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Current Pharmaceutical Biotechnology, 2017, 18, 19-32

REVIEW ARTICLE ISSN: 1389-2010 eISSN: 1873-4316

Molecular, Cellular and Pharmaceutical Aspects of Bone Grafting Materials and Membranes During Maxillary Sinus-lift Procedures. Part 1: A General Overview

Volume 17, Number 14

Current Pharmaceutical Biotechnology Impact Factor: 1.802

The international journal for timely in-depth reviews in Pharmaceutical Biotechnology

BENTHAM SCIENCE

Giovanna Iezzi1, Adriano Piattelli1,*, Alessandra Giuliani2, Carlo Mangano3, Licia Manzon4, Marco Degidi5, Flavia Iaculli1, Antonio Scarano6, Antonella Filippone7 and Vittoria Perrotti1 1

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Department of Medical, Oral and Biotechnological Sciences, Dental School, University G. D’Annunzio of ChietiPescara, Chieti, Italy; 2Department of Odontostomatologic and Specialized Clinical Sciences – Section of Biochemistry, Biology and Physics, Polytechnic University of Marche, Ancona, Italy; 3Private Practice, Gravedona (CO), Italy; 4 Sapienza University of Rome, Rome, Italy; 5Private Practice, Bologna, Italy; 6Center for Research on Ageing and Translational Medicine, CeSI-MeT, University of Chieti-Pescara, Chieti, Italy; 7Department of Neurosciences and Imaging, Section of Radiological Sciences, University G. D’Annunzio of Chieti-Pescara, Chieti, Italy

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DOI: 10.2174/13892010176661612211552 37

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Received: February 06, 2016 Revised: March 26, 2016 Accepted: November 25, 2016

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ARTICLE HISTORY

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Abstract: Sinus augmentation procedure has been demonstrated to be a highly predictable treatment in posterior maxilla atrophy. All the surgical interventions in the maxillary region require deep knowledge of anatomy and possible anatomical variations. In this article, pre-operative and post- operative assessments of sinus cavity as well as novel approaches to deepen our knowledge of the behavior of bone substitute materials are described. The awareness of the patient’s morphologic conditions enables exact planning of invasive surgery and aids to avoid complications. Pre- operative radiologic evaluation of the region before sinus lift is advisable both for a planning of the sinus augmentation and for selection and alignment of the optimum placement of implants. On the orthopantomography it is possible to measure the vertical dimension of graft, but not the volume and 3D changes. Cone-beam computed tomography (CBCT) has become the “gold standard” to plan a comprehensive implant treatment and to achieve a post-operative assessment. A computer-aided design/computer-aided manufacturing (CAD/CAM) technique is proposed to produce custom-made block grafts for sinus lift procedure, and a customized cutting guide to accurately place the lateral wall and ease membrane elevation. This procedure allows to reduce intervention time, to precisely adapt the scaffold, to reduce risk of complications and to improve operation quality. Recently, a novel approach has been used to deepen our knowledge of the behavior of BSBs: by means of synchrotron micro-tomography (SCT). It is a 3-D analyzing method, suitable to examine the dynamic and spatial arrangement of regenerative phenomena in complex anatomical structures such as bone, where tissues with several morphologies (alveolar process, unmineralized extracellular matrix, regenerated vessels, etc.) compete to achieve the final goal of bone regeneration.

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Keywords: Bone, grafting materials, radiography, sinus cavity.

Crestal bone resorption and pneumatization of the maxillary sinus are often observable after loss of upper posterior teeth. The edentulous posterior maxilla in these cases, usually shows an insufficient bone quantity for the replacement of missing teeth with dental implants. One of the common methods to achieve adequate bone volume tissue to allow a successful implant placement is sinus lift [1]. Clinical success has been obtained by grafting the maxillary sinus with

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*Address correspondence to this author at the Department of Medical, Oral and Biotechnological Sciences, Dental School, University G. D’Annunzio of Chieti-Pescara, Via dei vestini 31, 66100 Chieti, Italy; Tel: 0039 08713554083; Fax: 00 08713554076; E-mail: [email protected] 1873-4316/17 $58.00+.00

different bone substitute materials prior or simultaneously with implant placement [2]. All the surgical interventions in the maxillary region need deep knowledge of anatomy and possible anatomical variations in order to avoid pitfalls as well as an accurate preoperative diagnosis. 1.1. Sinus Cavity: Anatomical and Radiographical Insights The maxillary sinus is a wide pyramidal cavity with thin walls. In partially edentulous patients, teeth loss produces remodeling and resorption of the adjacent alveolar bone, often lead to the atrophy of the ridge. Atrophy-related resorption of the alveolar process results in a vertical bone loss, while progressive sinus pneumatization brings to an © 2017 Bentham Science Publishers

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Sinus augmentation procedure has been demonstrated to be a highly predictable treatment in posterior maxilla atrophy [6-19]. The sinus cavity is an important model of osteogenic chamber for new bone formation [20].

The radiation dose from CBCT is generally lower than in MDCT, but generally higher than in conventional dental radiography. The dose is dependent on the equipment type and exposure settings, especially the FOV, exposure time (s), tube current (mA) and the energy/potential (kV) [36]. Therefore, the personnel using a CBCT device must have appropriate knowledge of and training in patient radiation dose related to the specific device they are using, the specific patient they are studying and the specific examination they performing [36]. This emphasizes the importance of optimizing and standardizing imaging parameters in CBCT. Beyond a lower radiation dose, lower costs and easier availability, CBCT shows a higher contrast resolution when comparing with MDCT. As a matter of fact, CBCT has excellent highcontrast resolution as a result of small size (> than 0.076 mm) and geometry of voxel [36, 42]. However, CBCT has two major disadvantages with respect to MDCT. The first is the poor soft tissue resolution: it means that CBCT can be used for sinus imaging when soft tissue contrast resolution is not mandatory. If soft tissue evaluation is needed MDCT or magnetic resonance imaging (MRI) is indicated [36]. The second is a fair accurate conversion of density values in Hounsfield units (HU) [36]. It has been demonstrated that large errors can be seen when using the grey values in a quantitative way [36, 44]. This implies that, although it could be possible to obtain pseudo-Hounsfield units from certain CBCT, alternative methods of assessing bone tissue should be further investigated [44]. According to the previous considerations, CBCT has become the “gold standard” to plan a comprehensive implant treatment and to achieve a postoperative assessment. Nevertheless, we have to keep in mind the patient’s history, clinical information and previous images have to be available before CBCT imaging. Moreover, conventional radiographies, such as including panoramic and intraoral radiographies are still the basic imaging methods and CBCT should be used in more demanding cases, such as sinus floor augmentation [36].

1.2. Diagnostic Tools

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Conventional imaging compresses 3-dimensional (3D) anatomy into a 2-dimensional (2D) image, greatly limiting diagnostic performance [31, 32]. As a matter of fact, it provides important characteristics of the tooth and its surrounding tissues in the mesio-distal (proximal) plan only, whereas similar features presenting in the bucco-lingual plane (i.e. the third dimension) may not be fully recognized [33]. Diagnostic information in the missing “third dimension” is of particular relevance in surgical planning [34, 35], where the thickness of the cortical plate and its relationship to key adjacent anatomical structures, such as the maxillary sinus, should be understood [36]. Panoramic radiographs allow an assessment of the vertical dimension of graft, but do not supply information concerning volume and 3D changes [37].

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The awareness of the patient’s morphologic conditions enables precise planning of invasive surgery and aids to avoid complications [21-26]. The presence of anatomical variations within the maxillary sinus, such as septa, seems to enhance the risk of sinus elevation procedure [3, 27-29]. Therefore, radiologic evaluation of the region prior a sinus augmentation procedure is advisable both to permit for planning of the elevation and for selection and alignment of the ideal placement of implant [30].

tightly collimated narrow cone-shaped X-ray beam, instead of a fan-shaped X-ray beam used in MDCT [42]. It implies that images data are recorded in a single gantry rotation (180°- 360°), where the X-ray source and 2D detectors move synchronously around the patient’s head [36]. The height and diameter of the field of view (FOV) vary from small to large field examination [36, 42, 43].

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excavation of the alveolar process from the cranial aspect [3]. Dental implants supply prosthetic anchorage, but to reach this goal, sufficient bone quality and quantity in the implantation site are needed. To overcome the problem correlated to the alveolar bone resorption of the maxillary edentulous region a sinus lift procedure can be applied [1, 4, 5].

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Maestre-Ferrin et al. [38] compared the results of panoramic radiographs and computed tomography (CT) scans to define the prevalence, location and size of sinus septa. The authors showed that panoramic radiographs led to an erroneous diagnosis in 46.8% of the cases and concluded that, whenever a maxillary sinus lift is planned, a thorough study of the affected sinus should be made using CT. Multidetector CT (MDCT) is a very usual imaging technique, which allows the capture of information through a spiral movement of the radiation source and the detectors around the region of interest [39]. As a result of spiral, volumetric acquisition, MDCT units have very short examination times and isotropic images can be reformatted in any plane [40]. On the other hand, MDCT imparts relatively high radiation dose to the patients [40]. A further development and improvement of CT equipment have inspired researchers and clinicians to use it as low-dose CT: this is the cone-beam CT (CBCT) [39]. CBCT was introduced in the last decade for maxillofacial imaging and firstly reported in the literature by Mozzo et al. [41]. Nowadays, CBCT imaging is a widely-used imaging method in dentomaxillofacial radiology, allowing accurate 3D imaging of hard tissue structures [36]. CBCT scanners use a

1.3. Preoperative Assessment When performing invasive technique in the maxilla, such as sinus lift and bone grafting, some complications have been described [21-26]. In these cases, an accurate diagnosis is needed prior to dental implant treatment planning. Dental panoramic radiographs allow a complete observation of the maxillary sinus as well as the evaluation of the relationship between the level of the sinus floor and alveolar bone [45]. Unfortunately, their 2D nature limit the 3D visualization of the anatomical structures. Moreover, soft tissue of the maxillary sinus cannot be adequately observed on panoramic radiographs [45]. CBCT can correctly visualize teeth and adjacent anatomical structures with hard tissue high resolution, in spite of the lower radiation dose levels than MDCT [45].

Molecular, Cellular and Pharmaceutical Aspects of Bone Grafting Materials

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central role in determining the success rate of maxillary sinus grafting. Park et al. [48] showed that the CT detection rate of the posterior superior alveolar artery was 52.9% and the distance from the inferior border of the artery to the alveolar ridge was 16.4 ± 3.5 mm. The authors concluded that the probability of determining the artery with CT is 55%. Moreover, they suggested that if it is not identified, setting the upper border of the bony window in the premolar region, instead of the molar region, since the lower limit is suggested to improve the success rate of the maxillary sinus grafting by minimizing damage [48]. Other authors [49] suggested to limit the superior limit of the lateral window up to 18 mm from the ridge to elude any possible vascular damage.

Orhan et al. [46] showed that using CBCT the prevalence of maxillary sinus segments with septa was 58%. The location of septa assessed in their study showed a higher prevalence (69.1%) in the middle region than in the anterior and posterior ones [46]. The mean height of septa was 5.5 ± 2.64 mm. When comparing CBCT and panoramic radiographs, the detection rate of internally located septa, pneumatization and anteriorly located space occupying lesions was significantly reduced on panoramic radiographs. Moreover, a significant association was observed between the change in the detection rate on panoramic radiographs and septa height [45]. With decreasing height of septa, the detection rate on panoramic radiographs was gradually reduced. The threshold for clear observation of the septa by height was about 5 mm [45]. Similarly, a significant association was demonstrated between the change in the detection rate on panoramic radiography and the length of the major axis of space occupying lesions (including maxillary sinusitis, retention cysts, radicular cysts). Particularly, if the height of the major axis of space occupying lesions was < 4 mm, the detection rate on panoramic radiographs was significantly lower [45]. A significant association was observed between the change in the detection rate on panoramic radiographs and the width of mucosal thickening in the maxillary sinus. If the width of mucosal thickening was < 3 mm, the detection rate on panoramic radiographs was significantly reduced, whereas with increased width over 10 mm the detection rate on panoramic radiographs increased gradually [45]. It has been suggested that the threshold value to define a pathological sinus membrane was 2 mm or above [47].

Although the incidence of malignant incidental lesions is relatively low [45] the lack of soft tissue contrast for CBCT should be underlined. It means that in doubtful cases, MDCT or better MRI should be used.

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It is of crucial importance to pay attention to imaging of the maxillary sinus. In fact, symptoms commonly do not appear at the early stages of some lesions in the maxillary sinus. Therefore, the diagnosis is usually made casually when images of the area are obtained for other purposes [45]. Shiki et al. [40] showed that subjects expecting to undergo implant-supported rehabilitations of the maxilla had a two times greater prevalence of maxillary sinusitis than subjects with a chief compliant other than implant planning [45]. However, non-significant differences were found in area occupying lesions, discontinuity of the sinus floor, fluid retention, bone thickening, antroliths, sinus opacification and foreign bodies between the two groups [45].

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2. BIOMATERIALS

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Another application of preoperative assessment is the evaluation of the mean height of the usable bone in edentulous maxilla. Residual ridge resorption following tooth extraction is unavoidable process in posterior maxilla area [50]. Nimigean et al. [51] classified the average height of the available bone in the edentulous maxilla into three classes. Class 1 had a residual bone height of 10 mm, usually found in edentulism of no more than 5-years standing. Class 2 had a residual bone height of 5-10 mm, usually found in edentulism of 5-10 mm. Class 3 indicated a bone height of 0-5 mm, usually found in edentulism of more than 10 years [50]. Sinus augmentation is recommended to be performed in class 2 and 3. Another application in preoperative phase may be the CBCT volume analysis of the maxillary sinus to define the volume of graft material to use (Figs. 1-5).

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It is useful to remind that above the maxillary sinus septa and maxillary sinus disease, artery within the side wall of the maxillary sinus is a further anatomical border that can represent a problem during sinus lift procedure. As a matter of fact, an injury in the maxillary sinus and maxillary sinus septa can result in failure of the grafted material in case of perforation of the sinus membrane during the surgery [48]. On the contrary, the artery running along the side wall of the maxillary sinus is intraosseous artery anastomosing with the infraorbital artery and the posterior superior alveolar artery [48]. This can be impaired in performing the bony window for bone substitute material. Its damage, although not lifethreatening being a small vessel, can interfere with the elevation of the maxillary sinus membrane and fixation of the grafting material by reducing the visual field of surgery with blood [48]. Therefore, the artery course and position play a

Bone substitute materials (BSB) are available in unlimited amounts, in different shapes and size, but they require longer healing periods in comparison to autologous bone due to the reduced biological potential as they are cell-free. Tissue engineering procedures have allowed to successfully use osteoconductive scaffolds as carriers for mesenchymal stem cell and growth factors to promote tissue regeneration, accelerate bone formation and osseointegration of dental implants [52]. At present, allografts and xenografts materials are considered a valid alternative [53] though compared to autologous bone, they show smaller area of regenerated bone [54], lower defect regeneration, slower remodeling, slower or absent osteoclastic activity [55] and higher failure rate. Several different BSBs or combinations thereof have been used in sinus floor augmentation procedures, and the amount of vital bone seems to be an accurate indicator to evaluating the healing potential of the various materials [53, 56-65]. The issue of which is the best filling material for the sinus cavity has, then, relevant importance in clinical practice [20]. BSBs play a key role in dental practice due to their use in several fields of oral surgery and implant dentistry, e.g. to fill bone defects after tooth extraction, cysts or bone tumors removal, to treat peri-implant defects and in sinus floor augmentation procedures.

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Fig. (1). No nasal turbinate hypertrophy neither alterations or anatomical variants of the osteomeatal complex can be observed.

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Fig. (2). CBCT image showing right sinus membrane thickening can be observed as well as a scarce quantity of alveolar bone tissue.

Fig. (3). CBCT image showing moderate thickening of the sinus membrane and poor residual crestal bone.

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Molecular, Cellular and Pharmaceutical Aspects of Bone Grafting Materials

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Fig. (4). CBCT image showing: it is possible to observe a reduced bone thickness in the anterior area as well as and alveolar crest of 2-3 mm in height.

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Fig. (5). CBCT image showing antral artery is not evident in the paraxial sections.

A BSB used in bone regeneration procedures should: 1) Act as a scaffold to guide the bone formation;

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2) Possess pore volume, pore interconnectivity and pores size adequate to allow invasion of blood vessels; 3) Present mechanical characteristics similar to the tissues that have to be regenerated [14, 17, 57, 60]. BSBs should be histologically evaluated to analyze the bone healing processes [61]. Ideally, BSB should have biologic stability, provide volume maintenance, induce the formation of bone and allow for bone remodeling [61]. Extremely important is the macro- and microporosity of the BSB, and the interconnecting pore structure, which plays a crucial role in the bone tissue osteoconduction and vascularization of the grafted materials, supporting in such a way the proliferation and differentiation of osteoblasts and the ingrowth of newly formed bone into the grafted material particles [66]. In order to guarantee the success of the grafted materials a close contact between the BSB and the vascular-

ized host bone is necessary. This fact allows an adequate blood supply (angiogenesis), followed by osteogenesis [67]. An ideal BSB, besides other characteristics, should be able to be completely resorbed and replaced by newly formed bone. The capability to produce new bone must be correlated with the resorption rate of the BSB. The correlation between the timing for the resorption and replacement of BSB by vital bone is not yet fully understood [68]. 3. CUSTOM MADE POROUS SCAFFOLDS FOR BONE REGENERATION Surgery of the maxillary sinus is strictly related to the variable anatomical aspect of its inner part, that should be tridimensionally identified [21-26]. Despite the diagnostic progress, currently, sinus augmentation techniques still need bone substitute materials to be manually cut, shaped and formed at the time of grafting, resulting in an expensive and time-consuming process [69]. Furthermore, placing the lateral wall during lateral sinus elevation is still an intuitive

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This procedure allows to reduce intervention time, to precisely adapt the scaffold, to reduce risk of complications and to improve operation quality. However, the dimensions of the custom-made block are linked to the size of the outlined lateral bony window, complicating the filling of the space between the old and the new floor with the CAD/CAM block alone with the risk of small defects during the grafting. This limit, nevertheless, could be simply overcome by using particulate grafts in association with the custom-made, CAD/CAM block.

3.1. Manufacture of the Custom-Made Scaffold and the Cutting Guide

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As previously reported [69], the 3D geometry of the anatomically-shaped, custom-made scaffold is imported into a proprietary CAM software, used to create a set of tool-paths for fabrication on a proprietary computer- numerical-control (CNC) milling machine. A biomaterial block is then placed in the CNC milling machine and milled into the precise shape of the 3D project. In this way, an anatomically-shaped, custom-made scaffold is obtained. Finally, the same CAD/ CAM procedure can be used to fabricate a surgical polytetrafluoroethylene (PTFE) device, composed of a customized cutting guide, based on preoperative simulations [69]. Thanks to recent enhancement in CAD technology, linked to advanced 3D cutting machinery, it is now possible to cut a block of bone graft into the most proper shape, that has been preoperatively calculated using 3D simulation [69, 71]. Recently, an investigation has been conducted using a block of porous HA, possessing very good osteoconductivity and mechanical features appropriate for machine-cutting; it

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This technique is required in a larger cohort of subjects to validate the outcomes; anyway, computer-controlled fabrication via CAD/CAM technology can represent the ideal alternative in automating scaffold development, providing for variations in the shapes and requirements of different tissues and also size changes between different individuals [72]. In the near future, the accessibility of custom-made scaffolds engineered from the patient's own stem cells could revolutionize the way to treat bone defects in implantology [69] (Figs. 6-10).

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According to Mangano et al. [69], CAD/CAM procedure involves three stages: the virtual planning and design of the custom-made scaffold and the customized cutting guide; the manufacture of the scaffold and the guide; and the sinus elevation procedure. CBCT datasets of the posterior edentulous maxilla are acquired and consequently uploaded in the digital imaging and communications in medicine (DICOM) format into a specific 3D reconstruction software (MimicsR, Materialize, Leuven, Belgium) [69]. The hard tissue threshold is selected so that only bone is reconstructed from the slices. The software is able to carry out an accurate 3D reconstruction of the maxilla and the sinus; subsequently, an anatomically-shaped, custom-made scaffold for maxillary sinus augmentation is drawn [69]. The 3D geometries of the maxilla and the scaffold are then saved as stereolithographic (STL) files. Subsequently, these files are transferred to a 3D CAD program (RhinocerosR, Robert McNeel & Associates, Seattle, WA, USA). This software is used to pre-surgically outline the optimal lateral borders of the maxillary sinus for bone grafting surgery [69]. The maxillary sinus is outlined in 3D, and the software is used to trace the desired lateral window and osteotomy cuts in 3D. The cutting paths are verified in all planes of space to ensure that the planned osteotomy cuts would maximize the operator's ability to begin Schneiderian membrane reflection, therefore obtaining the optimal customized cutting guide [69]. This cutting guide is designed such that it would precisely fit onto the bone surface and would have a slit conforming to the simulated osteotomy plane. The 3D geometry of the cutting guide is then saved as a separate STL file [69].

was preoperatively cut into a highly accurate 3D shape, based on the preoperative simulation using CAD/CAM technologies [69]. Additionally, a customized CAD/CAM osteotomy template was designed and manufactured before surgery, based on preoperative simulations. Five patients underwent bilateral sinus floor augmentation; the guide was fitted onto the bone, and an osteotomy was performed through the slit. The bone window was outlined and the bony window fragment was moved medially, the sinus membrane was reflected and elevated and the space created; then, the anatomically-shaped custom-made HA block was inserted into the sinus, and its position was assessed by postoperative radiograph, showing the exact filling of the empty defect [69]. Six months after surgery, implants were positioned. Two years later, all implants were in function with the absence of clinical or prosthetic complications.

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process, strictly linked to the surgeon ability [70]. Nevertheless, during sinus lift procedure, inaccurate osteotomy cuts defining the lateral window may cause sinus membrane perforation, especially when the membrane is thin and the anatomical environment is demanding [63]. Recently, a computer-aided design/computer-aided manufacturing (CAD/CAM) technique to generate custom-made block grafts for sinus lift, and a customized cutting guide to accurately place the lateral wall and ease membrane elevation has been developed.

4. ANGIOGENESIS Angiogenesis is a process that determines the sprouting of new blood vessels from pre-existing vessels. The degree and speed of vascularization are the key determinants in the bone graft survival. The healing processes of the injured site need the presence of a higher oxygen content, of nutrients, and the removal of the cellular debris. To evaluate the presence of blood vessels in a tissue, it is necessary to count the microvessels (Microvessel Density -MVD) [73]. MVD seems to be correlated with the expression of the Vascular Endothelial Growth Factor (VEGF). This correlation has been supported by the studies on tumors conducted in our laboratory [74]. VEGF seems to be the major mechanism that influences angiogenesis and consequently osteogenesis during bone repair [67] promoting neovascularization, bone turnover, osteoblast migration [75]. VEGF is stimulated by Bone Morphogenetic Protein (BMP) and seems to regulate the angiogenesis at each stage of bone formation [76]. MVD has already been used to evaluate the presence of blood vessels and the angiogenetic properties of BSBs [77, 78]. Some studies showed a higher value of MVD and a higher percentage of newly formed bone in sites augmented using BSB than in nonaugmented sites [79].

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Fig. (6). CBCT data of edentulous maxilla of patient.

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Fig. (7). The virtual planning of customized cutting guide.

Fig. (8). The anatomically-shaped custom-made hydroxyapatite block grafted into the sinus.

5. RESORPTION PATTERN The ideal biomaterial should reabsorb slowly after placement and should integrate in the surrounding bone. His degradation rates should correspond to the rate of tissue regeneration to guarantee the original volume and strength of the biomaterial in the time and should be, finally, totally replaced by new bone [80]. It is of great interest the long-term outcome of grafting material. It is important to understand whether grafted particles can interfere with the regeneration process and with the long-term prognosis of dental implants that are inserted into this bone-graft composite. In literature, there is no unanimous view about long term anorganic bovine bone resorb ability and about his performance over long time. Several authors argue that anorganic bovine bone (ABB) is resorbable over time as they have observed the

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The long-lasting persistence of bovine grafting particles might also be explained by a bonding mechanism able to maintain the biomechanical integrity of bone/biomaterial during remodeling/ repair process [77]. Other authors have stated that ABB is non-resorbable [58, 90, 91] neither after 11 years [92]. These authors did not find any macrophages and mast cell on the granules or resorption lacunae on bonesubstitute surface [90, 92]. Mordenfeld et al. [92] claimed that the reported variations of graft particles over time may depend on many factors, such as the surgery including pressure at position of the grafting material, the initial percentage of particles in the graft, the particles size, the bone type (cortical or cancellous), the use of blood or saline, the biopsy technique, the histological preparation technique or the different biological response in animal studies. However, doubtless, it is preferable for dental implant integration and for implant prognosis to place implants in native natural bone and it has been demonstrated that bovine HA particles in contact with the titanium surface should reduce mechanical support for dental implants [93]. Anyway, irrespective of ABB particles resorb ability, histological reports [86, 94] on human implants retrieved from sinuses grafted with ABB have shown no contact between the biomaterial particles and the dental implant surface that was always surrounded and covered by newly-formed bone, achieving a very high BIC percentage. No epithelial cells or connective tissue resulted at the interface, no inflammatory cells were observed adjacent to the particles or at the bone-implant interface, no gaps were present at interface. Newly formed bone was constantly in tight contact with the bone substitutes particles. Consequently, ABB degradation does not seem to be crucial to achieve osseointegration and even if ABB particles are not completely resorbed and replaced by newly formed bone, there will be no adverse effects on the osseointegration of implants [86, 94]. The lack or the slow resorption could be an advantage to maintain the initial volume of the grafted area over time, while autogenous bone graft has shown, in some cases, after 8 months of healing, a resorption of more than 50% of the original volume [11].

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Fig. (9). The CBCT after 6 months.

Fig. (10). Rx after insertion of implants.

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presence on the particle surface of osteoclasts, resorption lacunae or the progressive increase of newly formed bone with the decrease over time of the residual particles in the specimen in vivo [14, 81-83]. Other authors describe only the signs of resorption or a decreased density of the graft over time [84]. Doubtless it is a very low resorption rate over a long period of time [53, 82, 85, 86]. Perrotti et al. [87] reported that osteoclasts are generated on, attached to, and resorb bovine bone (Bio-Oss) in vitro, although more slowly than native bone. The osteoclasts activity depends on the microenvironment of osteoclast-substratum interface. To resorb a substrate, osteoclasts’ membrane has to be sealed to it by cell receptors and protein of the integrin family, in such a way the acid secreted by osteoclasts determines mineral release from the substratum surface [58]. High calcium ions concentration on surface particles produces an increase in the cellular calcium levels that results in osteoclasts inhibition, detachment of the osteoclasts from the bone surface and consequently bone resorption inhibition also after many years [82, 88]. Elemental analysis has shown a relatively high calcium content of the ABB particles compared to natural bone which might have influence in the resorption process [89].

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Changes of augmented bone over time should be exactly measured to guarantee the predictability of sinus floor elevation, since loss of height and width may interfere with the following placement of dental implants. Concerning bone substitute materials, it has been demonstrated that autologous bone is completely resorbed over time, mostly if the graft is retrieved from the iliac crest [95, 96]. Many bone substitutes have been proposed and used during the last 2 decades, aiming to decrease morbidity of the sinus lift procedure and avoiding the need for a second surgical site [97, 98].

CBCT offers a secure technique for 3D visualization of the variations in the volume of newly-formed bone after sinus floor elevation. Several computer-based software programs are currently available. Volumetric changes of grafted maxillary sinus have been previously estimated by CT scan, both on humans [99] and on animals [100], demonstrating the predictability of the tool regarding graft prognosis. Moreover, CT is also helpful to plan the implantation time, to decide the size of implants, to precisely measure the bone grafting volume [100], as well as to accurately evaluate the 3D change of the graft material during the healing period. Volumetric data obtained by CBCT demonstrated high accuracy of estimation with a relative error below 1% with respect to the same measurement carried out during surgery [101, 102]. The variation of the bone volume has been precisely appreciated thanks to spatial resolution of CBCT (voxel size: > 0.1 mm). Therefore, CBCT is a fast, simple,

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Panoramic radiographs allow to estimate the vertical dimension of graft, but do not supply data about volume and 3D changes [37].

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6. POSTOPERATIVE ASSESSMENT

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Fig. (11). Panorex CBCT. Maxillary sinus augmentation (left) performed with biomaterial. Neither inflammatory reaction or thickening of sinus mucosa can be observed.

Fig. (12). CBCT. Maxillary sinus augmentation (left) performed with biomaterial. The biomaterial is well circumscribed as no scattered particles scattered into the sinus can be detected.

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Recently, a novel approach has been used to deepen our knowledge to evaluate the behavior of BSBs: synchrotron micro-tomography (SCT) [104]. It is a 3-D analyzing method, dedicated to assess the dynamic and spatial arrangement of regenerative phenomena in complex anatomical structures such as bone, where tissues with several morphologies (alveolar process, unmineralized extracellular matrix involvement, regenerated vessels) compete to achieve the final goal of bone regeneration [105, 106]. Traditionally, absorption imaging with SCT is conducted with almost no distance between sample and detector. In this context, among the several techniques available, SRT is used increasingly to achieve quantitative information concerning the mineral content of different areas of bone. In fact, the polychromatic source and cone-shaped beam geometry complicate assessment of bone mineral density by CBCT. Because absorption is strictly related to the amount of mineral in bone, a suitable calibration is able to precisely relate the reconstructed gray levels in SRT images, obtained using a monochromatic Xray beam, to the local bone mineral density [107]. Homogeneous materials with a low attenuation coefficient (like such as collagen, unmineralized extracellular matrix, vessels, nerves, etc.) or heterogeneous materials with a narrow range of attenuation coefficients (like the case of heterologous bone scaffolds or for graded mineralized bone) produce insufficient contrast for absorption imaging. In this case, the imaging quality can be increased using phase contrast tomography (PCT) with a wider distance between sample and detector [107, 108]. Additionally, whereas PCT is based on a single distance between the detector and the sample, holotomography (HT) includes imaging at different distances, then

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relatively accurate, and promising approach to quantifying long-term changes in the grafted area [103]. Further efforts are needed in order to standardize and make reproducible 3D analyzing software program for CBCT quantitative evaluation such as volume analysis.

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Fig. (13). Sagittal and coronal sections after sinus augmentation. No nasal turbinate hypertrophy neither obstructions of the ostiomeatal complex can be observed. Panorex. sinus lift (left).

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Conventional histological evaluation and corresponding histomorphometric measurements may be helpful to better understand the behavior of BSB by providing a qualitative and quantitative of the bone healing. Specifically, evaluations on the influence of the BSBs on bone structure and on the activities of the cells involved in the regeneration/ remodeling process can be undertaken (Figs. 11-13).

Fig. (14). HT (rearranged by Fig. 5B of Ref. [100]). Sub-volume of a Human Mandible 3D reconstruction: all other phases were virtually removed except for bone (white) and vessels (red).

Molecular, Cellular and Pharmaceutical Aspects of Bone Grafting Materials

combining the phase shift information to generate 3D reconstructions. HT is helpful when the material of interest has very small changes in attenuation coefficients, which lead to unsatisfactory imaging outcomes even with phase contrast techniques [109] (Fig. 14).

Current Pharmaceutical Biotechnology, 2017, Vol. 18, No. 1 [8]

[9]

CONCLUSION

CONFLICT OF INTEREST

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[11]

Barone, A.; Santini, S.; Marcaccini, S.; Giacomelli, L.; Gherone, E.; Covani, U. Osteotomy and membrane elevation during the maxillary sinus augmentation procedure. A comparative study: piezoelectric device vs. conventional rotative instruments. Clin. Oral. Implants Res., 2008, 19(5), 511-515. Barone, A.; Orlando, B.; Tonelli, P.; Covani, U. Survival rate for implants placed in the posterior maxilla with and without sinus augmentation: A comparative cohort study. J. Periodontol., 2011, 82(2), 219-226. Hallman, M.; Lederlund, A.; Linsskog, S.; Lundgren, S.; Sennerby, L. A clinical histologic study of bovine hydroxyapatite in combination with autogenous bone and fibrin glue for maxillary sinus floor augmentation. Results after 8 months of healing. Clin. Oral. Implants Res., 2001, 12(2), 135-143. Hallman, M.; Sennerby, L.; Lundgren, S. A clinical and histologic evaluation of implant integration in the posterior maxilla after sinus floor augmentation with autogenous bone, bovine hydroxyapatite, or 20:80 mixture. Int. J. Oral. Maxillofac. Implants, 2002, 17(5), 635-643. Karabuda, C.; Ozdemir, O.; Tosun, T.; Anil, A.; Olgac, V. Histological and clinical evaluation of 3 different grafting materials for sinus lifting procedure based on 8 cases. J. Periodontol., 2001, 72(10), 1436-1442. Lee, Y.M.; Shin, S.Y.; Kim, J.Y.; Kye, S.B.; Ku, Y.; Rhyv, I.C. Bone reaction to bovine hydroxyapatite for maxillary sinus floor augmentation: Histologic results in humans. Int. J. Periodontics Restorative Dent., 2006, 26(5), 471-481. Piattelli, M.; Bavero, G.F.; Scarano, A.; Orsini, G.; Piattelli, A. Bone reactions to anorganic bovine bone (Bio-Oss) used in sinus lifting procedure: A histologic long-term report of 20 cases in man. Int. J. Oral. Maxillofac. Implants, 1999, 14(6), 835-840. Tadjoedin, E.S.; de Lange, G.L.; Bronckers, A.L.J.J.; Lyaruu, D.M.; Burger, E.H. Deproteinized cancellous bovine bone (BioOss®) as bone substitute for sinus floor elevation. A retrospective, histomorphometrical study of five cases. J. Clin. Periodontol., 2003, 30(3), 261-270. Valentini, P.; Abensur, D.; Wenz, B.; Peetz, M.; Schenk, R. Sinus grafting with porous bone mineral (Bio-Oss®) for implant placement: A 5-year study on 15 patients. Int. J. Periodontics Restorative Dent., 2000, 20(3), 245-253. Wallace, S.S.; Froum, S.J. Effect of maxillary sinus augmentation on the survival of endosseous dental implants. A systematic review. Ann. Periodontol., 2003, 8(1), 328-343. Yamanichi, N.; Itose, T.; Neiva, R.; Wang, H.L. Long-term evaluation of implant survival in augmented sinuses: A case series. Int. J. Periodontics Restorative Dent., 2008, 28(2), 163-169. Yildirim, M.; Spiekermann, H.; Biesterfeld, S.; Edelhoff, D. Maxillary sinus augmentation using xenogenic bone substitute material Bio-Oss in combination with venous blood. A histologic and histomorphometric study in humans. Clin. Oral. Implants Res., 2000, 11(3), 217-229. Mazor, Z.; Horowitz, R.A.; Del Corso, M.; Prasad, H.S.; Rohrer, M.D.; Dohan Ehrenfest, D.M. Sinus floor augmentation with simultaneous implant placement using Choukroun’s platelet-rich fibrin as the sole grafting material: a radiologic and histologic study at 6 months. J. Periodontol., 2009, 80(12), 2056-2064. González-Santana, H.; Peñarrocha-Diago, M.; Guarinos-Carbó, J.; Sorní-Bröker, M. A study of the septa in the maxillary sinuses and the subantral alveolar processes in 30 patients. J. Oral Implantol., 2007, 33(6), 340-343. Kim, M.J.; Jung, U.W.; Kim, C.S.; Kim, K.D.; Choi S.H.; Kim, C.K. Maxillary sinus septa: prevalence, height, location and morphology. A reformatted computed tomography scan analysis. J. Periodontol., 2006, 5(5), 903-908. Koymen, R.; Gocmen-Mas, N.; Karacayli, U.; Ortakoglu, K.; Ozen, T.; Yazici, A.C. Anatomic evaluation of maxillary sinus septa. Surgery and Radiology. Clin. Anat., 2009, 22(5), 563-570. Krennmair, G.; Ulm, C.; Lugmayr, H.; Solar, P. The incidence, location, and height of maxillary sinus septa in the edentulous and dentate maxilla. J. Oral Maxillofac. Surg., 1999, 57(6), 667-771. Naitoh, M.; Suenaga, Y.; Kondo, S.; Gotoh, K.; Ariji, E. Assessment of maxillary sinus septa using cone-beam computed tomography: Etiological consideration. Clin. Implant Dent. Relat. Res., 2009, 11(S1), 52-58.

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The present article shows the importance of a deep knowledge of anatomy and possible anatomical variations of sinus cavity, thus the role of a proper radiological assessment of the region before sinus augmentation procedure to avoid complications and for a successful outcome of the sinus elevation procedure. Despite those advances, the choice of the best bone substitute materials still remains crucial. Therefore, an overview of all the biomaterials that can be used with success in maxillary sinus elevation will be conducted in Part 2 of the article.

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[14]

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This work was partially supported by the Ministry of Education, University, Research (M.I.U.R.), Rome, Italy and by the Program PRIN (Prot. 20102ZLNJ5), M.I.U.R., Rome, Italy.

[4]

[5]

[6]

[7]

rD

Fo

ot

[3]

Nishibori, M.; Betts, N.J.; Salama, H.; Listgarten, M.A. Short-term healing of autogenous and allogeneic bone grafts after sinus augmentation: A report of 2 cases. J. Periodontol., 1994, 65(10), 958966. Chackartchi, T.; Iezzi, G.; Goldstein, M.; Klinger, A.; Soskolne, A.; Piattelli, A.; Shapira, L. Sinus floor augmentation using large (1-2 mm) or small (0.25-1 mm) bovine bone mineral particles: a prospective, intra-individual controlled clinical, microcomputerized tomography and histomorphometric study. Clin. Oral. Implants Res., 2011, 22(5), 473-480. Krennmair, G.; Ulm, C.; Lugmayr, H. Maxillary sinus septa: Incidence, morphology and clinical implications. J. Craniomaxillofac. Surg., 1997, 25(5), 261-265. H¨urzeler, M.B.; Kirsch, A.; Ackermann, K.L.; Qui˜nones, C.R. Reconstruction of the severely resorbed maxilla with dental implants in the augmented maxillary sinus: A 5-year clinical investigation. Int. J. Oral. Maxillofac. Implants, 1996, 11(4), 466-475. Valentini, P.; Abensur, D. Maxillary sinus floor elevation for implant placement with demineralized freeze-dried bone and bovine bone (Bio-Oss): A clinical study of 20 patients. Int. J. Periodont. Restorative Dent., 1997, 17(3), 232-241. Artzi, Z.; Nemcovsky, C.E.; Dayan, D. Bovine-HA spongiosa blocks and immediate implant placement in sinus augmentation procedures. Histopathological and histomorphometric observations on different histological stainings in 10 consecutive patients. Clin. Oral. Implants Res., 2002, 13(4), 420-427. Barone, A.; Santini, S.; Sbordone, L.; Crespi, R.; Covani, U. A clinical study of the outcomes and complications associated with maxillary sinus augmentation. Int. J. Oral. Maxillofac. Implants, 2006, 21(1), 81-85.

N

[2]

[17]

[18]

REFERENCES [1]

[16]

tri

ACKNOWLEDGEMENTS

[15]

is

on al

U

se

Like most specialists in the implant and biomaterial field of research, the authors of this article are currently involved in experimental studies with various dental implants and biomaterial companies. However, this general literature review work focuses only on general established knowledge in the clinical and biological aspects of these materials and therefore coauthors do not have any conflict of interest to report for this work.

bu tio n

O

[13]

[19]

[20]

[21]

[22]

[23]

[24] [25]

29

30 Current Pharmaceutical Biotechnology, 2017, Vol. 18, No. 1

[37] [38]

[39]

[40]

[41]

[42] [43]

[44]

[45]

[46]

[47]

nl y

O

[53]

[54]

[55]

[56]

bu tio n

[36]

[52]

tri

[35]

[51]

phy for mucosal thickening. Eur. Arch. Otorhinolaryngol., 2009, 266(4), 519-525. Park, W.H.; Choi, S.Y.; Kim, C.S. Study on the position of posterior superior alveolar artery in relation to the performance of the maxillary sinus bome graft procedure in Korean population. J. Korean Assoc. Oral Maxillofac. Surg., 2012, 38(2), 71-77. Güncü, G.N.; Yildirim, Y.D.; Wang, H.L.; Tözüm, T.F. Location of posterior superior alveolar artery and evaluation of maxillary sinus anatomy with computerized tomography: A clinical study. Clin. Oral. Implants Res., 2011, 22(10), 1164-1167. Lee, J.E.; Jin, S.H; Ko, Y.; Park, J.B. Evaluation of anatomical considerations in the posterior maxillae for sinus augmentation. World J. Clin. Cases., 2014, 2(11), 683-688. Nimigean, V.; Nimigean, V.R.; Măru, N.; Sălăvăstru, D.I.; Bădiţă, D.; Tuculină, M.J. The maxillary sinus floor in the oral implantology. Rom. J. Morphol. Embryol., 2008, 49(4), 485-489. Pieri, F.; Lucarelli, E.; Corinaldesi, G.; Iezzi, G.; Piattelli, A.; Giardino, R.; Bassi, M.; Donati, D.; Marchetti, C. Mesenchymal stem cells and platelet-rich plasma enhance bone formation in sinus grafting: A histomorphometric study in minipigs. J. Clin. Periodontol., 2008, 35(6), 539-546. Scarano, A.; Degidi, M.; Iezzi, G.; Pecora, G.; Piattelli, M.; Orsini, G.; Caputi, S.; Perrotti, V.; Mangano, C.; Piattelli, A. Maxillary sinus augmentation with different biomaterials: a comparative histologic and histomorphometric study in man. Implant Dent., 2006, 15(2), 197-207. Neugebauer, J.; Iezzi, G.; Perrotti, V.; Fischer, J.H.; Khoury, F.; Piattelli, A.; Zoeller, J.E. Experimental immediate loading of dental implants in conjunction with grafting procedures. J. Biomed. Mater. Res. B Appl. Biomater., 2009, 91(2), 604-612. Schwarz, F.; Herten, M.; Ferrari, D.; Wieland, M.; Schmitz, L.; Engelhardt, E.; Becker, J. Guided bone regeneration at dehiscencetype defects using biphasic hydroxyapatite + beta tricalcium phosphate Bone Ceramic) or a collagen-coated natural bone mineral (BioOss Collagen): An immunohistochemical study in dogs. Int. J. Oral Maxillofac. Surg., 2007, 36(12), 1198-1206. Galindo-Moreno, P.; Avila, G.; Fernandez-Barbero, J.E.; Mesa, F.; O’Valle-Ravassa, F.; Wang, H.L. Clinical and histologic comparison of two different composite grafts for sinus augmentation: a pilot study. Clin. Oral. Implants Res., 2008, 19(8), 755-759. Galindo-Moreno, P.; Moreno-Riestra, I.; Avila, G.; Padial-Molina, M.; Paya, J.A.; Wang, H.L.; O’Valle, F. Effect of anorganic bovine bone to autogenous cortical bone ratio upon bone remodeling patterns following maxillary sinus augmentation. Clin. Oral. Implants Res., 2011, 22(8), 857-864. Ewers, R.; Goriwoda, W.; Schopper, C.; Moser, D.; Spassova, E. Histologic findings at augmented bone areas supplied with two different bone substitute materials combined with sinus floor lifting. Report of one case. Clin. Oral. Implants Res., 2004, 15(1), 96-100. Mangano, C.; Scarano, A.; Pernotti, V.; Iezzi, G.; Piattelli, A. Maxillary sinus augmentation with a porous synthetic hydroxyapatite and bovine derived hydroxyapatite: Comparative clinical and histological study. Int. J. Oral. Maxillofac. Implants., 2007, 22(6), 980-986. Froum, S.J.; Wallace, S.S.; Cho, S.C.; Elian, N.; Tarnow, D.P. Histomorphometric comparison of a biphasic bone ceramic to anorganic bovine bone for sinus augmentation: 6-to-8-month postsurgical assessment of vital bone formation. A pilot study. Int. J. Periodontics Restorative Dent., 2008, 28(3), 273-281. Kim, Y.K.; Yun, P.Y.; Kim. S.G.; Lim, S.C. Analysis of the healing process in sinus bone grafting using various grafting materials. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2009, 107(2), 204-211. Kuhl, S.; Gotz, H.; Hansen, T.; Kreisler, M.; Behneke, A.; Heil, U.; Duscher, H.; d’Hoedt, B. Three-dimensional analysis of bone formation after maxillary sinus augmentation by means of microcomputed tomography: a pilot study. Int. J. Oral. Maxillofac. Implants, 2010, 25(5), 930-938. Lindgren, C.; Sennerby, L.; Mordenfeld, A.; Hallman, M. Clinical histology of microimplants placed in two different biomaterials. Int. J. Oral. Maxillofac. Implants., 2009, 24(6), 1093-1100. Lambert, F.; Léonard, A.; Drion, P.; Source, S.; Layrolle, P.; Rompen, E. Influence of space-filling materials in subantral bone augmentation: Blood clot vs autogenous bone chips vs bovine hydroxyapatite. Clin. Oral. Implants Res., 2011, 22(5), 538-545.

[57]

is

[34]

[50]

se

[33]

[49]

rD

[32]

[48]

U

[31]

Fo

[30]

ot

[29]

on al

[28]

N

[27]

Velasquez-Plata, D.; Hovey, L.R.; Peach, C.C.; Alder M.E. Maxillary sinus septa: A 3-dimensional computerized tomographic scan analysis. Int. J. Oral. Maxillofac. Implants., 2002, 17(6), 854-860. Betts, N.J.; Miloro, M. Modification of the sinus lifts procedure for septa in the maxillary antrum. J. Oral Maxillofac. Surg., 1994, 52(3), 332-333. Chanavaz, M. Maxillary sinus: Anatomy, physiology, surgery, and bone grafting related to implantology - eleven years of surgical experience. J. Oral Implantol., 1990, 16(3), 199-209. Van den Bergh, J.P.; ten Bruggenkate, C.M.; Disch, F.J.; Tuinzing, D.B. Anatomical aspects of sinus floor elevations. Clin. Oral. Implants Res., 2000, 11(3), 256-265. Imhof, H.; Czerny, C.; Dirisamer, A. Head and neck imaging with MDCT. Eur. J. Radiol., 2003, 45(S1), 23-31. Webber, R.L.; Messura, J.K. An in vivo comparison of digital information obtained from tuned-aperture computed tomography and conventional dental radiographic imaging modalities. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 1999, 88(2), 239-247. Cohenca, N.; Simon, J.H.; Roges, R.; Morag, Y.; Malfaz, J.M. Clinical indications for digital imaging in dento-alveolar trauma. Part 1: traumatic injuries. Dent. Traumatol., 2007, 23(2), 95-104. Patel, S.; Dawood, A.; Whaites, E.; Pitt Ford, T. New dimensions in endodontic imaging: part 1. Conventional and alternative radiographic systems. Int. Endod. J., 2009, 42(6), 447-462. Velvart, P.; Hecker, H.; Tillinger, G. Detection of the apical lesion and the mandibular canal in conventional radiography and computed tomography. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2001, 92(6), 682-688. Low, M.T.L.; Dula, K.D.; Bu¨rgin, W.; von Arx, T. Comparison of periapical radiography and limited cone-beam tomography in posterior maxillary teeth referred for apical surgery. J. Endod., 2008, 34(4), 557-562. Suomalainen, A.; Pakbaznejad Esmaeili, E.; Robinson, S. Dentomaxillofacial imaging with panoramic views and cone beam CT. Insights Imaging., 2015, 6(1), 1-16. Juodzbalys, G.; Raustia, A.M. Accuracy of clinical and radiological classification of the jawbone anatomy for implantation - a survey of 374 patients. J. Oral Implantol., 2004, 30(1), 30-39. Maestre-Ferrín, L.; Carrillo-García, C.; Galán-Gil, S.; PeñarrochaDiago, M.; Peñarrocha-Diago, M. Prevalence, location, and size of maxillary sinus septa: Panoramic radiograph versus computed tomography scan. J. Oral Maxillofac. Surg., 2011, 69(2), 507-511. Guerrero, M.E.; Jacobs, R.; Loubele, M.; Schutyser, F.; Suetens, P.; van Steenberghe, D. State-of-the-art on cone beam CT imaging for preoperative planning of implant placement. Clin. Oral. Investig., 2006, 10(1), 1-7. Valentin, J.; International Commission on Radiation Protection. Managing patient dose in multi-detector computed tomography(MDCT). ICRP Publication 102. Ann. ICRP., 2007, 37(1), 1-79, iii. Mozzo, P.; Procacci, C.; Tacconi, A.; Martini, P.T.; Bergamo, I.A. A new volumetric CT machine for dental imaging based on the cone-beam technique: Preliminary results. Eur. Radiol., 1998, 8(9), 1558-1564. Scarfe, W.C.; Farman, A.G. What is cone-beam CT and how does it work? Dent. Clin. North Am., 2008, 52(4), 707-730. Nemtoi, A.; Czink, C.; Haba, D.; Gahleitner, A. Cone beam CT: A current overview of devices. Dentomaxillofac. Radiol., 2013, 42(8), 20120443. Pauwels, R.; Nackaerts, O.; Bellaiche, N.; Stamatakis, H.; Tsiklakis, K.; Walker, A.; Bosmans, H.; Bogaerts, R.; Jacobs, R.; Horner, K.; SEDENTEXCT Project Consortium. Variability of dental cone beam CT grey values estimations. Br. J. Radiol., 2013, 86(1021), 20120135. Shiki, K.; Tanaka, T.; Kito, S.; Wakasugi-Sato, N.; MatsumotoTakeda, S.; Oda, M.; Nishimura, S.; Morimoto, Y. The significance of cone beam computed tomography for the visualization of anatomical variations and lesions in the maxillary sinus for patients hoping to have dental implant-supported maxillary restorations in a private dental office in Japan. Head Face Med., 2014, 28, 10, 20. Orhan, K.; Kusakci Seker, B.; Aksoy, S.; Bayindir, H.; Berberoğlu, A.; Seker, E. Cone beam CT evaluation of maxillary sinus septa prevalence, height, location and morphology in children and an adult population. Med. Princ. Pract., 2013, 22(1), 47-53. Cagici, C.A.; Yilmazer, C.; Hurcan, C.; Ozer, C.; Ozer, F. Appropriate interslice gap for screening coronal paranasal sinus tomogra-

Pe rs

[26]

Iezzi et al.

[58]

[59]

[60]

[61]

[62]

[63]

[64]

Molecular, Cellular and Pharmaceutical Aspects of Bone Grafting Materials

[75]

[76]

[77]

[78]

[79]

[80] [81]

[82]

[83]

[87]

[88]

nl y

[89]

[91]

[92]

[93]

bu tio n

O

[90]

tri

[74]

[86]

[94]

[95]

[96]

[97]

[98]

[99]

[100]

[101]

[102]

[103]

31

Wallace, S.S.; Froum, S.J.; Tarnow, D.P. Histologic evaluation of a sinus elevation procedure: a clinical report. Int. J. Periodontics Restorative Dent., 1996, 16(1), 46-51. Sartori, S.; Silvestri, M.; Forni, F.; Icaro Cornaglia, A.; Tepei, P.; Cattaneo, V. Ten-year follow-up in a maxillary sinus augmentation using anorganic bovine bone (Bio-Oss). A case report with histomorphometric evaluation. Clin. Oral. Implants Res., 2003, 14(3), 369-372. Scarano, A.; Pecora, G.; Piattelli, M.; Piattelli, A. Osseointegration in a sinus augmented with bovine porous bone mineral: Histological results in an implant retrieved 4 years after insertion. A case report. J. Periodontol., 2004, 75(8), 1161-1166. Perrotti, V.; Nicholls, B.M.; Horton, M.A.; Piattelli, A. Human osteoclast formation and activity on a xenogenous bone mineral. J. Biomed. Mater. Res. A, 2009, 90(1), 238-246. Ramaswamy, Y.; Haynes, D.R.; Berger, G.; Gildenhaar, R.; Lucas, H.; Holding, C.; Zreiqat, H. Bioceramics composition modulate resorption of human osteoclasts. J. Mater. Sci. Mater. Med., 2005, 16(12), 1199-1205. Traini, T.; Degidi, M.; Sammons, R.; Stanley, P.; Piattelli, A. Histological and elemental microanalytical study of anorganic bovine bone substitution following sinus floor augmentation in humans J. Periodontol., 2008, 79(7), 1232-1240. Schlegel, A.K.; Donath, K. BIO-OSS-a resorbable bone substitute? J. Long Term Eff. Med. Implants., 1998, 8(3-4), 201-209. Rosenlicht, J.L.; Tarnow, D.P. Human histologic evidence of integration of functionally loaded hydroxyapatite-coated implants placed simultaneously with sinus augmentation: A case report 2 1/2 years postplacement. J. Oral Implantol., 1999, 25(1), 7-10. Mordenfeld, A.; Hallman, M.; Johansson, C.B.; Albrektsson, T. Histological and histomorphometrical analyses of biopsies harvested 11 years after maxillary sinus floor augmentation with deproteinized bovine and autogenous bone. Clin. Oral Implants Res., 2010, 21(9), 961-970. Haas, R.; Mailath, G.; Dörtbudak, O.; Watzek, G. Bovine hydroxyapatite for maxillary sinus augmentation: Analysis of interfacial bond strength of dental implants using pull-out tests. Clin. Oral. Implants Res., 1998, 9(2), 117-122. Valentini, P.; Abensur, D.; Densari, D.; Graziani, J.N.; Hammerle, C.H.F. Histological evaluations of Bio-Oss® in a 2- stage sinus floor elevation and implantation procedure. A human case report. Clin. Oral. Implants Res., 1998, 9(1), 59-64. Johansson, B., Grepe, A.; Wannfors, K.; Aberg, P. CT-scan in assessing volumes of bone grafts to the heavily resorbed maxilla. J. Craniomaxillofac. Surg., 1998, 26(S1), 85. Johansson, B., Grepe, A.; Wannfors, K.; Hirsch, J.M. A clinical study of changes in the volume of bone grafts in the atrophic maxilla. Dentomaxillofac. Radiol., 2001, 30(3), 157-161. Bouchlariotou, I.; Bernard, J.P.; Carrel, J.P.; Vazquez, L. Longterm stability of osseointegrated implants in bone regenerated with a collagen membrane in combination with a deproteinized bovine bone graft: 5-year follow-up of 20 implants. POSEIDO, 2013, 1(1), 45-53. Toeroek, R.; Mazor, Z.; Del Corso, M.; Dohan Ehrenfest, D.M. The concept of Screw-Guided Bone Regeneration (S-GBR). Part 1: From sinus-lift to general applications in the resorbed maxilla and mandible. POSEIDO, 2013, 1(2), 69-84. Sbordone, C.; Sbordone, L.; Toti, P.; Martuscelli, R.; Califano, L.; Guidetti, F. Volume changes of grafted autogenous bone in sinus augmentation procedure. J. Oral Maxillofac. Surg., 2011, 69(6), 1633-1641. Jensen, T.; Schou, S.; Svendsen, P.A.; Forman, J.L.; Gundersen, H.J.; Terheyden, H.; Holmstrup, P. Volumetric changes of the graft after maxillary sinus floor augmentation with Bio-Oss and autogenous bone in different ratios: A radiographic study in minipigs. Clin. Oral Implants Res., 2012, 23(8), 902-910. Bornstein, M.M.; Lauber, R.; Sendi, P.; von Arx, T. Comparison of periapical radiography and limited cone-beam computed tomography in mandibular molars for analysis of anatomical landmarks beforeapical surgery. J. Endod., 2011, 37(2), 151-157. Stratemann, S.A.; Huang, J.C.; Maki, K.; Miller, A.J.; Hatcher, D.C. Comparison of cone beam computed tomography imaging with physical measures. Dentomaxillofac. Radiol., 2008, 37(2), 8093. Ohe, J.Y.; Kim, G.T.; Lee, J.W.; Al Nawas, B.; Jung, J.; Kwon, Y.D. Volume stability of hydroxyapatite and β -tricalcium phos-

is

[73]

[85]

se

[72]

[84]

rD

[71]

U

[70]

Fo

[69]

ot

[68]

on al

[67]

N

[66]

Cordaro, L.; Bosshardt, D.D.; Palattella, P.; Rao, W.; Serino, G.; Chiapasco, M. Maxillary sinus grafting with Bio-Oss or Straumann® BoneCeramic: Histomorphometric results from a randomized controlled multicenter clinical trial. Clin. Oral. Implants Res., 2008, 19(8), 796-803. Campion, C.R.; Chander, C.; Buckland, T.; Hing, K. Increasing strut porosity in silicate-substituted calcium-phosphate bone graft substitutes enhance oseointegration. J. Biomed. Mater. Res. B Appl. Biomater., 2011, 97(2), 245-254. Carano, R.A.; Filvaroff, E.H. Angiogenesis and bone repair. Drug Discov. Today, 2003, 8(21), 980-989. Landi, L.; Pretel, R.W.; Hakimi, N.M.; Setayesh, R. Maxillary sinus floor elevation using a combination of DFDBA and bovinederived porous hydroxyapatite: A preliminary histologic and histomorphometric report. Int. J. Periodontics Restorative Dent., 2000, 20(6), 575-583. Mangano, F.; Zecca, P.; Pozzi-Taubert, S.; Macchi, A.; Ricci, M.; Luongo, G.; Mangano, C. Maxillary sinus augmentation using computer-aided design/computer-aided manufacturing (CAD/ CAM) technology. Int. J. Med. Robot., 2013, 9(3), 331-338. Mandelaris, G.A.; Rosenfeld, A.L. A novel approach to the antral sinus bone graft technique: the use of a prototype cutting guide for precise outlining of the lateral wall. A case report. Int. J. Periodont. Restorative Dent., 2008, 28(6), 569-575. Oka, K.; Murase, T.; Moritomo, H.; Goto, A.; Sugamoto, K.; Yoshikawa, H. Corrective osteotomy using customized hydroxyapatite implants prepared by preoperative computer simulation. Int. J. Med. Robot., 2010, 6(2), 186-193. Smith, M.H.; Flanagan, C.L.; Kemppainen, J.M.; Sack, J.A.; Chung, H.; Das, S.; Hollister, S.J.; Feinberg, S.E. Computed tomopgraphy based tissue-engineered scaffolds in craniomaxillofacial surgery. Int. J. Med. Robot., 2007, 3(3), 207-216. Duda, D.G.; Cohen, K.S.; Scadden, D.T.; Jain, R.K. A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood. Nat. Protoc., 2007, 2(4), 805-810. Artese, L.; Rubini, C.; Ferrero, G.; Fioroni, M.; Santinelli, A.; Piattelli, A. Microvessel density (MVD) and vascular endothelial growth factor expression (VEGF) in human oral squamous cell carcinoma. Anticancer Res., 2001, 21(1B), 689-695. Degidi, M.; Artese, L.; Rubini, C.; Perrotti, V.; Iezzi, G.; Piattelli, A. Microvessel density and vascular endothelial growth factor expression in sinus augmentation using Bio-Oss. Oral Dis., 2006, 12(5), 469-475. Aoyama, J.; Tanaka, E.; Miyauchi, M.; Takata, T.; Hanaoka, K.; Hattori, Y.; Sasaki, A.; Watanabe, M.; Tanne, K. Immunolocalization of vascular endothelial growth factor in rat condylar cartilage during postnatal development. Histochem. Cell Biol., 2004, 122(1), 35-40. Strocchi, R.; Orsini, G.; Iezzi, G.; Scarano, A.; Rubini, C.; Pecora, G.; Piattelli, A Bone regeneration with calcium sulfate: Evidence for increased angiogenesis in rabbits. J. Oral Implantol., 2002, 28(6), 273-278. Degidi, M.; Artese, L.; Rubini, C.; Perrotti, V.; Iezzi, G.; Piattelli, A. Microvessel density in sinus augmentation procedures using anorganic bovine bone and autologous bone: 3 months’ results. Implant Dent., 2007, 16(3), 317-325. Di Stefano, D.A.; Artese, L.; Iezzi, G.; Piattelli A.; Pagnutti, S.; Piccirilli, M.; Perrotti, V. Alveolar ridge regeneration with equine spongy bone: A clinical, histological, and immunohistochemical case series. Clin. Implant Dent. Relat. Res., 2009, 11(2), 90-100. Chaikof, E.L.; Matthew, H.; Kohn, J.; Mikos, A.G.; Prestwich, G.D.; Yip, C.M. Biomaterials and scaffolds in reparative medicine. Ann. NY Acad. Sci., 2002, 961, 96-105. Hammerle, C.H.F.; Chiantella, G.C.; Karring, T.; Lang, N.P. The effect of a deproteinized bovine bone mineral on bone regeneration around titanium dental implants. Clin. Oral. Implants Res., 1998, 9(3), 151-162. Traini, T.; Valentini, P.; Iezzi, G.; Piattelli, A. Histological and histomorphometrical evaluation of anorganic bovine bone retrieved 9 years after a sinus augmentation procedure. J. Periodontol., 2007, 78(5), 955-961. Iezzi, G.; Degidi, M.; Scarano, A.; Petrone, G.; Piattelli, A. Anorganic bone matrix retrieved 14 years after a sinus augmentation procedure: A histologic and histomorphometric evaluation. J. Periodontol., 2007, 78(10), 2057-2061.

Pe rs

[65]

Current Pharmaceutical Biotechnology, 2017, Vol. 18, No. 1

32 Current Pharmaceutical Biotechnology, 2017, Vol. 18, No. 1

[105]

[106]

phate biphasic bone graft material in maxillary sinus floor elevation: A radiographic study using 3D cone beam computed tomography. Clin. Oral. Implants. Res., 2016, 27(3), 348-353. Cancedda, R.; Cedola, A.; Giuliani, A.; Komlev, V.; Lagomarsino, S.; Mastrogiacomo, M.; Peyrin, F.; Rustichelli, F. Bulk and interface investigations of scaffolds and tissue-engineered bones by Xray microtomography and X-ray microdiffraction. Biomaterials, 2007, 28(15), 2505-2524. Renghini, C.; Giuliani, A.; Mazzoni, S.; Brun, F.; Larsson, E.; Baino, F.; Vitale-Brovarone, C. Microstructural characterization and in vitro bioactivity of porous glass-ceramic scaffolds for bone regeneration by synchrotron radiation X-ray microtomography. J. Europ. Ceramic Soc., 2013, 33(9), 1553-1565. Giuliani, A.; Manescu, A.; Larsson, E.; Tromba, G.; Luongo, G.; Piattelli, A.; Mangano, F.; Iezzi, G.; Mangano, C. In vivo regenerative properties of coralline-derived (biocoral) scaffold grafts in human maxillary defects: demonstrative and comparative study with Beta-tricalcium phosphate and biphasic calcium phosphate by syn-

[107]

[108]

[109]

chrotron radiation x-ray microtomography. Clin. Implant. Dent. Relat. Res., 2014, 16(5), 736-750. Kazakia, G.J.; Burghardt, A.J.; Cheung, S.; Majumdar, S. Assessment of bone tissue mineralization by conventional X-ray microcomputed tomography: Comparison with synchrotron radiation microcomputed tomography and ash measurements. Med. Physics, 2008, 35(7), 3170-3179. Giuliani, A.; Mazzoni, S.; Manescu, A.; Mohammadi, S.; Tromba, G.; Diomede, F.; Piattelli, A.; Trubiani, O. Osteoinductive properties study of collagenated Dual-Blocks by synchrotron radiation phase-contrast. Dent. Mater., 2014, 30(S1), e90-e91. Giuliani, A.; Manescu, A.; Langer, M.; Rustichelli, F.; Desiderio, V.; Paino, F.; De Rosa, A.; Laino, L.; d'Aquino, R.; Tirino, V.; Papaccio, G. Three years after transplants in human mandibles, histological and in-line holotomography revealed that stem cells regenerated a compact rather than a spongy bone: Biological and clinical implications. Stem Cells Transl. Med., 2013, 2(4), 316-324.

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[104]

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