Background The present study evaluated the cellular tissue reaction of two equine-derived collagen hemostatic sponges (E-CHS), which differed in thickness after pressing, over 30 days in vivo. The inflammatory response during physiological wound healing in sham-operated animals was used as control group. Material and methods First, the E-CHS was pressed by applying constant pressure (6.47 ± 0.85 N) for 2 min using a sterile stainless-steel cylinder until the material was uniformly flattened. Consequently, the original (E-CHS), the pressed (P-E-CHS), as well as the control group (CG; sham operation) were studied independently. The 3 groups were evaluated in vivo after subcutaneous implantation in Wistar rats during 3, 15, and 30 days. Histochemical and immunohistochemical methods provided observations of biomaterial degradation rate, cellular inflammatory response, and vascularization pattern. A derivative of human blood known as platelet-rich fibrin (PRF) was used as an ex vivo model to simulate the initial biomaterial-cell interaction. Segments of E-CHS and P-E-CHS were cultivated for 3 and 6 days with PRF, and the release of pro-inflammatory proteins was measured using ELISA. PRF cultivated alone was used as a control group. Results At day 3, the CG induced a statistically significant higher presence of monocytes/macrophages (CD68+), pro-inflammatory macrophages (M1; CCR7+), and pro-wound healing macrophages (M2; CD206+) compared to E-CHS and P-E-CHS. At the same time point, P-E-CHS induced a statistically significant higher presence of CD68+ cells compared to E-CHS. After 15 days, E-CHS was invaded by cells and vessels and showed a faster disintegration rate compared to P-E-CHS. On the contrary, cells and vessels were located only in the outer region of P-E-CHS and the biomaterial did not lose its structure and accordingly did not undergo disintegration. The experimental groups induced similar inflammatory reaction primarily with positive pro-inflammatory CD68+/CCR7+ macrophages and a low presence of multinucleated giant cells (MNGCs). At this time point, significantly lower CD68+/CCR7+ macrophages and no MNGCs were detected within the CG when compared to the experimental groups ( P < 0.05). After 30 days, E-CHS and P-E-CHS were fully degraded. All groups showed similar inflammatory reaction shifted to a higher presence CD206+ macrophages. A low number of CCR7+ MNGCs were still observable in the implantation bed of both experimental groups. In the ex vivo model, the cells and fibrin from PRF penetrated E-CHS. However, in the case of P-E-CHS, the cells and fibrin stayed on the surface and did not penetrate towards materials central regions. The cultivation of P-E-CHS with PRF induced a statically significant higher release of pro-inflammatory proteins compared to the CG and E-CHS after 3 days. Conclusion Altering the original presentation of a hemostatic sponge biomaterial by pressing modified the initial biomaterial-cell interaction, delayed the early biomaterial’s degradation rate, and altered the vascularization pattern. A pressed biomaterial seems to induce a higher inflammatory reaction at early time points. However, altering the biomaterial did not modify the polarization pattern of macrophages compared to physiologic wound healing. The ex vivo model using PRF was shown to be an effective model to simulate the initial biomaterial-cell interaction in vivo. Clinical relevance A pressed hemostatic sponge could be applied for guided tissue regeneration and guided bone regeneration. In that sense, within the limitations of this study, the results show that the same biomaterial may have two specific clinical indications.

Das Plattenepithelkarzinom stellt das sechsthäufigste Malignom des Menschen weltweit dar. Aufgrund der anatomischen Lokalisation im sichtbaren Bereich und seiner engen Lagebeziehung zu wichtigen funktionellen und ästhetischen Strukturen hat dieser bösartige Tumor erhebliche Folgen auf die Lebensqualität der Betroffenen. Daher ist eine hohe Präzision in Hinblick auf Diagnostik und Therapie erforderlich, v. a. um die Funktion zu erhalten. Die Diagnostik und Therapie der Tumorpatienten sind eine interdisziplinäre Aufgabe. Dieser Beitrag gibt einen Überblick über die wichtigsten Punkte im Bereich der Diagnostik und Vorbereitung der Therapie des oralen Plattenepithelkarzinoms. Dabei wird insbesondere die Zusammenarbeit zwischen Zahnarzt, Hausarzt, MKG-Chirurgen, Strahlentherapeuten, Onkologen und betreuendem Psychoonkologen hervorgehoben.

To compare dynamic magnetic resonance imaging (MRI) with videofluoroscopy (VFS) regarding image quality and assessment of gap size between soft palate (SP) and posterior pharyngeal wall (PPW) in children and adolescents following surgical correction of velopharyngeal dysfunction (VPD). Twenty-one patients undergoing unenhanced 3-T MRI and contrast-enhanced VFS were included in this IRB-approved prospective study. The MRI scan protocol comprised refocused gradient-echo sequences in transverse and sagittal planes during speech, with TE 1.97 ms, TR 3.95 ms, flip angle 8°, matrix size 128 × 128, and 5-mm slice thickness. Radial k-space sampling and sliding window reconstruction were used to achieve an image acquisition rate of 28 frames per second (fps). VFS with 30 fps was similarly performed in both planes. Closure of the velopharyngeal port during phonation was evaluated by two experienced radiologists. Eleven (52.4%) patients displayed a complete closure, whereas ten (47.6%) patients showed a post-operative gap during speech. VFS and MRI equally identified the cases with persistent or recurrent VPD. Differences in SP-PPW distance between VFS (3.9 ± 1.6 mm) and MRI (4.1 ± 1.5 mm) were not statistically significant (p = 0.5). The subjective overall image quality of MRI was rated inferior (p < 0.001) compared with VFS, with almost perfect inter-rater agreement (κ = 0.90). The presence of susceptibility artifacts did not limit anatomical measurements. Dynamic MRI is equally reliable as VFS to assess persistent or recurrent inadequate velum closure in patients following surgical treatment of VPD. • Unenhanced 3-T dynamic MRI and contrast-enhanced videofluoroscopy are equally useful for the identification of patients with incomplete velopharyngeal closure during speech. • MRI using refocused gradient-echo acquisition with radial k-space sampling and sliding window reconstruction generates diagnostic images with 28 frames per second. • MRI can offer a radiation-free alternative to currently established videofluoroscopy for young patients.

Squamous cell carcinoma is the sixth most common malignancy worldwide. The anatomic location of this malignant tumor in the visible region and its proximity to important functional and aesthetic structures of the head and neck have considerable consequences for the quality of life and psychosocial situation of the patients. Therefore, high precision is required for diagnosis and treatment, particularly to preserve function. Diagnosis and treatment of cancer patients are interdisciplinary tasks. The current article highlights the most important aspects pertaining to diagnosis and treatment of oral squamous cell carcinoma, with particular focus on the collaboration between general practitioners, dentists, oral and maxillofacial surgeons, oncologists, radiation therapists, and psycho-oncologists.

Purpose The present study evaluated the platelet distribution pattern and growth factor release (VEGF, TGF-β1 and EGF) within three PRF (platelet-rich-fibrin) matrices (PRF, A-PRF and A-PRF+) that were prepared using different relative centrifugation forces (RCF) and centrifugation times. Materials and methods immunohistochemistry was conducted to assess the platelet distribution pattern within three PRF matrices. The growth factor release was measured over 10 days using ELISA. Results The VEGF protein content showed the highest release on day 7; A-PRF+ showed a significantly higher rate than A-PRF and PRF. The accumulated release on day 10 was significantly higher in A-PRF+ compared with A-PRF and PRF. TGF-β1 release in A-PRF and A-PRF+ showed significantly higher values on days 7 and 10 compared with PRF. EGF release revealed a maximum at 24 h in all groups. Toward the end of the study, A-PRF+ demonstrated significantly higher EGF release than PRF. The accumulated growth factor releases of TGF-β1 and EGF on day 10 were significantly higher in A-PRF+ and A-PRF than in PRF. Moreover, platelets were located homogenously throughout the matrix in the A-PRF and A-PRF+ groups, whereas platelets in PRF were primarily observed within the lower portion. ​Discussion the present results show an increase growthfactor release by decreased RCF. However, further studies must be conducted to examine the extent to which enhancing the amount and the rate of released growth factors influence wound healing and biomaterial-based tissue regeneration. ​Conclusion These outcomes accentuate the fact that with a reduction of RCF according to the previously LSCC (described low speed centrifugation concept), growth factor release can be increased in leukocytes and platelets within the solid PRF matrices.

Introduction: Cutaneous defects that occur after skin cancer resection are conventionally reconstructed by skin transplantation.This procedure is accompanied by a high morbidity, extensive operation time and postoperative pain.After preclinical evaluation and intraoral application of a three-dimensional collagen-based matrix (CM), the aim of this case series was to investigate the cutaneous regeneration by means of this collagen-based matrix after cancer resection of Basal Cell Carcinoma and malignant melanoma without skin transplantation.

Different tissue engineering techniques are used to support rapid vascularisation.A novel technique is the use of platelet-rich fibrin (PRF), an autologous source of growth factors.This study was the first to investigate the influence of PRF matrices, isolated following different centrifugation protocols, on human dermal vascular endothelial cells (ECs) in mono-culture and co-culture with human primary fibroblasts (HFs) as an in vitro model for tissue regeneration.Focus was placed on vascular structure formation and growth factor release.HFs and ECs were cultivated with PRF prepared using a high (710 ×g) or low (44 ×g) relative centrifugation force (RCF) over 14 d.Immunofluorescence staining and immunohistochemistry were used to evaluate the microvascular formation.Cell culture supernatants were collected for evaluation of growth factor release.The results showed a PRF-mediated effect on the induction of angiogenesis in ECs.Microvessel-like structure formation was promoted when ECs were combined with low-RCF PRF as compared to high-RCF PRF or control group.The percentage of vascular lumen area was significantly higher in low-RCF PRF, especially at day 7, which coincided with statistically significantly higher growth factor [vascular endothelial factor (VEGF), transforming growth factor β1 (TGF-β1) and platelet derived growth factor (PDGF)] concentration measured in low-RCF PRF as compared to high-RCF PRF or control group.In conclusion, reducing the RCF according to the low-speed centrifugation concept (LSCC) resulted in increased growth factor release and angiogenic structure formation with EC mono-culture, suggesting that PRF may be a highly beneficial therapeutic tool for tissue engineering applications.

Zahlreiche Studien belegen, dass alloplastische Kiefergelenkendoprothesen verglichen mit autologem Kiefergelenkersatz effizienter für die Wiederherstellung der normalen Anatomie und Funktion des Kiefergelenks und der vertikalen Kieferrelation sind. Die Verwendung alloplastischer Materialien für Kiefergelenkendoprothesen vermeidet die Entnahmemorbidität, ermöglicht die sofortige oder zumindest frühzeitige Einleitung der postoperativen Rehabilitation, verringert die Operationszeit und die Wahrscheinlichkeit einer Reankylose. Allerdings unterliegen alle alloplastischen Materialien der Materialermüdung, d. h. die andauernde Bewegung erzeugt Abrieb. Unabhängig von den implantierten Biomaterialien kann sich eine Fremdkörperreaktion entwickeln. Titan oder Titanlegierungen in Kombination mit ultrahochmolekularem Polyethylen (UHMWPE) haben eine minimale Sensibilisierungsrate. Die Nachsorgeergebnisse über 15 Jahre mit UHMWPE-Titan-Prothesen der jüngeren Generation zeigen eine hohe Zuverlässigkeit.

Head and neck cancer patients are at high risk of getting an oropharyngeal dysphagia following surgical therapy. Early identification of oropharyngeal dysphagia can improve outcomes and decrease economic burden. The presented results on the one hand aims to examine the validity of a water screening test with progressing volumes in postsurgical head and neck cancer patients for the early identification. On the other hand, the impact of the used surgical reconstruction concept after ablative tumour surgery should be proven. Swallowing diagnostics concerning the danger of oropharyngeal dysphagia were performed by using a water screening test combined with further instrumental diagnostics: aspiration and limitations in oral intake was investigated by fibreoptic endoscopic evaluation of swallowing by the technique of Susan Langmore called FEES. Oropharyngeal dysphagia was postoperatively detected by FEES in 65%, with aspiration in 49%, silent in 21% and limitations in oral intake in 56%. Despite a good sensitivity (aspiration = 100%; limitations in oral intake = 97.8%) the presented water-screening test did not satisfactorily predict both these reference criteria due to low positive likelihood ratio (aspiration = 2.6; limitations in oral intake = 3.1). However, it was an accurate tool for the early identification of ODG (sensitivity = 96.2; positive likelihood ratio = 5.4) in postsurgical head and neck cancer patients. On the other hand, our results show a clear demand for functional reconstruction after surgical tumour ablation. As main important factors to reduce incidence of postoperative oropharyngeal dysphagia, immediate reconstruction of a (partially) resected mandible and the reconstruction or preservation of the tip of the tongue were shown.

Background: Despite significant improvements in functional speech rehabilitation of patients with cleft palate during the past decades, speech-supporting surgery belongs to the standard repertoire of secondary cleft surgery. However, there are few objective comparisons between the various surgical techniques regarding indication, predictability of the functional speech outcome and the real outcome. Methods: From 2006 to 2011, speech-assisted surgery was performed in 40 patients with velopharyngeal insufficiency. These patients had the following diagnoses: 17 unilateral total cleft lip and palate, 10 isolated cleft palate and 13 syndromal submucosal clefts with 22q11 deletion syndrome. Indication and selection of the surgical technique were performed by logopedic-perceptive examination and imaging diagnostics (nasopharyngoscopy, videofluoroscopy) depending on mobility of the lateral pharyngeal walls (velopharyngoplasty [VPP] n = 17, levatorplasty n = 13). Of these 40 patients, 30 patients could be examined at least one year after operation. Out of the 10 non-examined patients six could be contacted and were satisfied, but could not take part in the survey because of time problems and two have moved overseas, so that the negative selection was only two patients (5%). All investigated patients underwent a clinical examination with standardised evaluation of speech function (GOS.SP.ASS according to Sell et al., 1994), a nasopharyngoscopy, a videofluoroscopy and a real-time MRI during speech. Results: In all 30 patients, a significant postoperative improvement of speech could be achieved, with no difference in the extent of improvement regarding the diagnosis (complete cleft lip and palate versus palatal cleft, nonsyndromic versus syndromic cleft) or selected surgical technique (VPP versus LVP). However, it was highly significant that LVP significantly improved the velar mobility compared to VPP. In 10 patients (33.3%), the postoperative result was so good that no further logopedic treatment was necessary. In another 10 patients (33.3%) there was still speech therapy performed but was going to be completed. The last third of the patient was improved, but still in treatment. In three of these patients (10%) after VPP, a secondary correction of the velopharyngeal flap was recommended for further optimisation and in seven patients (23.3%) it was recommended to perform additionally the other speech-assisted surgery. Only in one patient (3.3%) the velopharyngeal insufficiency could not be improved satisfyingly. Conclusion: The presented study shows that exact and interdisciplinary preoperative diagnostics are necessary for an exact analysis of the velopharyngeal problem, for setting up the correct indication and for the selection of the right surgical technique. In this way, a very good improvement could be achieved in almost all cases and even a normalisation of velopharyngeal function in two thirds of the patients. Interestingly, the velopharyngeal problem was found to be so complex in nearly a quarter of the patients that the indication had to be made for a combination of two different speech-assisted surgical techniques.

Medical treatment is nowadays substantially based on physical parameters like unhindered “operability” of the single individual. There is no space for biopsychosocial and other individual-related factors that also have an influence on the treatment result. Especially for patients with cleft lip and palate, this is of high evidence. Most of the physical deficits of so handicapped patients have a strong influence on the life of the individual and the families. Over all the stages of the different operations with the concomitant fears, a network of severe problems emerges which influences the whole live. And this takes place especially in a human community where a clean, immaculate and aesthetically appealing appearance is of highest value. Even if the process of the medical treatment is optimal, the burden during childhood leaves clear marks. Often the psychosocial relationships in between the family members and to the outside world are heavily incriminated. These burdens can influence the whole biography of the affected person sustainably. The presented discussion will set nearer these existential aspects of human beings and will clarify that biopsychosocial factors have to be accepted generally and equally especially compared with the classical and conservative medical treatment planning. Therefore, one future goal should be to bring back aspects of humanity to medicine. The presented lecture will show by evident examples that just for the surgery of the cleft patient's face, the success will be decisively based not only on the achieved superficial aesthetics but also on the psychological function, which is hidden behind and beyond the face.

Oral rehabilitation with dental implants nowadays seems to be a clinical routine technique. But still there are lots of patients who cannot be treated by simple implant insertion but need further surgical procedures to guarantee a sufficient dental rehabilitation like bone or soft tissue augmentation. To avoid large surgical approaches, innovative biomedical technologies can be used more and more. As one of the future technologies of the 21st century the symbiosis of material sciences, biologicals and computer technology will revolutionise reconstructive dentistry. The large economic growth in this field is attributed to the use of image-guided technologies. Especially regarding the process of excess of age in the western world, especially in compromised patients with medical risk factors the physiological healing process is disturbed, alloplastic augmentation with bone substitutes still offers problems and can show insufficient results. Based on 15 years of clinical and experimental experience it shall be shown that future problem solutions in augmentation with bone substitutes will be based on a successful inter-linkage of different areas: for this, (1) bionic biomaterials imitating natural morphology and biomechanical qualities have to be developed; (2) these materials have to be combined with biological-active factors to support and stimulate the human biosystem by osteoinductive proteins or autologous stem cells coming for instance from bone marrow aspirate; and (3) by image-based bone analysis and computer-aided augmentation techniques the micro- and macrostructure of scaffolds have to be calculated in respect to computer-aided tissue-engineering. Altogether, this can be completely related to the sense of a new system-biological approach in bony augmentation.

Kraniomandibuläre Dysfunktionen (CMD) betreffen einen erheblichen Teil der Bevölkerung. In den letzten Jahrzehnten haben computerassistierte Methoden für die Diagnostik und Therapieplanung zunehmend Eingang in die klinische Praxis gefunden.

Background: Resection of cancerous lesions of the skin cause defects of varying diameters. The transplantation of autologous grafts for covering such cutaneous defects comes along with disadvantages like a second surgical site and the risk of donor site morbidity.

Background: The physico-chemical characteristics and processing techniques of bone substitute materials (BSM) are from high relevance to clinicians and scientists as they determine the cellular reactions and the clinical success of the augmentation procedure.

Background: Speech supporting surgery (SSS) belong to the standard repertoire of cleft surgery. However, there are few objectives about different surgical techniques with respect to indication, outcome predictability and clinical results.

Background: Collagen membranes (CMs) are widely used in oral and maxillofacial surgery to enable guided tissue regeneration (GTR).

This study is the first to show the effect of vismodegib on healthy and tumour cells. Such results are vey important when considering the resection margin after tumour resection. Vismodegib is a small-molecule inhibitor of the Hedgehog signalling pathway. During embryogenesis this pathway plays an important role in the growth and development of tissues. Normally, the Hedgehog pathway is quiescent in adults. Reactivation of the Hedgehog pathway has been implicated in several cancers. In 2012, vismodegib was approved as oral medication for adults with metastatic or locally advanced basal cell carcinoma – the most common skin cancer in human. Hedgehog promotes synergistic effects guiding angiogenesis and osteogenesis. Our goals are clinically driven and we work together with industry. Aim – Establishing a “disease-in-a-dish” model for Head and Neck cancers, to study the effects of vismodegib treatment for guided tissue regeneration. The effect of vismodegib on healthy cells representing the hard- and soft-tissue, as compared to tumour cells, is investigated. The cultivation of these human cells on a biomaterial renders tissue-like constructs and allows analysing the effect of vismodegib in vitro. This unique concept is an unparalleled tool to test vismodegib. Bio-Gide® (Geistlich, Switzerland), a biocompatible, sterile resorbable bilayer collagen membrane for Guided Tissue Regeneration, is a biomaterial possessing good tissue compatibility and cell occlusivity. Cell seeding on the biomaterial and subsequent in vitro assays for growth, viability/apoptosis, adhesion, migration and gene expression were carried out. The preliminary data show that human tumour cells are elongated and interconnected by their protrusions. After three days of treatment with vismodegib, the cells were round-shaped and there was no interconnection. A high dose of vismodegib treatment did not seem to statistically significantly affect the number of living cultured tumour cells. There seemed to be a dose-dependent inhibition of proliferation by vismodegib. Gene expression analysis and relative quantification showed that vismodegib treatment weakly up-regulates hedgehog- signalling in healthy cells, but strongly down-regulates Hedgehog-signalling in tumour cells. This study has an informative character and shows how vismodegib affects proliferation as well as function of specific healthy- and tumour cell types involved in angiogenesis, osteogenesis and cancer.

INTRODUCTION:The load-carrying behavior of the human mandible can be described using finite element simulation, enabling investigations about physiological and pathological skeletal adaption. "Anatomical simulation" implies a stepwise approximation towards the anatomical reality.METHOD:The project is structured in three steps. In Step 1, the preprocessing, the simulation model is provided. Step 2 is the numerical computation. Step 3 is dedicated to the interpretation of the results. The requirements of the preprocessing are: a) realization of the organ's individual anatomy, namely its outer shape; b) the tissue's elastic properties, thus its inner consistency; and c) the organ's mechanical loads. For physiological mandibular loading, these are due to muscles, temporomandibular joints, and tooth forces. Meanwhile, the reconstruction of the macroscopic anatomy from computed tomography data is standard. The periodontal ligament is inserted ex post using an approach developed by the authors. The bone is modeled anisotropically and inhomogeneously. By the visualization of the individual fiber course, the muscular force vectors are realized. The mandibular condyle is freely mobile in a kind of simplified joint capsule. For the realization of bite forces, several approaches are available.RESULTS:An extendible software tool is provided, enabling the user - by variable input of muscle and bite forces - to examine the individual patient's biomechanics, eg, the influence of the periodontal ligament, the condition of the temporomandibular joints, atrophic processes, or the biomechanical situation of dental implants.DISCUSSION:By stepwise approximation towards the anatomical reality, the mandibular simulation will be advanced to a valuable tool for diagnosis and prognosis.