A randomized prospective clinical trial. J Clin Periodontol 2009;36:868-76. |
|33.||Rutkowski JL, Thomas JM, Bering CL, Speicher JL, Radio NM, Smith DM, et al. Analysis of a rapid, simple, and inexpensive technique used to obtain platelet-rich plasma for use in clinical practice. J Oral Implantol 2008;34:25-33. |
|34.||Louis PJ, Gutta R, Said-Al-Naief N, Bartolucci AA. Reconstruction of the maxilla and mandible with particulate bone graft and titanium mesh for implant placement. J Oral Maxillofac Surg 2008;66:235-45. |
|35.||Chaushu G, Mardinger O, Peleg M, Ghelfan O, Nissan J. Analysis of complications following augmentation with cancellous block allografts. J Periodontol 2010;81:1759-64. |
|36.||Kaspar DW, Laskin DM. The effect of porcine skin and autogenous epithelial grafts on the contraction of experimental oral wounds. J Oral Maxillofac Surg 1983;41:143-52. |
|37.||Kim SH, Kim DY, Kim KH, Ku Y, Rhyu IC, Lee YM. The efficacy of a double-layer collagen membrane technique for overlaying block grafts in a rabbit calvarium model. Clin Oral Implants Res 2009;20:1124-32. |
|38.||Thoma DS, Halg GA, Dard MM, Seibl R, Hammerle CH, Jung RE. Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipigs. Clin Oral Implants Res 2009;20:7-16. |
|39.||McGuire MK, Scheyer ET. Xenogeneic collagen matrix with coronally advanced flap compared to connective tissue with coronally advanced flap for the treatment of dehiscence-type recession defects. J Periodontol 2010;81:1108-17. |
|40.||Kakudo N, Minakata T, Mitsui T, Kushida S, Notodihardjo FZ, Kusumoto K. Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts. Plast Reconstr Surg 2008;122:1352-60. |
|41.||Hollinger JO, Hart CE, Hirsch SN, Lynch S, Friedlaender GE. Recombinant human platelet-derived growth factor: Biology and clinical applications. J Bone Joint Surg Am 2008;90:48-54. |
|42.||Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem 1991;45:319-26. |
|43.||Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638-46. |
|44.||Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral Maxillofac Surg 2004;62:489-96. |
|45.||Kaigler D, Avila G, Wisner-Lynch L, Nevins ML, Nevins M, Rasperini G, et al. Platelet-derived growth factor applications in periodontal and peri-implant bone regeneration. Expert Opin Biol Ther 2011;11:375-85. |
|46.||Schwarz F, Sager M, Ferrari D, Mihatovic I, Becker J. Influence of recombinant human platelet-derived growth factor on lateral ridge augmentation using biphasic calcium phosphate and guided bone regeneration: A histomorphometric study in dogs. J Periodontol 2009;80:1315-23. |
|47.||Nevins ML, Reynolds MA. Tissue engineering with recombinant human platelet-derived growth factor BB for implant site development. Compend Contin Educ Dent 2011;32:18, 20-7. |
|48.||Lynch SE, Wisner-Lynch L, Nevins M, Nevins ML. A new era in periodontal and periimplant regeneration: Use of growth-factor enhanced matrices incorporating rhPDGF. Compend Contin Educ Dent 2006;27:672-8. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15]