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OBJECTIVE To assess the aetiologic factors, proposed diagnostic means and treatment strategies for neuralgia-inducing cavitational osteonecrosis. METHODS A search of the literature published up to June 2020 was conducted using Medline, the Cochrane Library, PsycINFO, CINAHL and Web of Science. The scientific quality of the evidence was rated according to NIH Quality Assessment Tools. RESULTS 4,051 articles were found, 59 were reviewed in full text, and 29 studies were included. With the exception of hereditary coagulopathies, which were identified as potential risk factors in five studies, suggestions concerning the aetiology varied widely. No gold standard diagnostic mean could be identified. Treatment was most often performed by surgical curettage of the affected bone. Surgical treatment outcomes were equally varied: significant facial pain remission was reported in 66%-100% for periods varying between 2 months to 18 years, whereas no or little relief and recurrences were reported in up to ⅓ of cases. All studies were observational in their design. All investigations were rated as poor quality because of high risk of bias and non-transparent reporting. CONCLUSIONS Evidence concerning the aetiology, diagnosis and treatment of NICO is poor. Prospective diagnostic and therapeutic studies are needed before the usefulness of invasive therapeutic procedures can be evaluated.

Face-bow transfer is an essential step in articulator-based orthognathic surgery planning. However, it can be a source of inaccuracy. Virtual computer-based planning avoids this error through the use of direct patient-related three-dimensional imaging data. The aim of this prospective observational study was to determine the error of face-bow transfer three-dimensionally and correlate it to the different types of malocclusion. Orthognathic surgery performed on 38 patients (10 male, 28 female; mean (standard deviation) age 24.7 (6.9) years) was planned twice: first articulator-based with plaster models and second computer-based with surgery planning software. Both models were digitized and compared regarding the angle between the Frankfort horizontal plane and the occlusal plane. In most cases, the angle in the sagittal dimension was higher in the articulator-based model than in the computer-based model. The angle in the transverse dimension was as often under- as over-represented. The type of malocclusion, i.e. skeletal class, vertical relationship, and degree of asymmetry, had no significant impact on the amount of error. In conclusion, this study indicates that computer-based planning should be considered as an advantageous alternative in orthognathic surgery planning.

Oral cancer therapy is associated with a loss in health-related quality of life (HRQOL) and can also lead to post-traumatic growth (PTG). The current study analyzed the relationship between HRQOL, PTG and influencing clinical factors after treatment. The coherent clinical data of 15 patients were retrospectively analyzed over a 1-year study period. HRQOL and PTG were studied using the University of Washington Quality of Life Version 4 (UW-QOL v4) and Posttraumatic Growth Inventory (PTGI) questionnaires. The results revealed that HRQOL was significantly decreased in a pre- to postoperative manner (P=0.011). Sex demonstrated a nearly significant effect on HRQOL (P=0.058). PTG was experienced the most after surgery, and continuously decreased over the 1-year study period. Patient age had a significant effect on PTG (P=0.040). A significant correlation was also established between HRQOL and PTG (P

Objectives This publication reports on the EAO workshop group 1 summaries, discussions and consensus statements based on four systematic reviews evaluating the impact of timing of dental implant placement and loading. Materials and methods The first of the systematic reviews was on the influence of the timing of implant placement and loading in the biological outcomes of implant-supported fixed partial dentures. The second systematic review evaluated the influence of the timing of implant placement and loading on the aesthetic outcomes in single-tooth implants. The third systematic review was on the long-term outcomes of maxillary single-tooth implants in relation to timing protocols of implant placement and loading and the fourth on patient's perception of timing concepts in implant dentistry. The group evaluated these systematic reviews, provided comments and additions as required and agreed on the relevant consensus statements as well as on clinical and research recommendations. Results Different timings of implant placement/loading presented with high implant survival rates. The systematic reviews evaluated from this working group provided a number of conclusions based on the available/current literature. However, the specific topic of timing is an area that further research is required in order to provide detailed guidelines for the different protocols to be employed.

Objectives Sufficient dental decompensation is crucial for treatment success in combined orthodontic-surgical treatment. The study’s objective was to determine the treatment success and efficiency in sagittal, vertical, and transversal decompensation. Methods This longitudinal, observational study enrolled 52 adult patients, who underwent orthodontic-surgical treatment. Incisor inclinations and positions as well as skeletal changes were assessed pre-treatment (T1), pre-surgical (T2), and post-surgical (T3) by lateral cephalograms and CBCT scans. Results Incisor decompensation was insufficient in all three dimensions. Sagittal: treatment efficiency did not differ between class II and III patients. Vertical: patients with open bite demonstrated pre-surgical bite deepening and insufficient surgical reduction of the maxillomandibular plane angle. Transversal: Dental midline deviations were not adapted to the skeletal asymmetry so that menton deviations were not properly corrected. Conclusions Incisor decompensation was not as successful as requested in all three dimensions and the treatment ideal was seldom achieved. Clinical relevance To improve the skeletal outcome, the orthodontist has to treat the patient with the desired surgical movements in mind and should critically evaluate the pre-surgical incisor decompensation before referral to the surgical team.

Background and Aims To review the regenerative technologies used in bone regeneration: bone grafts, barrier membranes, bioactive factors and cell therapies. Material and Methods Four background review publications served to elaborate this consensus report. Results and Conclusions Biomaterials used as bone grafts must meet specific requirements: biocompatibility, porosity, osteoconductivity, osteoinductivity, surface properties, biodegradability, mechanical properties, angiogenicity, handling and manufacturing processes. Currently used biomaterials have demonstrated advantages and limitations based on the fulfilment of these requirements. Similarly, membranes for guided bone regeneration (GBR ) must fulfil specific properties and potential biological mechanisms to improve their clinical applicability. Pre‐clinical and clinical studies have evaluated the added effect of bone morphogenetic proteins (mainly BMP ‐2) and autologous platelet concentrates (APC s) when used as bioactive agents to enhance bone regeneration. Three main approaches using cell therapies to enhance bone regeneration have been evaluated: (a) “minimally manipulated” whole tissue fractions; (b) ex vivo expanded “uncommitted” stem/progenitor cells; and (c) ex vivo expanded “committed” bone‐/periosteum‐derived cells. Based on the evidence from clinical trials, transplantation of cells, most commonly whole bone marrow aspirates (BMA ) or bone marrow aspirate concentrations (BMAC ), in combination with biomaterial scaffolds has demonstrated an additional effect in sinus augmentation and horizontal ridge augmentation, and comparable bone regeneration to autogenous bone in alveolar cleft repair.

OBJECTIVES: The task of this working group was to update the knowledge about the use of drugs and biologicals affecting healing of soft tissue and bone during implant treatment or procedures associated with it. Moreover, the impact of titanium particles and biocorrosion on complications and implant survival has been analysed. MATERIALS AND METHODS: The literature in the areas of interest (platelet concentrates, antiresorptive drugs as well as implant-host interaction) was screened using systematic reviews for the former two areas, whereas a narrative critical review was performed for the latter topic. Two manuscripts on platelet concentrates, one manuscript on antiresorptive drugs and one manuscript on the effects of biocorrosion, were presented for group analysis with subsequent discussion in the plenum and final consensus approval. RESULTS: Results and conclusions of the individual reviews of the three topics are presented in the respective papers. Conclusions of the group on strengths and weaknesses of available evidence as well as consensus statements and directions for further research are provided in this study. The following papers were subject to group discussions and formed the basis for the consensus statements: Stähli A, Strauss FJ, Gruber R. () The use of platelet-rich-plasma to enhance the outcomes of implant-related therapies: a systematic review Strauss FJ, Stähli A, Gruber R. (2018) The use of platelet-rich-fibrin to enhance the outcomes of implant-related therapies: a systematic review Mombelli A, Hashim D, Cionca N. () What is the impact of titanium particles and bio-corrosion on implant survival and complications? A critical review Stavropoulos A, Bertl K, Pietschmann P, Pandis N, Morten Schiødt, Klinge B. () The effect of antiresorptive drugs on implant therapy: a systematic review. ispartof: CLINICAL ORAL IMPLANTS RESEARCH vol:29 pages:93-99 ispartof: location:SWITZERLAND, Pfaffikon status: published

Article, editorial letter

This study investigated the cotransplantation of bone marrow mesenchymal stromal cells (BMSC) and human umbilical cord endothelial cells (HUVEC), and evaluated their contribution to vascular and bone tissue engineering in vivo. To evaluate the success of osteogenic differentiation and timely vascularization of different osteoconductive scaffolds in vivo, we transferred BMSC and HUVEC pre-cultivated calcium carbonate (CaCO3) and hydroxylapatite (HA) matrices into immunocompromised RNU-rats, and analyzed mineralization, expression of osteopontin, and vascular integration via new vessel formation. After in vivo transplantation, pre-cultivated scaffolds demonstrated overall improved mineralization of 44% for CaCO3 (p = 0.01, SD ± 14.3) and 34% for HA (p = 0.001, SD ± 17.8), as well as improved vascularization of 5.6 vessels/0.1 mm2 on CaCO3 (p There is an increasing demand for improved bone regeneration in tissue engineering. Cotransplantation of mesenchymal stromal cells and endothelial cells often demonstrates synergistic improvements in vitro. However, the benefits or superiority of cotransplantation was not evident in vivo and so will require further investigation.

Incorrect registration of the condylar position in orthognathic surgery is supposed to cause postoperative relapse, condylar resorption and temporomandibular disorders. The aim of this prospective study was to evaluate the influence of general anaesthesia on centric relation (CR). Therefore, CR registered preoperatively in the awake patient and CR registered intraoperatively under general anaesthesia were recorded in 30 patients (14 men, 16 women) undergoing orthognathic surgery (skeletal class I: n=3, II: n=13, III: n=14; symmetric: n=20; asymmetric: n=10). CR records were digitized and, through superimposition on the preoperative cone beam computed tomography of the patient's skull, the superior, anterior and posterior joint space and the volumetric congruence of 120 condyles were analysed. The linear measurements of joint spaces did not demonstrate any clinically relevant discrepancy between the CR measured in the awake and anaesthetized patient. In contrast, volumetric analysis revealed statistically significant differences between both states, with an intraoperative condylar sag predominantly in the posterior-inferior direction. The patient's skeletal class or symmetry had no significant influence on the intraoperative condylar displacement. Thus, the risk of fixing the condyle in an unphysiological position supports the idea of using intraoperative condylar positioning devices to achieve predictable and stable outcomes.

BACKGROUND: The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow-up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL). METHODS: Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias. RESULTS: There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL. CONCLUSION: There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL. peerReviewed

Objective We compared the intraindividual effects of increasing zoledronic acid (ZA) concentrations on osteoblast-like cells with different embryologic origins. Study Design Cultured osteoblast-like cells from mandible and iliac crest bone samples of domestic pigs were exposed to increasing concentrations of ZA (0, 10 −8 , 10 −6 , and 10 −4 M). Proliferation was assessed by cell counting. Receptor activator of nuclear factor kB ligand and osteoprotegerin (OPG) messenger RNA expression were assessed at 0, 1, 4, 7, and 10 days. Results The OPG expression level was higher in the iliac crest than in the mandible. Neither ZA concentration nor the cells' origin affected the expression of receptor activator of nuclear factor kB ligand. At 10 −6 M, OPG expression from both locations reached the same level after 7 days of cultivation, as OPG expression increased to a greater extent in the mandible in comparison to the iliac crest. Conclusion Cultured mandibular osteoblast-like cells reacted more sensitively to high ZA concentrations than did osteoblast-like cells from the iliac crest.

Tumour progression in head and neck squamous cell carcinoma (HNSCC) is influenced by the surrounding stroma and inflammatory cytokines such as tumour necrosis factor alpha (TNF-α). The aim of this study was to test the hypothesis that TNF-α modulates the interactions of HNSCC cell line PCI-13 and bone marrow mesenchymal stromal cells (BMSCs) and influences markers of epithelial-mesenchymal transition (EMT). Following induction with TNF-α, mono- and co-cultures of BMSCs and the established HNSCC cell line PCI-13 were analyzed; protein expression of E-cadherin and vimentin and qRT-PCR expression of Snail, Twist, MMP14, vimentin, E-cadherin, and β-catenin were examined, and changes in cellular AKT signalling were analyzed. TNF-α induced a significant decrease in E-cadherin (64.5±6.0%, P=0.002) and vimentin (10.4±3.5%, P=0.04) protein expression in co-cultured PCI-13, while qRT-PCR showed a significant increase in β-catenin (BMSCs P

INTRODUCTION: The oral squamous cell carcinoma (OSCC) is a leading cause of death in human malignancies. The aim of this study is to integrate the CAM Assay as a reliable and good working in vivo model for the evaluation of OSCC tumor samples and its growth into the clinical work flow. MATERIAL AND METHODS: Fresh human Tumor samples (OSCCs) 1 x 1 cm in size were cut into 350-450 mu m thick slices by a Vibratome and put on the prepared CAM model. After growth of the tumor tissue on the CAM, we started with topical induction of proinflammatory cytokines (TNF alpha) and growth factors (TGF beta). After further growth of the tumor on the assay, we explanted the tumor tissue and first performed microscopic and then immunohistochemical examinations. E-cadherin and vimentin were used as Epithelial-to-mesenchymal transition (EMT) -makers and the histologic preparations were evaluated histomorphometrically. The results were correlated with clinical parameters of the patients. RESULTS: Small tumors (T1 / T2) show higher E-cadherin expression than larger tumors (T3 / T4) (p = 0.01). The additional stimulation with TNF alpha or TGF beta has no additional inductive effect. Even the stimulation with TNF alpha repectively TGF beta lead to a higher E-cadherin expression in smaller tumors (T1 / T2). The Vimentin expression is the opposite. Depended on the patients N-Stage a trend towards an increase in the E-cadherin expression in N1 / 2 and diminished E-cadherin expression in N0 patients could be seen. There is no change with TGF beta in NO and N1 / 2 patients. Vimentin was reduced in the N0 group and expressed more frequently in the N1 / N2b group. An induction with both TNF alpha and TGF beta resulted in an increased expression of Vimentin in the N1 / N2b stages. CONCLUSION: By integrating a CAM assay into the clinical workflow, tumors with preserved tumor architecture can be cultured and subjected to histological and molecular biology studies. Effects on biological behavior are recognizable and demonstrable in this model. The key markers E-cadherin and vimentin alone are not sufficient to represent the complexity of the EMT in this model. Further molecular biology and signaling pathway analyzes are necessary.

Background: Little is known about the physical symptoms and psychosocial burden of patients at the time of diagnosis of an incurable situation, although cancer treatment guidelines demand early assessment and integration of palliative care concepts, beginning from the diagnosis of incurability. Methods: Therefore, we initiated a prospective longitudinal multicenter cohort study assessing the symptoms and needs of patients suffering from incurable cancer (various entities), from the time of diagnosing incurability (i.e., before palliative anticancer treatment was initiated) and in 3-monthly intervals thereafter, by using validated self-reporting tools. Here, we focus on patients with head and neck cancer and present preliminary results on symptoms and need prevalences, on clinical implications, and on the feasibility of a methodologically complex assessment procedure in a particularly vulnerable study population. Results: 22 patients completed the first visit. The Eastern Cooperative Oncology Group (ECOG) performance scores and most physical symptoms and psychosocial items varied between the extremes, from a virtually uncompromised condition to extremely perceived symptoms and needs. If intense face-to-face study support was provided, the study concept proved to be feasible, despite the complexity of assessment, problems in interdisciplinary and patient communication, comorbidities, and early death from complications. Conclusions: The striking variability in the perceived symptom and need intensities requires a highly individualized approach. For clinical purposes, a less complex screening procedure would be desirable, in order to enable a routine, early and comprehensive support, including palliative care services.

The use of ultrasound to cut bone in oral and craniofacial surgery has increased. There is concern that the application of ultrasound to the craniofacial skeleton might represent a potential hazard to the inner ear because of sound transmission by bone conduction resulting in hearing trauma. Conventional and ultrasound osteotomies were performed on human specimens of temporal bone containing an intact middle and inner ear. The equivalent sound pressure was measured with a microphone at the round window, which had been calibrated with a bone conduction audiometer. Conventional osteotomy with a rose burr resulted in maximum sound pressures of 125dB(A) consisting of major frequency components at 2100, 7600, and 9300Hz. Ultrasound osteotomy resulted in maximum sound pressures of 122dB(A) and exhibited major frequency components at around 10kHz, 20kHz, and 26.5kHz. Ultrasound osteotomies have no acoustic advantage over conventional osteotomies. Both osteotomy techniques can produce noise-induced hearing trauma, especially when applied over longer durations of time. This appears to be more relevant for ultrasound osteotomies, because the bone cutting efficiency is usually poorer than in conventional osteotomies. Surgeons should consider the risk of noise-induced potential damage to the inner ear when selecting the method of osteotomy.

Even though modern surgical techniques are dominating reconstructive facial procedures, the capability to use facial epitheses for reconstruction is still an important skill for the maxillofacial surgeon. We present an international multicenter analysis to clarify which techniques are used to fixate facial prostheses. We contacted all maxillofacial departments in Germany, Austria, Switzerland and Norway which were registered with the German society for oral and maxillofacial surgery (DGMKG). These centers were asked via electronical mail to provide information on the type of epithesis fixation systems currently in use. The return rate from 58 departments was 43.1% (n = 25). Overall, implant fixation was the preferred fixation system (92%). Plates were the second most common fixation technique (32%). No centers reported the standard use of non-invasive fixation techniques for permanent epithesis fixation. The main retention systems in use were magnets (24/25), other retention systems are used much less often. The current preferred fixation technique for facial epitheses consists of implant-based, magnet-fixated epitheses. For nasal prostheses, a plate-based, magnet-fixated system is often used.

The submental island flap has become increasingly popular in the treatment of intraoral defects following tumor ablation. However, there was concern that the elevation of the pedicled flap might interfere with the efficiency of level I-lymph node dissection and decrease the oncologic prognosis of the patients.In a prospective clinical study over five years the outcome of 45 consecutive patients with intraoral cancer of various T-stages treated with submental island flaps was evaluated and compared to 45 patients with a T-status analogous oral cancer treated with free radial forearm flaps.All submental island flaps beside three were successful (93.3%). The obtained functional results were pleasing and the donor morbidity low. Patients treated with submental island flaps exhibited no enhanced risk of local tumor recurrence or lymph node metastasis (p0.86). In contrast, the operation time, time of intensive care and hospitalization were reduced (p0.001).We conclude that the submental island flap is an effective and predictable option of small and medium-sized oral defect treatment. It is a valuable alternative to free flap soft tissue reconstructions such as radial forearm or perforator flaps. It seems particularly beneficial to patients with relevant comorbidities as often present in the oral cancer population. The application of the submental island flap does not reduce the oncological prognosis of oral cancer patients.

The aim of the present study was to test the hypothesis that immobilisation of bone morphogenic proteins on the surface of titanium implants through nano-anchored oligonucleotides can enhance peri-implant bone formation. Non-coding 60-mer DNA oligonucleotides (ODN) were anchored to the surface of custom made sandblasted acid etched (SAE) titanium screw implants through anodic polarisation, gamma-sterilised with a standard dose of 25 kGy, and were hybridised with complementary 30-mer strands of DNA oligonucleotides conjugated to rhBMP2. Blank SAE implants, SAE implants with nano-anchored ODN and SAE implants with nano-anchored ODN and non-conjugated rhBMP2 served as controls. The implants were inserted into the tibiae of 36 Sprague Dawley rats. Perforations at the head and the tip of the implants allowed for bone ingrowth. Bone ingrowth into perforations and bone implant contact (BIC) as well as bone density (BD) at a distance of 200 µm from the implant surface were assessed after 1 , 4 and 13 weeks. Implants with nano-anchored ODN strands hybridised with conjugated rhBMP2 exhibited enhanced bone ingrowth into the perforations and increased BIC after 1 week as well as increased BIC after 4 weeks compared to controls. No difference was seen after 13 weeks. Bone density around the outer implant surface did not differ significantly at any of the intervals. It is concluded that rhBMP2 immobilised on the surface of titanium implants through nano-anchored oligonucleotide strands can enhance bone implant contact. The conditions of sterilisation tested allowed for handling under clinically relevant conditions.

This clinical trial aimed to test the hypothesis that piezosurgery causes reduced nerval irritations and, thus, reduced somatosensory impairment when used in orthognathic surgery of the mandible.To this end, 37 consecutive patients with Angle Class II and III malocclusion were treated using bilateral sagittal split osteotomies (BSSO) of the mandible. In a split mouth design, randomized one side of the mandible was operated using a conventional saw, while a piezosurgery device was used on the contralateral side. In order to test the individual qualities of somatosensory function, quantitative sensory testings (QSTs) were performed 1 month, 6 months and 1 year after surgery.A comparison of the data using a two-way analysis of variance (ANOVA) revealed a significant reduction in postoperative impairment in warm detection threshold (WDT) (P = 0.046), a decreased dynamic mechanical allodynia (ALL) (P = 0.002) and a decreased vibration detection threshold (VDT) (P = 0.030) on the piezosurgery side of the mandible as opposed to the conventionally operated control side. In the remaining QSTs, minor deviations from the preoperative baseline conditions and a more rapid regression could be observed.Piezosurgery caused reduced somatosensory impairment and a faster recovery of somatosensory functions in the present investigation.

Aims To test the immobilization of vascular endothelial growth factor (VEGF165) on the surface of titanium implants using DNA oligonucleotide (ODN) anchor strands for the ability to enhance periimplant bone formation. Materials and Methods DNA oligonucleotides were anchored to the surface of sandblasted acid-etched (SAE) titanium screw implants and were hybridized with complementary strands of ODN conjugated to rhVEGF165. The implants were tested against blank SAE implants and SAE implants with nano-anchored ODN. The implants were inserted into the tibiae of 36 Sprague–Dawley rats. Primary outcome parameters were bone-implant contact (BIC), amount of new bone formation and periimplant bone density (BD). density after 1, 4 and 13 weeks. Unit of analysis has been the individual implant. Results Implants with rhVEGF165 hybridized to ODN anchor strands exhibited significantly increased average BIC after 1 month compared to blank implants and implants with anchored ODN strands. Conclusions It is concluded that rhVEGF165immobilized on the surface of titanium implants through nano-anchored oligonucleotide strands can accelerate BIC of sandblasted and etched titanium implants to a certain extent. The radius of effect of the growth factor appears to be limited to tissue immediately adjacent to the implant surface.

The aim of this study was to evaluate and compare the quality of systematic reviews of vertical bone regeneration techniques, using two quality-assessment tools (AMSTAR and ROBIS). An electronic literature search was conducted to identify systematic reviews or meta-analyses that would evaluate at least one of the following outcomes: implant survival, success rates, complications or bone gain after vertical ridge augmentation. Methodological quality assessment was performed by two independent evaluators. Results were compared between reviewers, and reliability measures were calculated using the Holsti’s method® and Cohen’s kappa. Seventeen systematic reviews were included, of which seven presented meta-analysis. Mean ±95% confidence interval AMSTAR score was 6.35 [4.74;7.97], with higher scores being correlated with a smaller risk of bias (Pearson’s correlation coefficient = −0.84; P < 0.01). Cohen’s inter-examiner kappa showed substantial agreement for both checklists. From the available evidence, we ascertained that, regardless of the technique used, it is possible to obtain vertical bone gains. Implant success in regenerated areas was similar to implants placed in pristine bone with results equating between 61.5% and 100% with guided bone regeneration being considered the most predictable technique regarding bone stability, while distraction osteogenesis achieved the biggest bone gains with the highest risk of possible complications. Sin financiación 2.068 JCR (2019) Q2, 33/91 Dentistry, Oral Surgery & Medicine 1.020 SJR (2019) Q1, 9/49 Oral Surgery No data IDR 2018 UEM

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery.

AimTo test the hypothesis that the addition of small amounts of rhVEGF to rhBMP2 in a polymer carrier can accomplish equivalent repair effect as a reduced dosage of rhBMP2 compared to rhBMP2 alone. Materials and MethodsDefects were created bilaterally in the mandibles of 18 minipigs. In 12 test animals, defects were filled with 0.5g particulate PDLLA/CaCO3 composite loaded with 400g rhBMP2/50g rhVEGF165 on one side and 800g rhBMP2 on the other. After 4 and 13weeks, the animals were evaluated each for area of new bone formation (mm(2)) and bone density (area %). ResultsArea of newly formed bone was higher in defects with carriers loaded with 400g rhBMP2 50 mu g VEGF165 than in defects with 800g rhBMP2 after 4weeks (11.97 versus 7.97mm(2);p=0.043) and 13weeks (72.48 versus 62.2mm(2);p=.028). Defects filled with blank carrier exhibited less bone after 13weeks (42.75mm(2);p=.039 and .020 respectively). ConclusionsDelivery of rhBMP2 from a polymer carrier can improve repair of large saddle defects of the mandibular ridge. Addition of small amounts of rhVEGF can increase bone formation and at the same time reduce the dosage of rhBMP2.

Dental implants are one of the most frequently used treatment options for tooth replacement. Approximately 30% of patients with dental implants develop peri-implantitis, which is an oral inflammatory disease that leads to loss of the supporting tissues, predominately the bone. For the development of future therapeutic strategies, it is essential to understand the molecular pathophysiology of human dental peri-implant infections. Here, we describe the gene and protein expression patterns of peri-implantitis bone tissue compared with healthy peri-implant bone tissue. Furthermore, cells from the osteoblastic lineage derived from peri-implantitis samples were immortalized and characterized. We applied microarray, quantitative reverse transcription polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. The levels of typical bone matrix molecules, including SPP1, BGLAP, and COL9A1, in patients with peri-implantitis were reduced, while the inflammation marker interleukin 8 (IL8) was highly expressed. RUNX2, one of the transcription factors of mature osteoblasts, was also decreased in peri-implantitis. Finally, the human telomerase reverse transcriptase immortalized cell line from peri-implantitis exhibited a more fibro-osteoblastic character than did the healthy control.

Incorporation of alkaline nano-/microparticles for neutralization of acidic degradation products into degradable polymer foams requires the use of organic solvents, which may compromise biocompatibility and may be associated with biological hazards. The aim of the present study was to develop and validate a solvent-free method to produce porous poly (DL-lactic acid)/calcium carbonate composite scaffolds (PDLLA/CaCO3) for controlled release of incorporated osteogenic growth factors. Composite PDLLA/CaCO3 granules were produced using a milling process and compared to composite material fabricated through a solution precipitation process using organic solvents. Particle size and mineral content were comparable in both groups. Supercritical carbon dioxide pressure was used to incorporate rhBMP2 into both composites. Gas foaming resulted in comparable pore structures in both groups exhibiting a homogenous distribution of CaCO3 microparticles in the polymer scaffolds. The elasticity modulus of both types of scaffolds was not significantly different whereas the bending strength of the solvent-free produced scaffolds was significantly lower. The pH values remained constant between 6.90 and 7.25 during degradation of both composites. Release of BMP2 was significantly higher and the induction of alkaline phosphatase was more reliable in the group of scaffolds produced without organic solvents. Solvent-free fabrication of composite PDLLA/CaCO3 scaffolds for controlled release of bone growth factors through gas foaming significantly enhances the release of growth factors and improves the biological efficacy of the incorporated growth factors.

Objectives The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) induces an increased and homogenous distribution of new bone formation across the entire volume of sinus floor augmentation in 12 Goettingen Minipigs. Material and Methods In a randomized split-mouth design, one maxillary sinus was augmented with the bone substitute β-TCP, whereas a combination of β-TCP and the osteoinductive growth factor rhGDF-5 was used on the contralateral side. To evaluate the influence of dose and time on the effectiveness of the factor, two different concentrations of rhGDF-5 (400 μg and 800 μg) and healing periods (4 and 12 weeks) were each analysed. Results After 4 weeks, a homogenous gradient of bone formation could be observed for all dosage groups, with decreasing bone density from the local bone towards the sinus membrane. Both test groups, however, achieved a higher total level of bone formation compared with the control group, which was only significant in the low-dose group (P = 0.0184). After 12 weeks, the influence of the growth factor significantly depends on the region (P = 0.023). In the low-dose group, the new bone formation did not differ significantly within the examined regions of the graft (P = 0.1118), suggesting a homogeneous bone formation over the entire augmentation. The gradient of the high-dose group was similar to the control group with a decrease of local bone development. Conclusions rhGDF-5 delivered on a β-TCP scaffold material leads to an increase in homogeneous new bone formation across the entire volume of the sinus floor augmentation.

UNLABELLED The soft tissues around dental implants are enlarged compared with the gingiva because of the longer junctional epithelium and the hemidesmosonal attachments are fewer, suggestive of a poorer quality attachment. Inflammatory infiltrates caused by bacterial colonization of the implant-abutment interface are thought to be one of the factors causing epithelial downgrowth and subsequent peri-implant bone loss. Gold alloys and dental ceramics as well as the contamination of the implant surface with amino alcohols, appear to promote epithelial downgrowth. Physical manipulaton of the abutment surfaces, including concave abutment designs, platform switching, and microgrooved surfaces are believed to inhibit epithelial downgrowth and minimizes bone loss at the implant shoulder. This paper reviews the factors that are believed to influence the migration of epithelial attachment the dental implant and abutment surfaces. Exploration of innovative computer-aided design/computer-aided manufacturing-based concepts such as "one abutment-one time" and their effect on epithelial downgrowth are discussed. CLINICAL SIGNIFICANCE Based on the review of current literature, the authors recommend inserting definitive abutments at the time of surgical uncovering. To implement this concept, registration of the implant position should to be taken at the time of surgical implant placement.

Purpose Provide a comprehensive overview on the clinical use and the efficacy of growth factors in different reconstructive procedures in the oral maxillofacial area. Materials and Methods A systematic review of the literature on the clinical use of human and human recombinant growth factors in oral maxillofacial reconstruction has been performed. Results The use of autogenous growth factors in platelet concentrates (PCs) has shown to be beneficial in the treatment of intrabony pockets at a reasonable level of evidence by improving probing depth and clinical attachment levels as well as linear bone fill within the limits of the observation periods. The application in conjunction with non-autogenous graft materials has been superior to the use of PCs only or grafting materials alone. No benefits have been shown for the use of PCs in recession treatment. When used in furcation treatment, probing depth, clinical attachment level and linear bone fill have been reported to improve significantly, however, without clinical benefit. No benefit for the final outcome could be shown for the use of PCs neither in sinus lift procedures nor in lateral / vertical crest augmentations. The use of human recombinant growth factors has been so far limited almost exclusively to rhPDGF-BB and rhBMPs (BMP-2, BMP-7 and GDF-5). The use of rhPDGF in the treatment of intrabony pockets has shown a reliable increase in linear bone fill but weaker evidence for permanent improvements of clinical attachment level. So far there is no evidence to support the use in recession treatment, sinus lift procedures and socket healing as well as lateral / vertical augmentations of the alveolar crest. rhBMPs have shown to be effective in enhancing bone formation in socket healing (rhBMP-2) and sinus lift procedures (rhBMP-2 and GDF-5). No controlled studies are available for the use in mandibular segmental repair. Successful reports on this application appear to be limited to primary reconstruction after ablative surgery for benign pathology with preservation of the periosteum. Conclusion Evidence of clinical efficacy of growth factors in reconstructive procedures in the oral and maxillofacial area is limited.

Aim The aim of the present study was to evaluate bone formation in vertical ridge augmentations using particulate bone grafting material stabilized by a resorbable polymer. Material and methods Three vertical defects were created in the maxillary alveolar ridge of six Beagle dogs 3 months after the removal of all premolars. One defect in each dog was filled with tricalciumphosphate/hydroxylapatite (TCP/HA) grafting material and stabilized using a poloxamer hydrogel (test group). Defects filled with grafting material only and covered with a collagen membrane as well as empty defects served as controls (controls 1 & 2). Bone formation in the defects was evaluated after 14 weeks of healing using histomorphometry on undecalcified thick-section specimens. Results There was no difference between the test group and the controls with respect to the amount of newly formed bone, percentage of bone fill, and bone density. The mean maximum bone height within the augmented area was the only parameter that was significantly higher in the test group compared with empty defects. The use of the poloxamer gel did not result in a better preservation of ridge shape compared with the group of augmentations covered with a collagen membrane. Conclusions The use of a poloxamer gel for the stabilization of particulate bone grafting material in vertical ridge augmentations had no advantage compared with coverage of grafting materials with a collagen membrane.

The aim of the present study was to evaluate the effect of different dosages of retarded vs. rapid release of bone morphogenic protein 2 (BMP2) at different recipient sites. Porous composite poly(D,L-lactic acid) (PDLLA)/CaCO3 scaffolds were loaded with three different dosages of rhBMP2 (24 µg, 48 µg and 96 µg) and implanted, together with blank controls, both into non-healing defects of the mandibles and into the gluteal muscles of 24 adult male Wistar rats. After 26 weeks, bone formation and expression of bone specific markers [alkaline phosphatase (AP) and Runx2] were evaluated by histomorphometry and immunohistochemistry. Results showed that the mode of delivery had no quantitative effect on bone formation in mandibular sites. Expression of AP and Runx2 showed significant differences among the three dosage groups. There were significant correlations between the expression of both AP and Runx2 as well as the extent of bone formation, with both retarded and rapid release of rhBMP2. In ectopic sites, retarded release significantly enhanced bone formation in the low and medium dosage groups, compared to rapid release. Expression of AP was significantly higher and Runx2 significantly lower in ectopic sites, compared to mandibular sites. Significant correlations between the expression of bone specific markers and bone formation occurred only in the retarded delivery groups, but not in the rapid release groups. Within the limitations of the experimental model, it was concluded that retarded delivery of BMP2 was effective, preferably in sites with low or non-existing pristine osteogenic activity. Expression of bone specific markers indicated that osteogenic pathways might be different in mandibular vs. ectopic sites. peerReviewed

Purpose Adenoid cystic carcinomas are rare malignant tumors of the salivary glands. They are characterized by a high rate of local recurrence, late distant metastasis and a poor disease-free survival. In this study, we analyzed a series of 61 patients who were all treated at the University of Gottingen over a period of 21.0 years. Materials and methods In all 61 patients with salivary adenoid cystic carcinoma, clinical data, demographic data, risk factors, tumor location, tumor stage, status of surgical margin, surgical treatment, postoperative radiotherapy and follow-up interval were assessed. Results The overall survival (OS) and the disease-free survival (DFS) of patients who underwent surgery and those who underwent combined surgery with radiotherapy showed no significant differences. Neither did the T-stage (T1/T2 vs. T3/T4) show significant differences in OS and DFS. Only the status of the surgical margin was significantly associated with a longer OS and a longer DFS. Conclusion The present results confirm that the radical surgical resection with clear tumor-free margins is the most important predictor for a longer survival. Adjuvant radiotherapy should be discussed from case to case, but should not be seen as an absolute prognostic factor for OS.

Purpose To evaluate the efficacy of grafting materials in lateral and vertical ridge augmentations. Materials and methods A systematic review of the literature on the clinical use of grafting materials of the years 1995 to April 2015 was conducted using electronic search of PubMed and Cochrane libraries and hand search of eight print journals. A total of 184 papers were included, comprising 6182 patients. Parameters evaluated were observation period [months], bone formation [histologic area%], defect fill [%], horizontal and vertical gain [mm], loss of augmented volume [mm], complication rate [%], and implant survival rate [%]. Results are expressed as weighted means ± SD. Results Results were obtained after a weighted mean observation period of 27.4 months (range 3–168 months). Bone formation in the augmented areas varied from 33.2 ± 14.9% for allogeneic grafts to 56.0 ± 25.6% for mixtures of autogenous and other grafting materials. Defect fill in dehiscence defects ranged from 51.0 ± 13.6% (synthetic) to 85.8 ± 13.4% (xenogeneic) for the different materials, with an overall weighted mean of 79.8 ± 18.7%. Weighted mean horizontal gain for all particulate grafting materials was 3.7 ± 1.2 mm, with variation between 2.2 ± 1.2 mm (synthetic) and 4.5 ± 1.0 mm (mixtures of autogenous bone with allogeneic/xenogeneic grafting material) without statistical significance. Weighted overall mean vertical gain was 3.7 ± 1.4 mm. Vertical gain was substantially higher when space-making barrier materials such as titanium meshes were used; however this was also associated with strong increase in complication rate. Block grafts achieved higher horizontal gain by approximately 1 mm. The use of block grafts achieved significantly increased vertical gain compared to particulate material only when autogenous block grafts from extraoral donor sites were used. Conclusion Horizontal and vertical gain by 3.7 mm on average can be achieved using particulate materials. This can be increased by using titanium meshes. Substantial vertical gains beyond this dimension require the use of extraoral bone block grafts.

The present study aimed to evaluate primary stability (PS) and osseointegration of dental implants in polylactide [70/30 poly(l-lactide-co-d, l-lactide); (PLDLA)] modified bone in 30 Goettingen minipigs. Each animal received three implants per jaw quadrant. In a split-mouth design, one side of the maxilla and mandible was randomly allocated to the experimental treatment (PLDLA applied into the drill hole before implantation), while the contralateral sides served as intraindividual controls (no PLDLA applied). The required insertion torque and the implant stability quotient (ISQ) were measured during implantation. ISQ, volume density (VD) of new bone formation (NBF), and the bone-implant contact (BIC) were evaluated at the end of the observation period (1, 3, 6, 12, and 24 months, respectively) in six animals each. Across all study groups, the PLDLA treatment resulted in a) a comparable insertion torque, b) an equivalent ISQ, c) a reduced BIC, and d) a reduced VD of NBF, as opposed to the untreated controls. In conclusion, the PLDLA treatment did not affect the PS, but rather led to an impaired osseointegration, which was particularly strong in the compact mandibular bone, and decreased in the spongious maxillary bone. PLDLA induced anchoring in spongious bone should be evaluated in further investigations.

Schliephake H, Hefti T, Schlottig F, Gedet P, Staedt H. Mechanical anchorage and peri-implant bone formation of surface-modified zirconia in minipigs. J Clin Periodontol 2010; 37: 818–828. doi: 10.1111/j.1600-051X.2010.01549. Abstract Aim: To test the hypothesis that peri-implant bone formation and mechanical stability of surface-modified zirconia and titanium implants are equivalent. Materials and Methods: Twelve minipigs received three types of implants on either side of the mandible 8 weeks after removal of all pre-molar teeth: (i) a zirconia implant with a sandblasted surface; (ii) a zirconia implants with a sandblasted and etched surface; and (iii) a titanium implant with a sandblasted and acid-etched surface that served as a control. Removal torque and peri-implant bone regeneration were evaluated in six animals each after 4 and 13 weeks. Results: The titanium surface was significantly rougher than both tested zirconia surfaces. Mean bone to implant contact (BIC) did not differ significantly between the three implant types after 4 weeks but was significantly higher for titanium compared with both zirconia implants after 13 weeks (p

The aim of the present study was to test the hypothesis that calcium phosphate coatings of dual acid-etched surfaces (DAEs) can improve periimplant bone regeneration. Ten adult female foxhounds received experimental titanium screw implants in the mandible 3 months after removal of all premolar teeth. Five types of surface states were evaluated in each animal: (i) implants with a machined surface (MS) (Control 1); (ii) implants with a DAE (Control 2); (iii) implants with a DAE coated with collagen I (Control 3); (iv) implants with a DAE with mineralized collagen I; and (v) implants with a DAE with a hydroxylapatite (HA) coating. Periimplant bone regeneration was assessed by histomorphometry after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the volume density of the newly formed periimplant bone (BVD). After 1 month, mean BIC of experimental implants did not differ significantly from implants with DAE and collagen-coated surfaces, but was significantly higher than the MS implants. BVD was enhanced significantly only in implants with mineralized collagen coating compared with DAE and collagen-coated controls. After 3 months, the mean values of BIC had increased significantly in the group of implants with HA and mineralized collagen coating but were not significantly different from implants with DAE and collagen-coated surfaces. The same held true for the mean BVD values. In conclusion, the present study could not verify the hypothesis that calcium phosphate coatings of DAEs in the present form enhanced periimplant bone formation compared with the DAE surface alone.

Aim: The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) enhances bone formation in sinus floor augmentations in miniature pigs. Material and methods: The maxillary sinus floors in 12 adult female Goettingen minipigs were augmented with β-tricalcium phosphate (β-TCP) on one side. The contralateral test side was augmented using two concentrations of rhGDF-5 (400 μg rhGDF-5/g β-TCP; 800 μg rhGDF-5/g β-TCP) delivered on β-TCP (six animals each). One dental implant was inserted into each sinus floor augmentation. After 4 and 12 weeks, histological and histomorphometric assessment of non-decalcified histological specimens was performed. Results: The results showed significantly higher mean values of volume density (VD) of newly formed bone using the concentration of 400 μg/g β-TCP (22.8%) compared with the respective control (8%) after 4 weeks (P=0.05). The bone-to-implant contact rates were also significantly enhanced after 4 weeks between test sites (400 μg: 41.9%; 800 μg: 40.6%) and control sites (400 μg: 7.8%; 800 μg: 16.4%) (400 μg: P=0.024; 800 μg: P=0.048). Conclusion: It is concluded that rhGDF-5 delivered on β-TCP significantly enhanced early bone formation compared with β-TCP alone in sinus lift procedures in miniature pigs.

The aim of the present study was to test the hypothesis that human recombinant bone morphogenic protein 2 (rhBMP-2) implanted in a slow release carrier of polylactic acid (PLA) can repair a non-healing defect in the rat mandible and maintain the thickness of an augmented volume. p-DL-lactic acid discs were produced and loaded with 48 and 96 microg rhBMP-2 and inserted into non-healing defects of the mandible of 45 Wistar rats. Fifteen rats received implants with 96 microg rhBMP-2 (Group 2), 48 microg rhBMP-2 (Group 1) and blank implants without BMP (Group 0) each on one side of the mandible. Unfilled defects of the same size on the contralateral sides of the mandibles served as empty controls. After 6, 13 and 26 weeks, implants of each group were retrieved from five animals each and submitted to flat panel detector computed tomography. Bone formation and thickness of augmentation was assessed by computer-assisted histomorphometry. In Group 2 significantly more bone was produced than in Group 1. Implants of Group 1 induced significantly more bone than the blank controls only after 6 weeks, whereas the difference was not significant after 13 and 26 weeks. Differences between Group 2 and Group 1 were clearly significant after 26 weeks. The thickness of bone tissue was maintained in Group 2 whereas it decreased in Group 1 and was negligible in Group 0. It is concluded that the PLA implants with 96 microg rhBMP-2 were able to bridge a non-healing defect in the rat mandible and maintained the thickness of an augmented volume. However, continuous supply of osteogenic signals appears to be required to compensate for adverse effects during polymer degradation.

Orthognathic surgery has always been a classical focus of maxillofacial surgery. Since more than 100 years, various surgical techniques for mandibular repositioning have been developed and clinically tested. Since the establishment of plate and screw osteosynthesis, orthognathic surgery became more stable and safe. Nowadays, different surgical methods for mobilising the mandible are existing. This international multicenter analysis (n = 51 hospitals) is providing first evidence based data for the current use of different surgical methods. The dominating techniques were Obwegeser/dal Pont (61%) followed by Hunsuck/Epker (37%) and Perthes/Schlössmann (29%). The main osteosynthesis materials were plates (82%), bicortical screws (23.5%), or a combination of both (5.9%). 47% of all centers reported to use several surgical methods at the same time, depending on the anatomical problem and the surgeon's preference. This shows that different surgical methods seem to work as comparable, safe, and reliable procedures in everydays clinical practise. On this basis, further prospective studies could evaluate possible advantages for our patients.

Most parents are emotionally traumatized when confronted by the birth of a baby with an orofacial cleft (OFC). Affected families may have to compensate for increased financial, social and personal impacts before primary treatment is completed. This study was conducted to identify factors influencing the quality of life (QoL) of families having young children with OFC. A self-administered questionnaire containing the impact on family scale was applied in 130 consecutive families having children with OFC aged between 6 and 24 months. The results were related to the type of cleft and the time of initial diagnosis using non-parametric tests and multivariate correlation analysis (P < 0.05). In families having children with isolated cleft lip, financial and social impacts were reduced, but problems in coping were increased when compared to families with children having cleft lip and palate or isolated cleft palate. Total impact was highest in families having children with isolated cleft palate, probably due to later surgery for reconstruction. Prenatal diagnosis of OFC did not reduce the general impact on affected families, but increased the social impact. The relation of certain impacts to distinct types of cleft might allow more tailored support of affected families and improve their QoL.

The assignment for this working group was to update the existing knowledge regarding factors considered being of special relevance for the patient undergoing implant therapy. This included areas where conflicting opinions exists since long or recently has been expressed, like the role of antibiotic prophylaxis in dental implant surgery and peri-implantitis. Also areas with growing interest and concern such as patient-reported outcome measures (PROMs) and health-economy was included in this review.The literature in the respective areas of interest (antibiotic prophylaxis, peri-implantitis, patient-reported outcome measurements and health-economic aspects) was searched using different strategies for the different papers. Search strategies ranged from a complex systematic review to systematic- and narrative reviews, depending on subject and available literature. All collected material was critically reviewed. Four manuscripts were subsequently presented for group analysis and discussion and plenum discussions and concensus approval. The selected areas were considered to be of key importance and relevance for the patient undergoing implant therapy.The results and conclusions of the review process are presented in the respective papers. The group's conclusions, identified knowledge gaps, directions for future research and concensus statements are presented in this article. The following reviews were available for group discussions and the foundation for subsequent plenary sessions: Lund B, Hultin M, Tranaeus S, Naimi-Akbar A, Klinge B. (2015) Perioperative antibiotics in conjunction with dental implant placement. A complex systematic review. Renvert SQuirynen M. (2015) Risk indicators for peri-implantitis. A narrative review. De Bruyn H, Raes S, Matthys C, Cosyn J. (2015) The current use of patient centered/reported outcomes in implant dentistry. A systematic review. Beikler TFlemmig T.F. (2015) Economic evaluation of implant-supported prostheses. A narrative review.