[Downloaded free from http://www.dentalhypotheses.com on Sunday, May 24, 2015, IP: 213.147.158.15] ORIGINAL HYPOTHESIS A new view on bone graft in dental implantation: Autogenous bone mixed with titanium granules Yeke Wu, Yunqiang Yang1, Yuqiao Zhou2, Yifei Gu3, Xuewei Fu3 Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, 1Center of Stomatology, Huazhong University of Science and Technology, Wuhan, 2Department of Oral Medicine, 3State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China A B S T R A C T Introduction: Dental implants have been widely applied in clinic for many years. However, the success rate is still challenging mainly because of bone deficiency. An ideal bone graft is traditionally thought to guide and induce new bone regeneration as well as been absorbed completely by human body. The Hypothesis: Autogenous bone mixed with titanium granules might be an ideal bone graft for dental implantation. Evaluation of the Hypothesis: First, we analyzed advantages of grafts of autogenous bone mixed with titanium granules, such as serving as a stable scaffold for wound healing and tissue regeneration, creating suitable microenvironment for implant–bone integration, shortening the new bone’s creeping distance, etc. Then we creatively hypothesized a novel alternative bone graft with premixed autogenous bone and non-absorbent titanium granules. Apart from repairing bone deficiency, our hypothesis could promote the integration between new bone and titanium implant from the perspective of microenvironment. We believe that the method is promising and worth extension in clinical application. Key words words: Autogenous bone graft, bone deficiency, dental implant, titanium granule Introduction Dental implants have been a feasible technique in the oral rehabilitation of edentulous and partially dentate patients with good long-term predictability for many years. [1] However, with the increasing frequency of implant placement, it is inevitable that the number of complications will also rise.[2] Among them bone deficiency ranks as one of the most often encountered problem. Numerous modalities of bone graft are proposed for the management of patients’ bone insufficiency. Currently, the main methods of Access this article online Quick Response Code: Website: www.dentalhypotheses.com DOI: 10.4103/2155-8213.110187 bone graft used clinically are as follows: (i) autogenous bone graft, which are derived from ilium, mandibular angle, chin, etc; (ii) artificial bone graft, such as bio-oss, hydroxyapatite, tricalcium phosphate, etc, mainly based on the guided bone regeneration (GBR) theory; and (iii) autogenous bone mixed with artificial bone.[3-5] These methods have their own merits as well as limitations. Autogenous bone is still the gold standard for defects filling caused by pathologies and traumas, and mainly for alveolar ridge reconstruction, allowing the titanium implants installation. It is characterized by osteogenic, osteoinductive and osteoconductive properties, as well as the lack of possible immunological reactions.[6,7] Nevertheless, it also has disadvantages as its limitation of drawing materials and easy to be absorbed.[8,9] For artificial bone graft bio-oss, the absorption process is fairly slow. Worse still, patients have to pay extra fee and suffer from the large bone defects. Titanium, a special metal with excellent biocompatibility and low resorbability, has long been used in implant Corresponding Author: Dr. Yang Yunqiang, No. 1095, Libera on Road, Wuhan, Hubei 430030, China. E-mail: [email protected] Jan-Mar 2013 / Vol 4 | Issue 1 Dental Hypotheses 13 [Downloaded free from http://www.dentalhypotheses.com on Sunday, May 24, 2015, IP: 213.147.158.15] Wu, et al.: Autogenous bone graft with titanium granules for dental implantation dentistry. Dental implant composed of titanium can perform mastication/chewing function for a long time after implantation. The first application of the irregularly shaped and porous titanium granules (PTG), TigranTM PTG in 1995 showed favorable osteoconductive and thrombogenic effects. [10] They imitated bone properties, stimulated osteoblasts colonization and osseointegration, and kept their volume during the entire healing period which ensures mechanical stability. Thereafter, titanium granules have been widely used for sinus floor augmentation, peri-implantitisrelated bone regeneration, furcation defects repair, onlay augmentation of deformed alveolar process, cystic cavities reconstruction, filling of extraction sockets, etc.[11-13] Traditional viewpoint for bone graft is primarily that graft should guide and induce new bone regeneration as well as been absorbed completely by human body.[14] Nowadays, we mainly focus on the filling of bone deficiency, instead of new bone regeneration and osseointegration. Hence, we need to seek for novel approach to settle the problem of bone deficiency, and improve the success rate of dental implantation. The Hypothesis In the paper, we hypothesized a novel approach of bone graft with pre-mixed autogenous bone and titanium granules (with a potential size of 0.7-1 mm) for bone deficiency repair, thus to reduce absorption after implant placement and improve the success rate of dental implantation. Such titanium granules are currently commercially available as Tigran™ (http:// www.tigran.se/en/). Evaluation of the Hypothesis Advantages As described in GBR, autogenous bone is easy to be absorbed and could not stabilize blood clot and granulation tissue to guide and induce new bone regeneration.[15-17] This is the major drawback of autogenous bone graft. However, it contains lots of cytokines and bone precursor cells that are necessary for osteogenesis, consequently promotes bone regeneration.[4,6,7] On the other hand, titanium is a special metal with excellent biocompatibility and non-resorbable. Therefore, when autogenous bone is mixed with titanium granules, they can act as stable scaffold without being absorbed due to their close integration with bone. However, titanium granules 14 Dental Hypotheses should be processed beforehand to form a hydrophilic surface for blood adhering, thus stabilize blood clot and promote formation of granulation tissue. If possible, bone morphogenetic protein could also be added on titanium surface to promote the integration with bone. Furthermore, the granule maybe designed with foramen to enhance the integration with dental implant, using techniques of acid etching, sandblasting, coating, etc. Bone metabolism is a dynamic equilibrium of osteogenesis and bone desorption. A layer of titanium oxide was found to form spontaneously on metallic titanium surface for calcified bone matrix deposition, constituting the basis for good biocompatibility of dental implant. The bonetitanium integration would provide a biocompatible surface for cell/tissue adherence and regeneration, similar to normal healing process. In addition, the recommendation that placement of dental implant immediately after tooth extraction to minimize bone loss has also verified the aforementioned theory.[1,18] Moreover, titanium can rarely be absorbed, so the integration between dental implant and bone is relatively stable. Taken together, the titanium granules with autogenous bone containing lots of bone precursor cells and cytokines may act as various active centers for osteogenesis and induce local new bone regeneration. Thus, they function as a whole and prevent alveolar bone absorption and collapse, thereby increasing the success rate of dental implant. Burchardt introduced the term “creeping substitution” to describe the process of autogenous bone graft incorporation in 1983. [19] Nowadays, creeping substitution theory still predominates in the field of bone grafting, that is, new bone replaces implant materials.[4] When autogenous bone mixed with titanium granules is implanted, titanium granules per se occupy certain space and cannot be absorbed, thus they decrease creeping substitution space and shorten the creeping distance, all of which benefits bone grafting. During bone grafting, bone tissue competes with soft tissue for survival space.[20] The integration between titanium and bone tissue is greater than that between titanium and soft tissue. Therefore, after autogenous bone mixed with titanium granules is implanted, titanium granules have priority to integrate with bone tissue. Thus, the implant height is maintained stable, like controlled tissue regeneration (CTR) technique,[21-23] and entry of soft tissue is prevented. Thereby, the success of dental implant is guaranteed. Jan-Mar 2013 / Vol 4 | Issue 1 [Downloaded free from http://www.dentalhypotheses.com on Sunday, May 24, 2015, IP: 213.147.158.15] Wu, et al.: Autogenous bone graft with titanium granules for dental implantation The bone-implant integration is a complex process, in which microenvironment around bone tissue definitely altered. However, the mechanisms involved are poorly understood. After implant placement, there is no obvious distinction between oxide layer surface and bone, even though the width of the interaction region of implant and peri-implant bone is greater than 1 mm. Hanawa had discovered a series of interesting alterations when observed implants with loading in clinic.[24] The formation of an inert titanium oxide layer, as thick as about 2000 m was found on the implant surface 6 years after implantation. Analysis of this newly formed layer revealed that it contains organics and inorganics (Ca, P, S), indicating that the oxide layer on implant surface is very sensitive to the intake and rise of these mineral ions and can respond to them, even though it is coated by a layer of protein. Moreover, exposure of the pure titanium or titanium alloy surface to the blood led to spontaneous formation of titanium phosphate and calcified compound containing hydroxyl groups on oxide layer surface, which suggested a reaction between titanium and water, mineral ions, and plasma had happened. Interestingly, it would accelerate calcium phosphate deposition on pure titanium surface in case of low PH at the implant area. Therefore, the oxide layer is a dynamic system. It plays the role of bone remodeling and forms a compatible interface between implant and bone. The interface may even spread to neighboring areas. Integration process of titanium granules and new bone induced a microenvironment in advance fitting for integration of titanium and bone. In the later implantation, the local environment will be more appropriate to osseointegration. So our hypothesis is highlighted in promoting osseointegration at microenvironment level, leading to increasing success rate of implantation. The characteristics of inorganic materials that undergo surface modifications on its own surface, or so-called physiologic camouflage to adapt to the need of body, are very rare in other inorganic materials. The application of titanium as graft material for bone graft not only involves bone mass but also induces osseointegration from the essence of bone and titanium integration, thus allowing the new generated bone more adapted to osseointegration. Disadvantages Although our hypothesis has so many aforementioned merits, it still has some shortcomings. First, the surface treatment of titanium granule is relatively a difficult technology, and determination of particle size is also Jan-Mar 2013 / Vol 4 | Issue 1 somewhat hard as we intend to find the most suitable particle sizes. Second, titanium granule plays an important role in our hypothesis, but the proportion of granules in mixture is difficult to quantify. As certain amount of bone mass is needed in implantation, we need to find out the most appropriate proportion. Third, the biggest innovation of this hypothesis is inducing proper microenvironment ahead of time, to make newly formed bone tissue adapt better to osseointegration. So our hypothesized method is not suitable for immediate implant, so one must implant bone graft first and then insert the implants. In clinical settings, we observed that the success rate of implantation is higher when using titanium mesh or membrane for bone graft. So, we deduce that our hypothesis is of great clinical significance and expect to be of great interest for both basic and clinical researchers. The characteristics of inorganic materials that undergo surface modifications on its own surface, or so-called physiologic camouflage to adapt to the need of body, are very rare in other inorganic materials. We carefully take the prominent features of titanium into consideration. Autogenous bone mixed with titanium granules can be expected to apply as a new method for bone graft in dental implantation. The idea could promote the integration of bone and implant from the perspective of microenvironment in addition to restore bone deficiency. If applicable, it will bring new ideas and views to the dental implants and bone graft. Furthermore, we could try to use titanium as a carrier to restore a variety of bone deficiency clinically. The titanium just acts as the reinforcing steel in the steel and concrete and it has broad prospects for application in the bone repair of cleft palate, jaw cyst, etc. However, there is no existence on any research on autogenous bone mixed with titanium granules applied to bone graft and it is just a hypothesis as stated above. Moreover, the volume of titanium granule and the proportion between titanium granule and autogenous bone are needed to be discussed. To some extent evidences from recent studies have supported our hypotheses. Further well-designed, double-blinded, randomized and controlled animal experiments and/or clinical trials with larger sample size in this field are essential to perfect our hypothesis. Dental Hypotheses 15 [Downloaded free from http://www.dentalhypotheses.com on Sunday, May 24, 2015, IP: 213.147.158.15] Wu, et al.: Autogenous bone graft with titanium granules for dental implantation References 1. Lang NP, Brägger U, Hämmerle CH, Sutter F. 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