Oxygen-Releasing Hyaluronic Acid-Based Dispersion with Controlled Oxygen Delivery for Enhanced Periodontal Tissue Engineering.

Periodontitis is a chronic biofilm-associated inflammatory disease of the tooth-supporting tissues that causes tooth loss. It is strongly associated with anaerobic bacterial colonization and represents a substantial global health burden. Due to a local hypoxic environment, tissue regeneration is impaired. Oxygen therapy has shown promising results as a potential treatment of periodontitis, but so far, local oxygen delivery remains a key technical challenge. An oxygen (O2)-releasing hyaluronic acid (HA)-based dispersion with a controlled oxygen delivery was developed. Cell viability of primary human fibroblasts, osteoblasts, and HUVECs was demonstrated, and biocompatibility was tested using a chorioallantoic membrane assay (CAM assay). Suppression of anaerobic growth of Porphyromonas gingivalis was shown using the broth microdilution assay. In vitro assays showed that the O2-releasing HA was not cytotoxic towards human primary fibroblasts, osteoblasts, and HUVECs. In vivo, angiogenesis was enhanced in a CAM assay, although not to a statistically significant degree. Growth of P. gingivalis was inhibited by CaO2 concentrations higher than 256 mg/L. Taken together, the results of this study demonstrate the biocompatibility and selective antimicrobial activity against P. gingivalis for the developed O2-releasing HA-based dispersion and the potential of O2-releasing biomaterials for periodontal tissue regeneration.

The German S3 guideline on titanium hypersensitivity in implant dentistry: consensus statements and recommendations.

BACKGROUND: There is currently a lack of guidelines for clinicians regarding titanium hypersensitivity in implant dentistry. Diagnostic tests such as the epicutaneous test or the lymphocyte transformation test showed inconsistent results regarding reliability and validity and thus, evidence-based consensus recommendations regarding diagnostic and therapeutic options may be helpful in clinical decision-making. Therefore, the German S3 guideline on titanium hypersensitivity in implant dentistry was developed. FINDINGS: In the objectives, procedure, voting method and venue were defined and the consensus participants were invited. A systematic literature research was performed, and the overall quality of the evidence was rated according to the GRADE working group. Eight recommendations were formulated within the framework of a structured consensus conference under independent moderation and could be voted on with strong consensus (> 95% agreement). The formulated statements and recommendations were developed in small groups according to the guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) and were discussed and agreed upon in the plenum. CONCLUSIONS: For reasonable decision-making, a patient's clinical symptoms should be regarded as leading parameters, which are usually expressed by a local inflammatory reaction with subsequent disturbed osseous integration. Allergy tests, such as the epicutaneous test or the lymphocyte transformation test are not helpful in titanium intolerance assessments, since these tests indicate T cell-mediated allergies, which are not observed in titanium intolerance reactions. Other metals and impurities that might be present in superstructures or alloys also need to be considered as the cause of an intolerance reaction and a trigger for contact sensitization. In the case of a suspected titanium particle-related, local immunologically induced inflammatory reaction with subsequent impaired osseous integration, dental ceramic implants can be considered as a therapeutic option.

Diagnostic tests for titanium hypersensitivity in implant dentistry: a systematic review of the literature.

PURPOSE: There are rising concerns about titanium hypersensitivity reaction regarding dental endosseous implants. This review aims to summarize and compare the validity and reliability of the available dermatological and laboratory diagnostic tests regarding titanium hypersensitivity. The following PICO design was used: In Patients with titanium dental implants (P) does epicutaneous testing (ECT) (I), compared to lymphocyte transformation test (LTT) or Memory Lymphocyte Immunostimulation Assay (MELISA) (C) detect hypersensitivity reactions (O)? A literature search was performed including all studies dealing with this topic. Studies regarding orthopedic implants were excluded. METHODS: Three databases (MEDLINE PubMed, Cochrane Library, SciELO) were screened for suitable studies and an additional manual search was also performed. Literature regarding hypersensitivity reactions in orthopedic implants, hypersensitivity reactions regarding implants not related to dental or maxillofacial surgery, animal studies and in vitro studies were excluded. A quality assessment of all selected full-text articles was performed. Randomized, controlled trials were evaluated with the Cochrane Risk of Bias Tool I. Cohort studies were assessed according to the New Castle-Ottawa Scale and case series according to Moga et al. (Development of a quality appraisal tool for case series studies using a modified Delphi technique. 2012). RESULTS: 10 studies were included in the quantitative synthesis and available for the endpoint diagnostics of intolerance reactions to titanium dental implants: 2 clinical studies, 7 cohort studies and 1 case series. The potential for bias (internal validity) for these studies was overall rated as high. CONCLUSIONS: The study of the available literature regarding ECT and MELISA or LTT in patients with suspected titanium hypersensitivity showed inconsistent results in terms of reliability and validity and thus, those tests should be regarded cautiously. There is strong evidence that titanium hypersensitivity in dental implants is associated with innate immunity: unspecific pro-inflammatory responses due to particle induced hyperreactivity of macrophages or toxicological responses especially towards nanoparticles rather than activation of the adaptive immune system. Therefore, tests detecting allergies do not seem expedient and inflammatory clinical signs should be regarded as leading parameters.

The reproducibility of electronic color measurements of the marginal gingiva.

INTRODUCTION: This study evaluated the reproducibility of electronic color determination system evaluations of the marginal gingiva, which could be important for adhesive cervical fillings or prosthetic restorations that imitate the gingiva. MATERIAL AND METHODS: In 50 subjects, the L*, a*, and b* color coordinates were evaluated five times at a point in the marginal area of a central incisor using different electronic color determination systems: (SP) Shadepilot, (ES) Easyshade, (CE) Crystaleye, and (SV) X-Rite. The mean color difference (ΔE) and its standard deviation between the five measurements from each participant were calculated separately for each device. Further ICC for interdevice reliability was determined. RESULTS: The L*, a*, and b* color coordinates and ΔE values differed significantly among the systems (p < 0.001). Within each patient and measurement system, ΔE ranged from 1.4 to 3.2 (SD 1.1-2.5), L* from 2.6 to 5.7 (SD 2.6-5.7), a* from 11.9 to 21.3 (SD 3.6-3.9), and b* from 15.1 to 28.9 (SD 1.7-4.3). Interdevice reliability ranged between 0.675 and 0.807. CONCLUSIONS: Color determination of the marginal gingiva using the electronic tooth color determination systems tested herein showed limited reproducibility. The results obtained with the different measurement systems differed enormously. CLINICAL RELEVANCE: These results show that the electronic color measurement devices tested allow no high reproducible determination of color coordinates of the marginal gingiva.

Palatal steatocystoma simplex-a rare oral finding at an even rarer location.

Steatocystoma is a rare, benign cyst that mostly originates from a dermal sebaceous gland. It can be divided into steatocystoma multiplex-with multiple locations-and steatocystoma simplex occurring at a single site. The lesion is mostly located on the skin but can be found on other locations as well. This is the first case report of steatocystoma simplex that was found in the palate of a 37-year-old male. After resection with small safety margins and local wound dressing, no recurrence was detected during a follow-up of 1.5 years.

Unique manifestation of a multifocal adult rhabdomyoma involving the soft palate-case report and review of literature.

Extracardiac adult rhabdomyoma is a rare benign tumor, which mainly occurs in the head and neck region and originates from striated muscle tissue. We report a 64-year-old male with simultaneous diagnosis of three adult rhabdomyomas including the soft palate and performed a review the literature on multifocal adult rhabdomyoma (mARM). Including the present case, 27 mARM with a range of 2-7 lesions per patient were collected. Mean age at diagnosis was 65 years with a male (23) to female (4) ratio of 5.75:1. Common localizations were parapharyngeal space (35%), larynx (14%), submandibular (13%), paratracheal region (14%), tongue (10%), floor of mouth (9%), neck (3%) and soft palate (2%). In accordance to this review, this the first case of mARM with involvement of the soft palate.

Vascular architecture in free flaps: Analysis of vessel morphology and morphometry in murine free flaps.

The aim of this study was to analyze the development of vascular architecture as well as vascular morphometry and morphology of anastomosed microvascular free flaps. Free pectoral skin flaps were raised in 25 rats and anastomosed to the femoral vessels in the groin region. CD31 immunohistology was performed after 3, 7 and 12 d (each 5 animals each) to analyze microvessel density (MVD), microvessel area (MVA) and microvessel size (MVS). Microvascular corrosion casting was performed after 7 and 12 d (5 animals each) to analyze vessel diameter (VD), intervascular distance (IVD), interbranching distance (IBD), and branching angle (BA). Further on, sprout and pillar density as hallmarks of sprouting and intussusceptive angiogenesis were analyzed. Pectoral skin isles from the contralateral side served as controls. A significantly increased MVD was found after 7 and 12 d (p each <0.001). MVA was significantly increased after 3, 7 and 12 d (p each <0.001) and a significantly increased MVS was analyzed after 3 and 7 d (p each <0.001). VD and IVD were significantly increased after 7 and 12 d (p each <0.001). For IBD, a significantly increase was measured after 7 d (p < 0.001). For IBA, sprout and pillar density, no significant differences were found (p each ≥0.05). Significant changes in the vascular architecture of free flaps after successful microvascular anastomosis were seen. Since there was no evidence for sprout and pillar formation within the free flaps, the increased MVD and flap revascularization might be induced by the receiving site.

Hyperspectral imaging for monitoring of perfusion failure upon microvascular anastomosis in the rat hind limb.

BACKGROUND/PURPOSE: Objective, reliable and easy monitoring of microvascular tissue perfusion is a goal that was achieved for many years with limited success. Therefore, a new non-invasive hyperspectral camera system (TIVITA™) was tested for this purpose in an in vivo animal model. METHODS: Evaluation of tissue oxygenation during ischemia and upon reperfusion was performed in left hind limb in a rat model (n=20). Ischemia was induced by clamping and dissection of the superficial femoral artery. Reperfusion of the limb was achieved by microsurgical anastomosis of the dissected artery. Oxygenation parameters of the hind limb were assessed via TIVITA™ before and immediately after clamping and dissection of the artery, 3 and 30min after reperfusion as well as on postoperative days 1 and 2. Thereby, the non-operated hind limb served as control. As clinical parameters, the refill of the anastomosis as well as the progress of the affected leg were assessed. RESULTS: In 12 from 20 cases, TIVITA™ recorded a sufficient reperfusion with oxygenation parameters comparable to baseline or control condition. However, in 8 from 20 cases oxygenation was found impaired after reperfusion causing a re-assessment of the microvascular anastomosis. Thereby, technical problems like stenosis or local thrombosis were found in all cases and were surgically treated leading to an increased tissue oxygenation. CONCLUSIONS: The TIVITA™ camera system is a valid non-invasive tool to assess tissue perfusion after microvascular anastomosis. As it safely shows problems in oxygenation, it allows the clinician a determined revision of the site in time in order to prevent prolonged ischemia.

Advances toward fully automated in vivo assessment of oral epithelial dysplasia by nuclear endomicroscopy-A pilot study.

BACKGROUND: Uncertainties in detection of oral epithelial dysplasia (OED) frequently result from sampling error especially in inflammatory oral lesions. Endomicroscopy allows non-invasive, "en face" imaging of upper oral epithelium, but parameters of OED are unknown. METHODS: Mucosal nuclei were imaged in 34 toluidine blue-stained oral lesions with a commercial endomicroscopy. Histopathological diagnosis showed four biopsies in "dys-/neoplastic," 23 in "inflammatory," and seven in "others" disease groups. Strength of different assessment strategies of nuclear scoring, nuclear count, and automated nuclear analysis were measured by area under ROC curve (AUC) to identify histopathological "dys-/neoplastic" group. Nuclear objects from automated image analysis were visually corrected. RESULTS: Best-performing parameters of nuclear-to-image ratios were the count of large nuclei (AUC=0.986) and 6-nearest neighborhood relation (AUC=0.896), and best parameters of nuclear polymorphism were the count of atypical nuclei (AUC=0.996) and compactness of nuclei (AUC=0.922). Excluding low-grade OED, nuclear scoring and count reached 100% sensitivity and 98% specificity for detection of dys-/neoplastic lesions. In automated analysis, combination of parameters enhanced diagnostic strength. Sensitivity of 100% and specificity of 87% were seen for distances of 6-nearest neighbors and aspect ratios even in uncorrected objects. Correction improved measures of nuclear polymorphism only. The hue of background color was stronger than nuclear density (AUC=0.779 vs 0.687) to detect dys-/neoplastic group indicating that macroscopic aspect is biased. CONCLUSIONS: Nuclear-to-image ratios are applicable for automated optical in vivo diagnostics for oral potentially malignant disorders. Nuclear endomicroscopy may promote non-invasive, early detection of dys-/neoplastic lesions by reducing sampling error.

Evaluation of symptomatic maxillary sinus pathologies using panoramic radiography and cone beam computed tomography-influence of professional training.

BACKGROUND: A comparison of panoramic radiography (PAN) alone and PAN together with small field of view cone beam computed tomography (sFOV-CBCT) for diagnosis of symptomatic pathologies of the maxillary sinus was carried out by clinicians of different experience. METHODS: Corresponding radiographic images (PAN/sFOV-CBCT) of 28 patients with symptomatic maxillary sinus pathologies were chosen and analyzed by two general practitioners (GP), two junior maxillofacial surgeons (MS1), and three senior maxillofacial surgeons (MS2) via questionnaire. RESULTS: Visibility of maxillary pathologies in PAN was significantly different between the groups (GP 39%, MS1 48%, MS2 61%; p < 0.05). The number of incidental findings varied within examiner groups in PAN with a significant increase in MS2 (p = 0.027). The majority of examiners rated an additional sFOV-CBCT as "reasonable"/"required" with a significant influence of the examining groups (GP 98.2%, MS1 94.6%, MS2 80.9%; p = 0.008). In 58% of cases, an additional sFOV-CBCT was seen as "affecting therapy" with significant differences between the groups (GP 68%, MS1 50%, MS2 55%; p < 0.001). CONCLUSIONS: PAN alone is not sufficient for the evaluation of pathologies of the maxillary sinus. But, depending on the examiners' clinical experience, it remains a useful diagnostic tool. Along with the observers' training, significant benefits of an additional sFOV-CBCT for evaluation of symptomatic maxillary sinus pathologies were detected.

Bilateral Postoperative Cyst after Maxillary Sinus Surgery: Report of a Case and Systematic Review of the Literature.

Purpose. We present a case of a bilateral postoperative maxillary cyst (PMC) and discuss this with a systemic review. Case Report and Literature Review. A 68-year-old female with pain and swelling on the right side of the face. MRI and CT showed a cystic tumors of the right and left maxillary sinus. Radical maxillary surgery via a Caldwell-Luc procedure had been performed 55 years ago and bilateral PMC was diagnosed. The PubMed database was searched for PMC within the last 30 years. Results. Together with the current case, we found 23 reports including 284 patients describing PMC. It was diagnosed at a mean time of 22 years after causal surgery at a mean age of 47 years. Initial symptoms were mostly pain with or without swelling. The main radiological sign was a unilocular radiolucency with a slight preference for the left side. Discussion. PMC is a long-term complication that can occur after maxillary sinus surgery and a second surgical approach is required in order to stop cystic expansion. Therefore, patients' informed consent on this complication as well as a prolonged follow-up is recommended. Simple paranasal ultrasound or paranasal sinus plain radiography may lead to an earlier detection reducing interventional morbidity.

The enhancing effect of a laser photochemotherapy with cisplatin or zolendronic acid in primary human osteoblasts and osteosarcoma cells in vitro.

BACKGROUND: Photodynamic therapies (PDT) have become increasingly popular in the adjuvant treatment of different tumour entities. Chemotherapeutic agents, such as cisplatin may be used in combination with low-level laser therapy (LLLT) as laser photochemotherapy. The aim of this study was to investigate the effect of LLLT on cell bioviability of normal and malignant bone cells under chemotherapeutic conditions with either cisplatin or zolendronic acid in vitro. METHODS: Primary human osteoblasts (HOB) and an osteosarcoma cell line (Saos-2) were treated with different concentrations of zolendronic acid or cisplatin and irradiated twice with a diode laser (wavelength 670 nm, 120 s, energy outputs of 100mW/cm2 , continuous wave mode). Cell viability was tested by XTT-assay and via histomorphological analysis. RESULTS: LLLT alone increased bioviability for both cell lines. LLLT lowered HOB viability at the three highest concentrations of cisplatin and zolendronic acid. For Saos-2, LLLT reduced cell viability at every concentration of cisplatin. In cases of incubation with zolendronic acid, similar to osteoblasts, LLLT lowered cell viability at the highest concentration only. CONCLUSIONS: Based on the conditions of this study, laser photochemotherapy may be able to raise the cytotoxicity of cisplatin and zolendronic acid in benign and malignant bone cells. This could be of interest in the development of new therapeutic treatment modalities against neoplastic bone diseases like osteosarcoma.

The impact of GSTM1/GSTT1 polymorphism for the risk of oral cancer.

OBJECTIVES: Since development of oral squamous cell cancer (OSCC) is triggered by various noxa, different variants of the antioxidant glutathione S-transferases (GSTs) can counteract toxic compounds (e.g., tobacco smoke). Because different polymorphisms of GST are known to have an increased sensitivity to carcinogenic agents, the aim of this study was to analyze whether GSTM1 or GSTT1 polymorphisms increase the risk for the development of OSCC. MATERIALS AND METHODS: GSTM1 and GSTT1 polymorphism was examined in healthy volunteers (n = 93) and in patients with OSCC (n = 100) by PCR after brush biopsy of oral mucosa. Odds ratio (OR) was calculated to evaluate the risk of oral cancer development. RESULTS: GSTM1 and GSTT1 deletion was found in 57% (53/93) and 18% (17/93), respectively, in healthy patients, while the OSCC group showed 57% (57/100) for GSTM1 deletion and 22% (22/100) with a deletion of GSTT1. Odds ratio for GSTM1 polymorphism was 1.00 and for GSTT1 1.26. Comparing smokers and nonsmokers with GSTM1 deletion polymorphism, OR was 4.35, while smokers without GSTM1 deletion showed an OR of 1.45. Adapting these data to the smoking habits of the general population in Germany, the OR was 9.25 for smokers with a GSTM1 deletion and OR 6.68 for smokers without a GSTM1 deletion. In smokers with GSTT1 deletion polymorphism, OR was 1.6 (adapted to the smoking habits of the general population: OR 6.16) and 3.16 (OR 8.56) in smokers without deletion in GSTT1 gene. CONCLUSIONS: Analysis of GST-M1 polymorphism in smokers could help to identify patients with a higher risk for the development of oral cancer. CLINICAL RELEVANCE: Early detection of OSCC due to a close meshed monitoring program for patients with GST-M1 polymorphism could help to improve the patient outcome. For polymorphism investigations, the oral brush biopsy is a sufficient method to gain DNA material.

Vertical osteoconductive characteristics of titanium implants with calcium-phosphate-coated surfaces - a pilot study in rabbits.

INTRODUCTION: Osteoconductive characteristics of different implant surface coatings are in the focus of current interest. The aim of the present study was to compare the vertical osteoconductivity at the implant shoulder of supracrestal inserted calcium-phosphate coated implants (SLA-CaP) with conventional sand-blasted/acid-etched (SLA) implants in a rabbit model. MATERIALS AND METHODS: SLA-CaP and SLA implants were inserted bilaterally in the mandible of four rabbits in a split-mouth design. The implants were placed 2 mm supracrestal. After 3 weeks, at the left and right implant shoulder, the percentage of linear bone fill (PLF) as well as bone-implant contact (BIC-D) were determined. RESULTS: After 3 weeks, newly formed woven bone could be found at the shoulder of the most of both surface-treated implants (75%). PLF was significantly higher in SLA-CaP implants (11.2% vs. 46.5%; n = 8, p = .008). BIC-D was significantly increased in the SLA-CaP implants (13.0% vs. 71.4%; n = 8, p < .001) as well. CONCLUSION: The results of this study show for the first time that calcium-phosphate coated surfaces on supracrestal inserted implants have vertical osteoconductive characteristics and increase the bone-implant contact at the implant shoulder significantly in a rabbit model. In clinical long-term settings, these implants may contribute to a better vertical bone height.

Different culture media affect growth characteristics, surface marker distribution and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells.

BACKGROUND: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play an important role in modern tissue engineering, while distinct variations of culture media compositions and supplements have been reported. Because MSCs are heterogeneous regarding their regenerative potential and their surface markers, these parameters were compared in four widely used culture media compositions. METHODS: MSCs were isolated from bone marrow and expanded in four established cell culture media. MSC yield/1000 MNCs, passage time and growth index were observed. In P4, typical MSC surface markers were analysed by fluorescence cytometry. Additionally, chondrogenic, adipogenic and osteogenic differentiation potential were evaluated. RESULTS: Growth index and P0 cell yield varied importantly between the media. The different expansion media had a significant influence on the expression of CD10, CD90, CD105, CD140b CD146 and STRO-1. While no significant differences were observed regarding osteogenic and adipogenic differentiation, chondrogenic differentiation was superior in medium A as reflected by GAG/DNA content. CONCLUSIONS: The choice of expansion medium can have a significant influence on growth, differentiation potential and surface marker expression of mesenchymal stromal cells, which is of fundamental importance for tissue engineering procedures.

Clinical, therapeutic and prognostic features of osteosarcoma of the jaws - experience of 36 cases.

INTRODUCTION: Osteosarcoma of the jaws (OSJ) differs from osteosarcoma of other skeletal regions due to later development, a high mortality associated with the local disease, fewer incidences of metastases and its extreme rarity. In regard to clinical and pathological parameters as well as therapeutic approaches and prognosis, OSJ has not been specifically examined to date. In order to achieve a better understanding of this special malignancy, an evaluation of incidence, treatment and prognosis of patients with OSJ in our department over the past 38 years was conducted. MATERIALS AND METHODS: A retrospective analysis of patients with OSJ between 1972 and 2010 was performed. Information regarding patient characteristics, site of the lesion, main presenting symptoms, latency of initial diagnosis, treatment, histology, local recurrence, development of metastatic disease, duration of follow up and survival was obtained. The data were compared to the literature. RESULTS: Thirty-six patients (2-81 years, mean: 33.9, standard deviation: 21.3) were diagnosed and treated for OSJ (maxillar:mandibular nearly 1:2). Initial symptoms were local swelling (81%) and pain (47%). The latency period between fist symptoms and clinical presentation was 3.7 months (1-24). A radical resection alone was conducted in 15 patients. In nine patients, resection and radiotherapy was used. Resection with chemotherapy was the treatment of choice in seven patients. Five patients received a triple combination of resection, chemo- and radiation therapy. The osteoblastic subtype of osteosarcoma was most frequent (42%). In 15 cases (42%) local recurrences, in two cases (5%) metastasis were seen. Of these patients, 13 died within the observation period. One other patient (3%) died as a result of progressive pulmonary metastasis. A mean total survival rate of 61% could be seen whereas the highest survival rate (80%) was found in patients who were treated with neoadjuvant chemotherapy, radical resection and adjuvant radiation. Positive prognostic factors were a younger age and tumour-free resection margins. DISCUSSION: OSJ is a highly lethal tumour entity. According to the data at hand, therapy should possibly include chemotherapy, radical resection and irradiation. Nevertheless, due to the rarity of OSJ, information remains limited and the treatment of choice should be within the focus of clinical multi-centre studies.

A new method for volumetric evaluation of gingival recessions: a feasibility study.

BACKGROUND: This preliminary in vitro study, presented at the General Session of the International and American Association for Dental Research in 2010 (Barcelona, Spain), evaluates whether three-dimensional (3D) optical scanning and subsequent superimposing procedures could be used for reproducible volumetric evaluation of gingival recession. METHODS: Silicone impressions were taken of mandibular and maxillary master casts, and eight stone replicas of each master cast were produced. Each replica was scanned 10 times with a 3D optical system, and 3D datasets representing the computer-aided design reference models were calculated using a triangulation method. Marks designating gingival recession were scratched into the anterior segments of the replicas. The modified replicas were then scanned 10 times, and 3D datasets were calculated and subsequently superimposed. Differences in the volume of the gingival recession were recorded with reference to the initial data. RESULTS: The determination of gingival recession volume was highly reproducible. For all replicas, the 3D optical method showed small standard deviations and intraclass correlation coefficients between 0.997 and 0.999. CONCLUSIONS: This new method allows the reproducible volumetric evaluation of gingival recession marks on stone replicas. Additional clinical trials are necessary to confirm these in vitro findings. This method allows the operator to control the volumetric progression of periodontal soft tissue, for example, after root coverage procedures and to detect relapses at an early stage.