Currently, maxillary sinus floor (SF) elevation is based on off-the-shelf allogeneic, xenogeneic or synthetic bone augmentation materials (BAM) that are implanted via an open lateral sinus wall approach (OSFE). However, this invasive method is associated with postoperative complications caused by an inadequate blood supply of the alveolar ridge. Balloon-assisted procedures are minimal invasive alternatives with lower complication rates. The aim was to evaluate local new bone (NB) formation in the SF following the application of a particulate BAM (Easy graft) via two different SF elevation techniques in a split mouth mini-pig sinus augmentation model. Seven adult Goettingen minipigs were used for evaluation of a biphasic ceramic (PLGA/ß-TCP) BAM in the elevated SF region. Treatments were randomized to the contralateral sinus sites and included two procedures: OSFE (control group) versus minimally invasive SF elevation by a balloon-lift-control system (BLC) (treatment group). The animals were euthanized after 28 and 56 days for analysis of new bone (NB) formation. The biphasic synthetic BAM implanted via BLC increased more NB formation (5.2 ± 1.9 mm and 4.9 ± 1.6 mm vs. 2.6 ± 0.5 mm) and osseointegration of the particles (18.0 ± 6.0

Background Osteosarcomas are the most common primary bone tumor while occurrence in the craniofacial skeleton is relatively rare. There are clinical differences of osteosarcomas regarding their location. In this regard craniofacial osteosarcomas (COS) have special characteristics. Extracranial osteosarcomas (EOS) occur mainly in the long bones of the extremities (tibia, humerus and femur). These tumors metastasize hematogenically at a very early stage. In comparison, COS are mainly localized in the mandible and maxilla, occur later in life and show significantly less and later metastasis and respond differently to adjuvant therapy. In the literature, clinical characteristics of COS and EOS are rarely compared directly. The aim of this systematic review is to answer the question whether COS and EOS exhibit fundamentally different clinical behavior and how they differ in terms of survival rates and response to different therapies. Methods A systemic review was performed. Pubmed, Cochrane and Google Scholar were used as search engines. The literature research was done by using clearly defined terms and their links. 124 full texts were selected and evaluated for this review. The inclusion criteria were determined using the PICO model. Results COS have significantly better survival rates, especially if they are located in the jawbone. Surgical R0 resection is crucial for therapeutic success. The study situation regarding the benefit of neoadjuvant chemotherapy in COS is very inhomogeneous. There is also no evidence for the benefit of adjuvant radio- or chemotherapy in COS. The large heterogeneity of the studies in terms of therapeutic concept, initial situation of the patients and outcome considered, as well as the small number of patients with craniofacial osteosarcoma were limiting factors. Conclusion The results of this study show the clear therapeutic and prognostic differences between COS and EOS and underline the necessity to consider both types of osteosarcoma as independent tumor entities in future studies. Furthermore, the study highlights the importance of surgical R0 resection for the prognosis of COS patients. There is no evidence for therapeutic benefit of adjuvant/neoadjuvant radio-/chemotherapy in R0 resected COS cases.

Head and neck cancer (HNC) and its treatment can lead to various functional impairments. We developed and validated an instrument for rapid physician-rated assessment of basic functional outcomes in HNC patients. HNC-relevant functional domains were identified through a literature review and assigned to verbal ratings based on observable criteria. The instrument draft was subjected to systematic expert review to assess its face and content validity. Finally, the empirical validity, reliability, and responsiveness of the expert-adapted Functional Integrity in Head and Neck Cancer (HNC-FIT) scales were assessed in healthy controls and in HNC patients. A matrix of the 6 functional domains of oral food intake, respiration, speech, pain, mood, and neck and shoulder mobility was created, each with 5 verbal rating levels. Face and content validity levels of the HNC-FIT scales were judged to be adequate by 17 experts. In 37 control subjects, 24 patients with HNC before treatment, and in 60 HNC patients after treatment, the HNC-FIT ratings in the 3 groups behaved as expected and functional domains correlated closely with the outcome of corresponding scales of the EORTC-HN35-QoL questionnaire, indicating good construct and criterion validity. Interrater reliability (rICC) was ≥0.9 for all functional domains and retest reliability (rICC) was ≥0.93 for all domains except mood (rICC = 0.71). The treatment effect size (eta-square) as a measure of responsiveness was ≥0.15 (p < 0.01) for fall domains except for breathing and neck and shoulder mobility. The median HNC-FIT scale completion time was 1 min 17 s. The HNC-FIT scale is a rapid tool for physician-rated assessment of functional outcomes in HNC patients with good validity, reliability, and responsiveness.

In the pedigree, one of the individuals was marked as unaffected whereas it is heterozygous for the SLC24A4 mutation.

In the pedigree, one of the individuals was marked as unaffected whereas it is heterozygous for the SLC24A4 mutation.

Background: Due to aging, tissue regeneration gradually declines. Contemporary strategies to promote tissue-specific regeneration, in particular in elderly patients, often include synthetic material apt for implantation primarily aiming at upholding body functions and regaining appropriate anatomical and functional integrity. Objective: Biomaterials suitable for complex reconstruction surgical procedures have to exert high physicochemical stability and biocompatibility. Method: A polymer made of poly-L-lactic acid and poly-ε-caprolactone was synthesized by means of a novel tin-free catalytic process. The material was tested in a bioreactor-assisted perfusion culture and implanted in a sheep model for lateral augmentation of the mandible. Histological and volumetric evaluation was performed 3 and 6 months post-implantation. Results: After synthesis the material could be further refined by cryogrinding and sintering, thus yielding differently porous scaffolds that exhibited a firm and stable appearance. In perfusion culture, no disintegration was observed for extended periods of up to 7 weeks, while mesenchymal stromal cells readily attached to the material, steadily proliferated, and deposited extracellular calcium. The material was tested in vivo together with autologous bone marrow-derived stromal cells. Up to 6 months post-implantation, the material hardly changed in shape with composition also refraining from foreign body reactions. Conclusion: Given the long-term shape stability in vivo, featuring imperceptible degradation and little scarring as well as exerting good compatibility to cells and surrounding tissues, this novel biomaterial is suitable as a space filler in large anatomical defects.

Objective: To estimate whether outcomes at 12-month follow-up may be predicted by an intermediate and early response to a 3 mm resilient splint therapy for unilateral arthralgia and myofascial pain assessed at 3- and 6-month follow-ups.Methods: Data obtained from one retrospective cohort study consisting of 78 patients suffering from chronic and sub-acute unilateral arthralgia and myofascial pain who were managed with 3 mm resilient splint therapy were subjected to analysis.Results: Baseline visual analog scale (VAS) intensity, gender as well as changes in the intensity of VAS pain at 3- and 6-month follow-ups predicted unilateral arthralgia and myofascial pain group membership (p < .001). The function classified 83.3% of the cross-validated and 87.2% of original grouped cases correctly.Discussion: The proposed model may be used to timely identify patients who are at risk of developing prolonged non-responsive unilateral arthralgia and myofascial pain chronicity.

By coating surfaces with nano-crystalline diamond (NCD) particles, hydrophilicity can be altered via sidechain modifications without affecting surface texture. The present study aimed to assess the impact of NCD hydrophilicity on machined and rough SLA titanium discs on soft tissue integration, using a rodent model simulating submerged healing. Four different titanium discs (machined titanium = M Titanium, NCD-coated hydrophilic machined titanium = M-O-NCD, sand blasted acid etched (SLA Titanium) titanium, and hydrophilic NCD-coated SLA titanium = SLA O-NCD) were inserted in subdermal pockets of 12 Wistar rats. After one and four weeks of healing, the animals were sacrificed. Biopsies were embedded in methyl methacrylate (MMA), and processed for histology. The number of cells located within a region of interest (ROI) of 10 µm around the discs were counted and compared statistically. Signs of inflammation were evaluated descriptively employing immunohistochemistry. At one week, M-O-NCD coated titanium discs showed significantly higher amounts of cells compared to M Titanium, SLA Titanium, and SLA-O-NCD (p < 0.001). At four weeks, significant higher cell counts were noted at SLA-O-NCD surfaces (p < 0.01). Immunohistochemistry revealed decreased inflammatory responses at hydrophilic surfaces. Within the limits of an animal study, M-O-NCD surfaces seem to stimulate cell proliferation in the initial healing phase, whereas SLA-O-NCD surfaces appeared advantageous afterwards.

Biofunctionalization of scaffold materials can enable the healing of large bone defects. In case of minimally invasive guided-bone regeneration (GBR), limitations are however hard-to-control side effects related to the potential release of biofactors into the systemic environment. Biofactors can be stably bound to nanodiamond particles (ND) through physisorption. We therefore tested the biological and clinical effects of refining beta-tricalcium phosphate (βTCP) with ND in vitro and in vivo. In vitro, βTCP carrying 4% ND resulted in enhanced attachment of mesenchymal stem cells. When assessing GBR after lateral augmentation of the mandible in sheep showed that ND in βTCP resulted in a consistently steady bone formation when compared to pure βTCP, demonstrating the biological inert behavior and the potential clinical safety of ND.

Biodegradable β-TCP implant materials functionalized with diamond nanoparticles are generated and characterized.

Background. Radiation therapy (RT) of the head and neck region is often accompanied by serious side effects. Research in this area is needed to improve treatment outcomes and ameliorate therapy tolerance. Laboratory rodents are barely matching today's clinical standards in RT research. Yet domestic swine (Sus scrofa domestica) have previously proved suitable for various advanced tests in clinical research and training. We therefore investigated whether S. scrofa domestica is also appropriate for irradiation of the mandible.Study Design. A common scheme for irradiation treatment of S. scrofa domestica mandibles in a split-mouth design was acquired by applying computed tomography (CT) scanning under sedation. Basing on close anatomic resemblance, a standard treatment plan comprising 2 opposed irradiation fields could be accomplished.Results. RT was carried out in a clinical environment with 2 x 9 Gy. The resulting operating procedure facilitated complication-free sedation, transport, positioning, CT scanning, and effective irradiation.Conclusion. Based on common standards applied for RT in humans, domestic pigs can be employed to progress RT clinical research. Due to their human-like anatomy, physiology, size, and weight, the swine model is expedient for advancing experimental RT of the head and neck area.

Purpose: The objective of this study was to assess the association between temporomandibular joint (TMJ) condylar erosion and chronic TMJ arthralgia.Materials and Methods: Based on a sample size estimation, this case-and-control study involved 198 patients 16 to 73 years old recruited from a routine clinical practice (99 cases, patients with chronic TMJ arthralgia and mean pain duration of 16.4 months; 99 controls, asymptomatic patients without a history of orofacial pain). The clinical diagnosis of arthralgia was made according to the Research Diagnostic Criteria for Temporomandibular Disorders. Cone-beam computed tomographic (CBCT) images were evaluated for the presence or absence of erosive osseous changes of the TMJ condyle. Severity of TMJ condylar erosion was classified as grade 0 (absence of erosion), grade I (slight erosion), grade II (moderate erosion), or grade III (extensive erosion). Logistic regression analysis was used to assess the association between chronic TMJ arthralgia and condylar erosion, adjusting for age, gender, number of missing posterior teeth, and number of dental quadrants with missing posterior teeth.Results: TMJ condylar erosion was found in 59.6% of cases and 21.2% of controls. There was a significant association between TMJ arthralgia and degree of condylar erosion (P<.001). The odds ratio that a TMJ with condylar erosion grade II might belong to the TMJ arthralgia group was strong (3.1:1; 95% confidence interval [CI], 1.17 to 8.09) and significant (P=.023). Significant increases in risk of TMJ arthralgia occurred with condylar erosion grade III (7.7:1; 95% CI, 3.09 to 19.18; P<.001).Conclusions: The study provides evidence of an association between TMJ condylar erosion and chronic TMJ arthralgia. (C) 2016 American Association of Oral and Maxillofacial Surgeons.

Biofunctionalized scaffold facilitates complete healing of large defects. Biological constraints are induction and ingrowth of vessels. Angiogenic growth factors such as vascular endothelial growth factor or angiopoietin-1 can be bound to nano-scaled diamond particles. Corresponding bioactivities need to be examined after biofunctionalization. We therefore determined the physisorptive capacity of distinctly manufactured, differently sized nDP and the corresponding activities of bound factors. The properties of biofunctionalized nDPs were investigated on cultivated human mesenchymal stem cells and on the developing chicken embryo chorio-allantoic membrane. Eventually porous bone substitution material was coated with nDP to generate an interface that allows biofactor physisorption. Angiopoietin-1 was applied shortly before scaffold implantation into an osseous defect in sheep calvaria. Biofunctionalized scaffolds exhibited significantly increased rates of angiogenesis already one month after implantation. Conclusively, nDP can be used to ease functionalization of synthetic biomaterials. (C) 2015 Elsevier Inc. All rights reserved.

Zellbasierte Therapien sind vielversprechende neue Methoden zur Rekonstruktion ausgeprägter Gewebedefekte. In der Mund-, Kiefer- und Gesichtschirurgie stellen vor allem knöcherne Defekte eine große Herausforderung dar. Sie werden vielfach mit autologen Transplantaten behandelt. Der Artikel gibt einen Überblick über bereits publizierte klinische Anwendungen im Bereich der präimplantologischen Augmentation, der Behandlung von Kieferspalten sowie der Rekonstruktion großer Defekte.

OBJECTIVES To investigate the impact of meta-analytic evidence in scientific literature on clinical decision making in the field of oral implantology. METHODS A Delphi opinion poll was performed at the meeting of the "Next Generation" Committees of the Austrian, German and Swiss Societies for Implantology (ÖGI, DGI and SGI). First, the experts gave their opinion on 20 questions regarding routine implant treatment (uninformed decisions), then they were confronted with up-to-date Level I evidence from scientific literature on these topics and again asked to give their opinion (informed decisions) as well as to rate the available evidence as satisfactory or insufficient. Topics involved surgical issues, such as immediate implant placement, flapless surgery, tilted and short implants and bone substitute materials, as well as opinions on prosthodontic paradigms, such as immediate loading, abutment materials and platform switching. RESULTS Compared to their uninformed decisions prior to confrontation with recent scientific literature, on average, 37% of experts (range: 15-50%) changed their opinion on the topic. When originally favoring one treatment alternative, less than half were still convinced after review of meta-analytic evidence. Discrepancy between uninformed and informed decisions was significantly associated with insufficient evidence (P = 0.014, 49% change of opinion vs. 26% on topics rated as sufficiently backed with evidence). Agreement regarding strength of evidence could be reached for eight topics (40%), in three issues toward sufficiency and in five issues toward lack of evidence. CONCLUSION Confrontation with literature results significantly changes clinical decisions of implantologists, particularly in cases of ambiguous or lacking meta-analytic evidence.

OBJECTIVES:We aimed to determine the extent of acute endothelial cell loss and neointimal proliferation in the long-term in saphenous vein grafts (SVGs) exposed to defined distension pressures.METHODS:During routine competence testing of SVGs for coronary artery bypass grafting (CABG), blinded peak pressure measurements were performed in 10 patients. In an experimental set-up, distension pressure-related endothelial damage was studied in the SVGs of 20 patients. In a subgroup (n = 10), each patient's SVG was divided into segments and subjected to four constant pressures (50, 100, 150 and 300 mmHg) for 30 min each. In another subgroup (n = 10), SVGs were exposed to a short phase of high pressure (low pressure followed by 300 mmHg for 5 min). Acute endothelial cell loss was quantified by CD31-immunostaining. After 2 weeks of organ culture, the neointimal proliferation was evaluated using histomorphometry. Pressure-related damage was compared with damage at baseline (0 mmHg).RESULTS:During routine competence testing for CABG, we revealed a median peak pressure of 355 mmHg (range: 240-639 mmHg). In the experimental set-up, significant acute endothelial cell loss occurred at all tested distension pressures: at 50 mmHg, the median endothelial cell loss was 29% (range: 20-51%, P = 0.015), at 100 mmHg 54% (range: 37-69%, P < 0.001), at 150 mmHg 75% (range: 41-88%, P < 0.001), at 300 mmHg 91% (range: 63-100%, P < 0.001) and at short high-pressure exposure 65% (range: 49-82%, P < 0.001) in comparison with 20% (range: 0-44%) at baseline. Significant neointimal proliferation occurred when a distension pressure of 50 mmHg was exceeded: at 50 mmHg, median neointimal proliferation was 97 µm (range: 60-380 µm, P = 0.176), at 100 mmHg 168 µm (range: 100-600 µm, P = 0.001), at 150 mmHg 183 µm (range: 160-440 µm, P < 0.001) at 300 mmHg 347 µm (range: 190-590 µm, P < 0.001) and at short high-pressure exposure 130 µm (range: 60-410 µm, P = 0.02) in comparison with 90 µm (range: 60-170 µm) at baseline.CONCLUSIONS:In vitro exposure of SVGs to low distension pressure ranges causes significant acute endothelial cell loss and crucial long-term damage, namely neointimal proliferation.

Craniomaxillofacial (CMF) trauma occurs in isolation or in combination with other serious injuries, including intracranial, spinal, and upper- and lower-body injuries. It is a major cause of expensive treatment and rehabilitation requirements, temporary or lifelong morbidity, and loss of human productivity. The aim of this study was to evaluate patterns of CMF trauma in a large patient sample within a 15-year time frame. Between 1991 and 2005, CMF trauma data were collected from 14,654 patients with 35,129 injuries at the Department of Cranio-Maxillofacial and Oral Surgery in Innsbruck, assessing a plethora of parameters such as injury type and mechanism as well as age and gender distribution over time. Three main groups of CMF trauma were evaluated: facial bone fractures, dentoalveolar trauma, and soft tissue injuries. Statistical comparisons were carried out using a chi-square test. This was followed by a logistic regression analysis to determine the impact of the five main causes for CMF injury. Older people were more prone to soft tissue lesions with a rising risk of 2.1% per year older, showing no significant difference between male and female patients. Younger patients were at higher risk of suffering from dentoalveolar trauma with an increase of 4.4% per year younger. This number was even higher (by 19.6%) for female patients. The risk of sustaining facial bone fractures increased each year by 4.6%. Male patients had a 66.4% times higher risk of suffering from this type of injury. In addition, 2550 patients (17.4%) suffered from 3834 concomitant injuries of other body parts. In summary, we observed changing patterns of CMF trauma over the last 15 years, paralleled by advances in refined treatment and management options for rehabilitation and reconstruction of patients suffering from CMF trauma.

OBJECTIVES Connective tissue in contact to transgingival/-dermal implants presents itself as tight scar formation. Although rough surfaces support the attachment they increase bacterial colonisation as well. In contrast to surface roughness, little is known about the influence of surface wettability on soft-tissue healing in vivo. We therefore investigated the influence of different surface wettabilities on connective tissue healing at polished implant surfaces in vivo. MATERIAL AND METHODS Three polished experimental groups (titanium, titanium coated with hydrophobic nano-crystalline diamond (H-NCD) and titanium coated with hydrophilic nano-crystalline diamond (O-NCD) were inserted into the subcutaneous connective tissue of the abdominal wall of 24 rats. Animals were sacrificed after 1 and 4 weeks resulting in eight specimen per group per time point. Specimen were subjected to histological evaluation (van Giesson's staining) and immunohistochemistry staining for proliferating cell nuclear antigen (PCNA), fibronectin and tumour necrosis factor-alpha (TNF-α). RESULTS Histological evaluation revealed dense scar formation at the titanium and H-NCD surfaces. In contrast, the connective tissue was loose at the O-NCD surface with a significantly higher number of cells after 4 weeks. O-NCD demonstrated a strong expression of PCNA and fibronectin but a weak expression of TNF-α. In contrast, the PCNA and fibronectin expression was low at the titanium and H-NCD, with a strong signal of TNF-α at the H-NCD surface. CONCLUSIONS Hydrophilicity influences the connective tissue healing at polished implant surfaces in vivo positively. The attachment of connective tissue and the number of cells in contact to the surface were increased. Moreover, the inflammatory response is decreased at the hydrophilic surface.

AIMS:Despite the lower patency of venous compared with arterial coronary artery bypass grafts, approximately 50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). METHODS AND RESULTS:We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. CONCLUSION:Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease.

Introduction Long term patency rates for coronary artery bypass grafting (CABG) using autologous saphenous vein are poor, showing 10 years post-CABG patency rates of 41%. To date, effective and proven pharmacologic interventions to prolong vein graft patency are lacking. Gene therapy seems particularly well suited for the prevention or postponement of vein graft failure since (1) the stimulation of smooth muscle cell proliferation appears to largely be an early and transient process, and (2) the target tissue is easily accessible ex vivo during the surgical procedure. However, a major obstacle in efficient gene transfer to human vein grafts is the heterogenity of vessel quality due to age, preexisting veinous disease, and surgical trauma. In this study we developed a clinically relevant viral delivery technique to achieve a reproducible and efficient gene transfer in human vein grafts. Methods 46 intact human saphenous veins (age 68+/−7) from patients undergoing coronary bypass surgery were cut into rings 15 mm in length. A small piece of each vein was tested for endothelial viability with trypan blue. Individual vein rings were endoluminally incubated with adenoviral vectors expressing two reportergenes (Ad.CMV.lacZ/GFP, 1x10E11 pfu/mL) with different intraluminal pressures (50, 100, 150mmHg) for 30 or 60 minutes. Veinsegments were cultured for 6days after transfection and harvested for cryopreservation. Transfection efficiency was evaluated by X-gal staining and GFP- Westernblot; endothelial integrity and neointima-hyperplasia were evaluated by CD31-staining, Elastica Van Gieson-staining and H-E-staining. Results Veins which underwent endoluminal gene transfer without pressure showed only poor transfection efficiency (12%+/−7). In contrast, veins wich were pressure-transfected with either 100 or 150 mmHg showed high transfection efficiency throughout the vessel wall (75%−+/−13 and 91+/−7% respectively, p<0.02). Veins transfected for 60 minutes showed no significant difference in transfection efficiency versus 30 minute incubation. However, CD31 staining revealed a significant loss of endothelium in the high pressure group (150 mmHg), whereas the 100 mmHg pressure group showed only minor endothelial damage compared to control veins, irrespective of incubation time. Discussion This study presents an optimized transfection protocol for gene transfer in human vein grafts. We here show for the first time that viral transfection using carefully regulated supraphysiological endoluminal pressure greatly enhances transfection efficiency in human veins. Using continuous intraluminal pressure-monitoring and careful evaluation of endothelial integrity, we found optimal conditions for highly efficient and reproducible transfection using 100 mmHg intraluminal pressure for 30 minutes. Establishing a safe and efficient delivery method in a clinically relevant model for human cardiovascular gene therapy is an important aspect of translation from pre-clinical to clinical gene therapy.