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Background: In reconstructive surgery, improvements are needed in the effective teaching of free flap surgery. There is a need for easily accessible and widely available training without high financial costs or ethical concerns while still providing a realistic experience. Our aim was to develop an appropriate training model for microvascular flaps., Methods: We identified pig head halves as most appropriate regarding availability, cost, and realism. These accrue largely by the food industry, so no animals need to be sacrificed, making it more ethical from an animal welfare perspective. We evaluated the suitability as flap donor site and analyzed the vascular anatomy of 51 specimens., Results: Anatomical evaluation revealed a reliable and constant vascular anatomy, allowing the design of a flap model that can effectively illustrate the entire process of microvascular flap surgery. The process was divided into 6 key steps. The flap can be harvested after marking the vascular pedicle 5.3 cm from the lateral corner of the mouth. Skin island design and subsequent tissue dissection follow until a fasciocutaneous flap is raised, similar to a radial flap. Upon completion of flap harvesting, it can be freely transferred for defect reconstruction. Microvascular anastomosis can be performed on recipient vessels in the cervical region, and the difficulty can be individually adjusted., Conclusions: The developed training model is a reasonable compromise in terms of surgical realism, availability, didactic value, and cost/time effectiveness. We believe it is a powerful and effective tool with high potential for improving surgical education and training., (© 2024. The Author(s).)

Since its introduction in 1968, the TNM (tumor, node, metastasis) classification established by the International Union Against Cancer has provided a consistent framework for staging of oral squamous cell carcinoma (OSCC). The introduction of the 8th edition in 2017 brought about significant modifications, encompassing the integration of depth of invasion (DOI) and extranodal extension (ENE) into the T and N classifications. Further, the UICC the criteria for the T3 and T4a categories were amended in 2020. This study aimed to evaluate the impact of reclassification on staging and, subsequently, the survival of patients with OSCC. Primary OSCCs from 391 patients were classified according to the 7th and revised 8th UICC editions (2020). Stage migration was assessed, and stage-specific progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The log-rank test was used to compare the different stages. Cox-proportional hazard modeling was used to compare the two editions. Incorporating the DOI into the T classification resulted in an upstaging of 77 patients, constituting 19.69% of the cohort. In addition, 49 (12.53%) patients experienced an upstaging when considering ENE in the N classification. Consequently, 103 patients underwent upstaging in UICC staging, accounting for 21.74% of cases. Upstaging mainly occurred from stage III to IVA (26.92%) and from stage IVA to IVB (31.78%). Upon comparing the categories in survival analysis, significant differences in OS and PFS were especially observed between stage IVB and lower stages. When examining the hazard ratios, it became evident that UICC 8 stage IVB is burdened by a 5.59-fold greater risk of disease progression than stage I. Furthermore, UICC 8 stage IVB exhibits a 3.83 times higher likelihood of death than stage I disease. We demonstrated significant stage migration from the 7th to the revised 8th UICC edition. Overall, incorporating DOI and ENE into the T and N classifications represents a substantial clinical advancement, leading to a more accurate staging of OSCC patients. Both staging systems exhibited statistically significant discrimination between stages; however, the 8th UICC edition allowed for a more precise categorization of patients based on their prognosis and led to enhanced hazard discrimination, particularly within higher stages., (© 2024. The Author(s).)

Objectives: Management of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival., Material and Methods: A retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach., Results: Four hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor., Conclusions: Overall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients., Clinical Relevance: None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes., (© 2024. The Author(s).)

Objective: Accurate preoperative prediction of lymph node (LN) status plays a pivotal role in determining the extension of neck dissection (ND) required for patients with oral squamous cell carcinoma (OSCC). This study aims to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) in detecting LN metastases (LNMs) and to explore clinicopathological factors associated with its reliability., Methods: Data from 239 patients with primary OSCC who underwent preoperative CT and subsequent radical surgery involving ND were retrospectively reviewed. Suspicious LNs were categorized into three groups: accentuated (< 10 mm), enlarged (≥ 10 mm), and melted. Statistical analysis encompassing correlation and comparative analysis, and determination of sensitivity, specificity, PPV, and NPV were performed., Results: Overall, sensitivity was significantly higher in the accentuated LNs group (83.54%) compared to the melted LNs group (39.24%, p < 0.05, t test). Conversely, specificity was significantly higher in the melted LNs group (98.19%) compared to the accentuated LNs group (55.15%, p < 0.05, t test). Accentuated LNs exhibited a false negative rate of 13.00%. False positive rates were 51.80%, 30.26% and 8.82%, respectively. Diagnostic accuracy for detecting LNMs in level IIa and IIb exceeded that of level III. Patients with solely accentuated LNs were more likely to have a small, well-differentiated tumor. However, no distinctions emerged in terms of the occurrence of T4 tumors among the three groups., Conclusion: CT proves sufficient to predict LNMs in patients with OSCC. Looking ahead, the potential integration of artificial intelligence and deep learning holds promise to further enhance the reliability of CT in LNMs detection. However, this prospect necessitates further investigation., (© 2023. The Author(s).)

Background: This retrospective case series study aims to demonstrate a salvage technique for the treatment of carotid blow-out syndrome (CBS) in irradiated head and neck cancer patients with a vessel-depleted neck., Methods: Between October 2017 and October 2021, two patients (N = 2) with CBS were treated at our institution in a multidisciplinary approach together with the Department of Vascular Surgery. Patients were characterized based on diagnoses, treatment procedures, and the subsequent postoperative course., Results: Surgical emergency intervention was performed in both cases. The transition zone from the common carotid artery (CCA) to the internal carotid artery (ICA) was resected and reconstructed with a xenogic (case 1) or autogenic (case 2) interposition (end-to-end anastomosis). To allow reconstruction of the vascular defect, an additional autologous vein graft was anastomosed to the interposition graft in an end-to-side technique, allowing arterial anastomosis for a free microvascular flap without re-clamping of the ICA. Because of the intraoperative ICA reconstruction, none of the patients suffered a neurological deficit., Conclusions: The techniques presented in the form of two case reports allow for acute bleeding control, cerebral perfusion, and the creation of a vascular anastomosis option in the vessel-depleted neck.

Objectives: The present radiological observational controlled study aims to evaluate the impact of secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) as well as the duration of dialysis on the mineralization of the mandible by standardized qualitative evaluation of digital panoramic radiographs., Methods: Panoramic radiographs of CKD patients with SHPT and healthy controls were used for the qualitative analysis of the mandibular cortical index (MCI), the trabecular bone pattern (TBP), and calcification and resorption foci. Radiomorphometric indices were correlated to biochemical parameters and the duration of dialysis using the Spearman Rho test. Group comparisons were conducted using the Mann-Whitney U test and Fisher's exact test at a significance level of α ≤ 0.05. Interrater reliability of two physicians was estimated using Cohen's kappa., Results: Inclusion and exclusion criteria were fulfilled by N = 41 patients. Statistically significant differences in the MCI (p < 0.001) as well as the TBP (p = 0.002) could be detected for the experimental group in comparison to the healthy control group. Focusing on calcification and resorption foci, no statistically significant difference could be detected between the groups (p = 0.244). The level of the detected parathyroid hormone (PTH) significantly correlated with TBP (Rho = 0.338; p = 0.031), while no significant relationship between TBP and the duration of the dialysis could be found., Conclusions: Patients with SHPT due to CKD show statistically significant bone changes in the panoramic radiograph, whereby the grade of trabecular bone change correlates to PTH values., (© 2022. The Author(s).)

When intracellular, pathogenic Salmonella reside in a membrane compartment composed of interconnected vacuoles and tubules, the formation of which depends on the translocation of bacterial effectors into the host cell. Cytoskeletons and their molecular motors are prime targets for these effectors. In this study, we show that the microtubule molecular motor KIF1Bβ (a splice variant of KIF1B), a member of the kinesin-3 family, is a key element for the establishment of the Salmonella replication niche as its absence is detrimental to the stability of bacterial vacuoles and the formation of associated tubules. Kinesin-3 interacts with the Salmonella effector SifA but also with SKIP (also known as PLEKHM2), a host protein complexed to SifA. The interaction with SifA is essential for the recruitment of kinesin-3 on Salmonella vacuoles whereas that with SKIP is incidental. In the non-infectious context, however, the interaction with SKIP is essential for the recruitment and activity of kinesin-3 only on a fraction of the lysosomes. Finally, our results show that, in infected cells, the presence of SifA establishes a kinesin-1 and kinesin-3 recruitment pathway that is analogous to and functions independently of that mediated by the Arl8a and Arl8b GTPases. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Defects in head and neck regions are standardly treated with microvascular grafts, such as free scapular (SFF) and fibular flaps (FFF), which are subject to a certain amount of bone resorption over time. The aim of this study was the 3-dimensional evaluation of bone resorption volume in both grafts. Over a period of 10 years, computed tomograms (CT) of patients with mandibular reconstructions with SFFs and FFFs were examined. The respective grafts were segmented as well as 3-dimensionally measured. Furthermore, factors such as gender, age, nicotine abuse, previous disease with type 2 diabetes, and adjuvant therapies, were examined for their influence. A total of 211 CT scans from 67 patients (40 SFFs and 27 FFFs) were included in the study. SFFs showed slightly higher median bone volumes (87.60% at 730 days and 86.55% at 1500 days) than FFFs (84.40% at 730 days and 82.10% at 1500 days). When final volumes were considered, FFFs had higher mean volume values (88.22%) than SFFs (83.82%), with significant correlation between resorption volume and time progression (r = 0.357, p = 0.024). All previously mentioned factors had no significant effect on bone resorption. Bone volumes of FFFs showed postoperative volume reductions similar to those of SFFs, with isolated SFFs having markedly lower volume values. The choice of a microvascular graft for reconstruction in the mandible proves difficult regarding bone resorption. The presented results may support decisions about future transplantations., (Copyright © 2022 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: This retrospective study evaluates intraoral surgical and conservative treatment need in patients with a chronic kidney end-stage disease, depending on the duration of dialysis treatment and the causative nephrological disease., Material and Methods: This study is based on data of patients referred to the Department of Oral and Maxillofacial Surgery of the University Hospital Erlangen, Germany, prior to kidney transplantation between January 2015 and March 2020. The necessity for oral surgical or dental therapy was determined by clinical and radiological examinations. Data on renal replacement therapy, cause of underlying renal disease, lifestyle, and general health were collected., Results: Data of N = 89 patients demonstrated that surgical treatment need depends on dialysis duration (p = 0.042). Patients, who had been dialyzing for 2 to 3 years showed the highest need for surgical intervention (80.0%; p = 0.024), followed by dialysis patients with a dialysis time of more than 3 years (48.1%). Similarly, dialysis patients in the second or third year of dialysis had the highest need for conservative treatment (73.3%; p > 0.05), followed by 55.6% of dialysis patients in the third year of dialysis., Conclusions: Operative and conservative treatment is essential to optimize subsequent kidney transplantation. The greatest necessity could be detected for patients in the second and third years of dialysis., Clinical Relevance: Oral health addressing surgical and conservative treatment need depends on the duration of dialysis in patients with a chronic kidney end-stage disease., (© 2021. The Author(s).)

Background: The oral health of organ transplanted patients before organ re-transplantation is largely unknown. This retrospective clinical study evaluates the necessity for intraoral surgical intervention and/or conservative treatment in candidates awaiting organ re-transplantation, both for graft failure and for reasons of another upcoming solid organ transplantation (renal or non-renal)., Methods: From January 2015 to March 2020 n = 19 transplant recipients in evaluation on the waiting list for solid organ re-transplantation could be included in the retrospective case series study. Using clinical and radiological examinations, necessity for oral surgical or conservative dental treatment was evaluated. On the basis of anamnesis data, current kidney function, renal replacement treatment (RRT), and medication, a risk profile for several patient subgroups was created., Results: The clinical and radiological examinations showed a conservative and/or surgical treatment need in n = 13 cases (68.42%). In n = 7 cases (36.84%) surgical intervention was recommended due to residual root remnants (n = 5), unclear mucosal changes (n = 1), and periimplantitis (n = 1). In n = 16 recipients (84.2%) RRT (n = 15 hemodialysis; n = 1 peritoneal dialysis) had been performed. N = 14 recipients (73.68%) received immunosuppressants. In n = 1 patient (5.3%) displayed intraoral and n = 4 patients (21.1%) extraoral neoplasms due to drug-induced immunosuppression., Conclusions: Solid organ transplant recipients with renal failure present a complex treatment profile due to a double burden of uremia plus immunosuppressants. In cases of surgical treatment need a hospitalized setting is recommended, where potentially necessary follow-up care and close cooperation with disciplines of internal medicine is possible in order to avoid surgical and/or internal complications., (© 2021. The Author(s).)

Objectives: The aim of this study was to investigate if bone regeneration can be promoted by homologous transplantation of STRO-1 sorted (STRO-1+) porcine tooth germ mesenchymal stem cells (TGSCs) with the combination of polyethylenglycol (PEG)-based hydrogel and biphasic calcium phosphate (BCP) scaffolds., Material and Methods: TGSCs were isolated from impacted third molars of domestic pigs. Nine critical-sized defects were created as (1) untreated defect; filled with (2) autogenous bone; (3) BCP + PEG; (4) BCP + PEG + unsorted TGSCs; (5) BCP + unsorted TGSCs; (6) BCP + PEG + STRO-1-sorted TGSCs; (7) BCP + STRO-1-sorted TGSCs; (8) BCP + PEG + osteogenic induced unsorted TGSCs; and (9) BCP + PEG + osteogenic induced STRO-1-sorted TGSCs in 20 domestic pigs. CM-DiI labelling was used to track cells in vivo. Histomorphometric assessment of new bone formation was achieved by toluidine blue O staining and microradiography after 1, 2, 4 and 12 weeks posttransplantation., Results: Complete healing was achieved in all defects although defects with PEG hydrogel presented better bone formation while STRO-1+ and unsorted TGSCs showed similar ability to form new bone after 12 weeks. Transplanted cells were seen in defects where PEG hydrogel was used as carriers in contrast to defects treated with cells and only bone grafts., Conclusions: PEG hydrogel is an efficient carrier for homologous stem cell transplantation. TGSCs are capable of promoting bone healing in critical-sized defects in combination with bone graft and PEG hydrogel., Clinical Relevance: This study provides information about the importance of the delivery vehicle for future translational stem cell delivery approaches.

In the article by Möst et al., entitled "Osseous ingrowth in allogeneic bone blocks applied for vertical bone augmentation: a preclinical randomized controlled study.

Objectives: The aim of the present study was the qualitative and quantitative evaluation of osseous graft consolidation using allogeneic bone blocks for vertical bone augmentation in an animal model., Material and Methods: Standardised allogeneic and autologous bone blocks were fixed on the frontal skull of 20 adult female pigs and covered with a resorbable collagen membrane. Animals were sacrificed after 2 and 6 months. Specimens were histologically and histomorphometrically analysed focusing on the amount of vital bone, residual bone substitute material and connective tissue. Furthermore, the amount of expression of bone matrix proteins (collagen type I and osteocalcin) and de novo vessel formation (von Willebrand factor) were quantified by immunohistochemistry., Results: Significantly more allogeneic bone blocks failed for both evaluation time points (p < 0.05). Allogeneic blocks showed significantly less vital bone with more connective tissue formation compared to autologous bone blocks. Increased vessel formation could be detected for both evaluation time points in the contact area of autologous bone with local bone. The expression of collagen type I and osteocalcin was significantly lower in the allogeneic bone graft., Conclusions: Allogeneic cancellous bone blocks showed a significantly higher failure rate compared to autologous bone blocks. Allogeneic bone blocks seemed to negatively affect bone formation or negatively influence the host in the long term, and increased connective tissue formation and block loss should be anticipated., Clinical Relevance: In order to maintain patient safety and treatment success clinicians should be persuaded to make a conscious choice of the applied biomaterials with regard to their components and structure.

Objectives: The preclinical study aimed to establish a standardized preclinical model to investigate osseous graft consolidation in defect configurations of limited regenerative capacity., Material and Methods: Critical size defects (CSD) were prepared and titanium tubes inserted for defect separation from local bone in the forehead area of 18 pigs. Defects were filled with demineralized bovine bone mineral (DBBM) or served as empty controls and were covered with a resorbable collagen membrane (CM) or left untreated. Six randomly selected pigs were sacrificed after 4, 8 and 12 weeks. Specimens were histologically and histomorphometrically analysed focusing on newly formed bone (NFB), demineralized bovine bone mineral (DBBM) and soft tissue (ST) proportions., Results: Four weeks after defect preparation, no statistically significant difference concerning NFB quantity could be detected within the groups. Defects covered with the CM showed lower amounts of DBBM. After 6 and 12 weeks, defects augmented with DBBM in combination with a CM (8 weeks: 43.12 ± 4.31; 12 weeks: 43.05 ± 3.01) showed a statistically significant higher NFB rate compared to empty control defects covered with 8 weeks: 7.66 ± 0.59; 12 weeks or without a CM; 8 weeks: 8.62 ± 2.66; 12 weeks: 18.40 ± 2.40. CM application showed no significant impact on osseous defect regeneration or soft tissue formation. Superior NFB could be detected for basal aspect for several evaluation time points., Conclusions: The modification of CSD with titanium tubes represents a suitable model to imitate a one-wall defect regeneration situation., Clinical Relevance: The established model represents a promising method to evaluate graft consolidation in one-wall defect configuration.

The use of nanoscale surface modifications offers a possibility to regulate the bacterial adherence behavior. The aim of this study was to evaluate the influence of nanoporous anodic aluminum oxide of different pore diameters on the bacterial species Streptococcus mitis and Streptococcus mutans. Nanoporous anodic aluminum oxide (AAO) surfaces with an average pore diameter of 15 and 40 nm, polished pure titanium and compact aluminum oxide (alumina) samples as reference material were investigated. S. mitis and mutans were evaluated for initial adhesion and viability after an incubation period of 30 and 120 min. After 30 min a significantly reduced growth of S. mitis and mutans on 15 nm samples compared to specimens with 40 nm pore diameter, alumina and titanium surfaces could be observed (p < .001). Even after 120 min incubation there was a significant difference between the surfaces with 15 nm pore diameter and the remaining samples (p < .001). AAO surfaces with a small pore diameter have an inhibitory effect on the initial adhesion of S. mitis and mutans. The use of such pore dimensions in the area of the implant shoulder represents a possibility to reduce the adhesion behavior of these bacterial species., (© 2019 Wiley Periodicals, Inc.)

Aim: To compare 10-month histological and immunohistological outcomes after soft tissue thickening around teeth with a porcine collagen matrix (CM) versus a subepithelial connective tissue graft (SCTG)., Material and Methods: In eight beagle dogs, soft tissue thickening of the buccal gingiva of upper canines was performed with the SCTG or the CM. Connective tissue thickness (CTT) was histomorphometrically measured in the augmented regions. The augmented connective tissues were also histologically characterized and the collagen I and vascular endothelial growth factor (VEGF) expressions immunohistologically quantified., Results: CTT significantly differed between groups (SCTG: 1.32 mm ± 0.44 mm; CM: 1.06 mm ± 0.27 mm; p = .008). Descriptive histological analyses revealed mature connective tissue that did not differ between groups. Immunohistological quantification of collagen I and VEGF expressions in the connective tissue also revealed no significant inter-group differences (collagen I: SCTG, 32.64% ± 7.09% vs. CM, 30.57% ± 7.83%; VEGF: SCTG, 39.06% ± 7.27% vs. CM, 37.15% ± 9.80%)., Conclusion: SCTG is superior to CM with regard to CTT in this experimental model. The CM and the SCTG lead to comparable connective tissue quality ten months after connective tissue thickening., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The following note was inadvertently omitted from the published paper: This work was performed in (partial) fulfillment of the requirements for the first author's obtaining the degree Dr. med. dent.

Cells infected with Salmonella are characterised by the appearance of membrane tubular structures that stretch from the bacterial vacuole. The formation of these tubules requires the translocation of Salmonella effector proteins within the infected cell. Different types of Salmonella-induced tubules with varying host protein compositions have been identified. This variability probably reflects the ability of these tubules to interact with different host compartments. Membrane tubules decorated with effector proteins but essentially devoid of host proteins and named LAMP1-negative (LNT) were observed. LNTs wrap around LAMP1-positive vesicles and may promote recruitment of lysosomal glycoproteins to bacterial vacuole and the formation of a replication niche. We conducted a biochemical and functional characterisation of LNTs. We show that the effector proteins SseF and SseG are necessary for their formation. The absence of these tubules is associated with decreased recruitment of LAMP1 to SCVs, decreased intracellular replication of Salmonella, and decreased virulence in mice. We found that the process leading to the recruitment of lysosomal glycoproteins to tubules involves the C-terminal domain of the effector protein SifA and the GTPase Arl8b. Overall, these data suggest that Salmonella-induced tubules promote the establishment of the replication niche by promoting recruitment of host proteins to the bacterial vacuole., (© 2018 John Wiley & Sons Ltd.)

Objectives: This study aimed to identify anatomical areas where resections of oral squamous cell carcinomas (OSCC) are significantly associated with close or positive margins., Materials and Methods: This retrospective study included 330 patients with a primary OSCC from 2010 to 2015. Patient and tumour data were categorised into three groups by R-status (R0 [clear], ≥ 5 mm, 185 patients [56.06%]; R1 [positive], < 1 mm, 24 patients [7.27%]; and R0 [close], 1-5 mm, 121 patients [36.67%])., Results: Areas where resections were significantly associated with close or positive margins were the hard palate (p < 0.001), buccal mucosa (p = 0.03), floor of the mouth (p = 0.004), lower alveolar ridge (p = 0.01), retromolar triangle (p = 0.005), and dorsal tongue (p = 0.02)., Conclusions: Anatomical areas were identified in the oral cavity where it is challenging to resect OSCCs with an adequate safety margin., Clinical Relevance: These results may enable surgeons to achieve a postulated safe distance during tumour resection, leading to a survival benefit for patients.

Objectives: This study aimed to assess the impact of different abutment materials on peri-implant tissue regeneration after surgical treatment of peri-implantitis in a large animal model., Material and Methods: Titanium implants (n = 51) were inserted in the upper and lower jaw of eight beagle dogs and a peri-implant infection was induced. After two months the peri-implant infection was surgically treated and abutments with different surfaces (Ti-2: n = 14; CoCrMb: n = 13; Ag-modified Ti-4: n = 14; Ti-4 control: n = 10) were applied. Clinical attachment level (CAL), modified sulcus bleeding index (mBI), bleeding on probing (BoP), and the sulcus fluid flow rate (SFFR) were determined 4, 8, and 12 weeks after surgical treatment to document the peri-implant tissue reaction., Results: Superior levels for CAL and mBI were found with the Ti-4 control and the Ag-modified abutments, with the Ag-modified abutments showing the best values after 12 weeks. Lowest SFFR values compared with the other treatment groups underlined the superior soft tissue reaction adjacent to Ag-modified abutments. After 12 weeks inferior CAL, SFFR, BOP and mBI values were documented for the Ti-2 surface., Conclusion: Within limitations of the study, Ag-modified abutments lead to superior tissue reactions. Further studies are needed to investigate the properties of abutment materials., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: The overall aim of the study was to investigate a biofunctionalized implant surface with electrochemically deposition of hydroxyapatite and the synthetic peptide (P-15) and its effect on osseointegration., Material and Methods: Three modified implant types of ANKYLOS ® C/X implants were used; (1) machined implants used as negative control (M, n = 20), (2) implants with the FRIADENT ® plus surface (grit blasted and acid-etched) used as positive control (P, n = 20), and (3) implants with a biomimetic surface consisting of hydroxyapatite and the synthetic 15 aminoacids containing peptide P-15 (BP, n = 40). The implants were randomly inserted in the mandibles of 10 beagle dogs following 4 months after tooth extraction (P1-P4). Three animals were sacrificed 2 and 7 days after implant insertion, respectively, and four animals were sacrificed 6 months post implant insertion. Bone-to-implant contacts (BICs) were analyzed via histomorphometrical analyses at five different region of interests (ROIs); two at the middle part on either side of the implant (ROI 1/4), two at the apical part of the implant at each side (ROI 2/3), and one at the tip of the implant (ROI 5)., Results: All implant surfaces showed a high level of osseointegration and osteoconductivity. The cumulative implant survival rate (CSR) was 93.8%, 100% in the M, 85% in the P, and 95% in the BP group. No statistical difference in BICs at ROI 1/4, 2/3, and 5 could be shown between implant types following 2 and 7 days of healing. BIC values increased in all groups over time. After 6 months of healing the BP group showed superiority in BIC in ROI 2/3 (73.2 ± 15.6%) compared to the P (48.3 ± 10.6%) and M group (66.3 ± 30.2%) with a significant difference between BP and P (P = 0.002)., Conclusion: It is hypothesized, that the surface biofunctionalization improves peri-implant bone formation and remodeling, leading to an increased bone-to implant contact. However, within the limitations of the study set-up no benefit in the early phase of osseointegration could be established for dental implants with P-15 containing surface in this study., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Porcine collagen matrices are proclaimed being a sufficient alternative to autologous free gingival grafts (FGG) in terms of augmenting the keratinized mucosa. The collagen matrix Mucograft ® (CM) already showed a comparable clinical performance in the early healing phase, similar histological appearance, and even a more natural appearance of augmented regions. Predictability for long-term stability does not yet exist due to missing studies reporting of a follow-up >6 months., Material and Methods: The study included 48 patients with atrophic edentulous or partially edentulous lower jaw situations that had undergone an implant treatment. In the context of implant exposure, a vestibuloplasty was either performed with two FGGs from the palate (n = 21 patients) or with the CM (n = 27 patients). Surgery time was recorded from the first incision to the last suture. Follow-up examinations were performed at the following time points: 10, 30, 90, and 180 days and 1, 2, 3, 4, and 5 years after surgery. The width of keratinized mucosa was measured at the buccal aspect of each implant, and augmented sites were evaluated in terms of their clinical appearances (texture and color)., Results: The groups showed similar healing with increased peri-implant keratinized mucosa after surgery (FGG: 13.06 mm ± 2.26 mm and CM: 12.96 mm ± 2.86 mm). The maximum follow-up was 5 years (5 patients per group). After 180 days, the width of keratinized mucosa had decreased to 67.08 ± 13.85% in the FGG group and 58.88 ± 14.62% in the CM group with no statistically significant difference. The total loss of the width of keratinized mucosa after 5 years was significant between the FGG (40.65%) and the CM group (52.89%). The CM group had significantly shorter operation times than the FGG group. Augmented soft tissues had a comparable clinical appearance to adjacent native gingiva in the CM group. FGGs could still be defined after 5 years., Conclusions: The FGG and the CM are both suitable for the regeneration of the peri-implant keratinized mucosa with a sufficient long-term stability. With the CM, tissue harvesting procedures are invalid, surgery time can be reduced, and regenerated tissues have a more esthetic appearance., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: This study evaluates a porcine collagen matrix (CM) for soft tissue thickening in comparison to the subepithelial connective tissue graft (SCTG)., Material and Methods: In eight beagle dogs, soft tissue thickening was performed at the buccal aspects of the upper canines (SCTG and CM). Impressions were taken before augmentation (i1), after surgery (i2), after one (i3), three (i4) and ten month (i5). Casts were optically scanned with a 3D scanner and each augmented region (unit of analysis) evaluated (primary outcome variable: volume increase in mm(3) ; secondary outcome variables: volume increase in percent, mean and maximum thickness increases in mm)., Results: 3D tissue measurements after surgery revealed a significant higher volume increase in the CM (86.37 mm(3)  ± 35.16 mm(3) ) than in the SCTG group (47.65 mm(3)  ± 17.90 mm(3) ). After 10 months, volume increase was non-significant between groups (SCTG:11.36 mm(3)  ± 9.26 mm(3) ; CM: 8.67 mm(3)  ± 13.67 mm(3) ). Maximum soft tissue thickness increase (i1-i5) was 0.66 mm ± 0.29 mm (SCTG) and 0.79 mm ± 0.37 mm (CM) with no significant difference., Conclusions: Ten months after soft tissue thickening, the CM is statistically non-inferior to the SCTG in terms of soft tissue volume and thickness increase. Further 3D studies are needed to confirm the data., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The study aims to establish a peri-implant dehiscence-type bone defect in a diabetic animal model of human bone repair and to quantify the influence of diabetes on peri-implant bone regeneration., Material and Methods: Experimental diabetes was induced in three domestic pigs by streptozotocin. Three animals served as healthy controls. After 12 months four standardized peri-implant dehiscence bone defects were surgically created in the ramus mandibulae. The animals were sacrificed after 90 days. Samples were histologically analyzed to quantify new bone height (NBH), bone-to-implant-contact (BIC), area of newly formed bone (NFB), bone-density (BD), and bone mineralization (BM) in the prepared defect (-D) and in a local control region (-L)., Results: After 90 days, diabetic animals revealed a significantly lower BIC (p = 0.037) and BD (p = 0.041) in the defect area (-D). NBH and BM-D differences within the groups were not significant (p > 0.05). Significant more NFB was measured in the healthy control group (p = 0.046). In the region of local bone BIC-L was significant less in the diabetic group (p = 0.028). In the local control region BD-L and BM-L was lower in the diabetic group compared to the healthy control animals (p > 0.05)., Conclusion: Histological evidence indicates impaired peri-implant defect regeneration in a diabetic animal model., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: This investigation focused on histological characteristics and 5-year implant survival after sinus floor augmentation with anorganic bovine bone (ABB, Bio-Oss) and ABB plus autologous bone (AB) with a ratio of 1/1., Material and Methods: Nineteen consecutive patients with bony atrophy of the posterior edentulous maxilla and a vertical bone height ≤4 mm were prospectively included in this study. In the first surgical stage, the maxillary sinus was non-randomized either augmented with ABB alone (n = 12) or a 1/1 mixture of ABB and AB (n = 7). After a mean healing period of 167 days, biopsies were harvested in the region of the grafted sinus with a trephine burr and implants were placed simultaneously, ABB n = 18 and ABB + AB n = 12. The samples were microradiographically and histomorphometrically analyzed judging the newly formed bone (bone volume, BV), residual bone substitute material volume (BSMV), and intertrabecular volume (soft tissue volume, ITV) in the region of the augmented maxillary sinus. Implant survival was retrospectively evaluated from patient's records., Results: No significant difference in residual bone substitute material (BSMV) in the ABB group (31.21 ± 7.74%) and the group with the mixture of ABB and AB (28.41 ± 8.43%) was histomorphologically determined. Concerning the de novo bone formation, also both groups showed statistically insignificant outcomes; ABB 26.02 ± 5.23% and ABB + AB 27.50 ± 6.31%. In all cases, implants were installed in the augmented sites with sufficient primary stability. After a mean time in function of 5 years and 2 months, implant survival was 93.75% in the ABB and 92.86% in the ABB + AB group with no statistically significant differences., Conclusion: The usage of ABB plus AB to a 1/1 ratio leads to an amount of newly formed bone comparable with the solitary use of ABB after grafting of the maxillary sinus. Considering that ABB is a non-resorbable bone substitute, it can be hypothesized that this leads to stable bone over time and long-term implant success. Importantly, in the sole use of ABB, bone grafting and therefore donor site morbidities can be avoided., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The virulence of Salmonella relies on the expression of effector proteins that the bacterium injects inside infected cells. Salmonella enters eukaryotic cells and resides in a vacuolar compartment on which a number of effector proteins such as SifA are found. SifA plays an essential role in Salmonella virulence. It is made of two distinct domains. The N-terminal domain of SifA interacts with the host protein SKIP. This interaction regulates vacuolar membrane dynamics. The C-terminal has a fold similar to other bacterial effector domains having a guanine nucleotide exchange factor activity. Although SifA interacts with RhoA, it does not stimulate the dissociation of GDP and the activation of this GTPase. Hence it remains unknown whether the C-terminal domain contributes to the function of SifA in virulence. We used a model of SKIP knockout mice to show that this protein mediates the host susceptibility to salmonellosis and to establish that SifA also contributes to Salmonella virulence independently of its interaction with SKIP. We establish that the C-terminal domain of SifA mediates this SKIP-independent contribution. Moreover, we show that the two domains of SifA are functionally linked and participate to the same signalling cascade that supports Salmonella virulence.

Objectives: This study aimed to compare autologous bone (AB), bovine bone (BB), and equine bone (EB) blocks with regard to de novo bone formation, connective tissue, and residual bone substitute material portions in a standardized defect animal model., Material and Methods: In the frontal skull of 20 pigs, 106 standardized cylindrical "critical size defects" were prepared. Defects were randomly filled with AB, BB, and EB blocks. After a healing period of 30 and 60 days, de novo bone formation, residual bone substitute material, and connective tissue portion was assessed by means of histomorphometry (Toluidine blue O staining). Mann-Whitney U-tests were used to evaluate differences between the groups., Results: The de novo bone formation was significantly higher in the AB group in comparison to the xenogeneic groups (p < 0.05). After 30 days, EB showed significantly (p < 0.05) more newly formed bone compared to the BB group. The soft tissue formation was significantly higher in the BB and EB group. Defects augmented with BB showed significantly (p < 0.05) higher portions of bone substitute materials compared to sides augmented with EB after 30 days., Conclusion: In the extra-oral model, AB blocks were superior concerning de novo bone formation. No clinical advantages of EB blocks could be observed., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The majority of patients diagnosed with osteomyelitis of the jaw have severe complaints. Unfortunately, the pathogenesis still remains unclear. Human ß-defensins expressed in epithelial and bone tissues as a part of the innate immunity may be involved in disease development. In this study, we hypothesize that expression levels of human ß-defensin-1 and -2 in the acute and secondary chronic osteomyelitis may be altered in comparison with healthy bone and with bisphosphonate-associated necrosis as well as irradiation from a previous study., Methods: Bone samples were collected during surgical debridement in a total of eight patients suffering from acute or secondary chronic osteomyelitis of the jaw. Expression levels of hBD-1 and -2 were quantified and related to non-stained cells. Ratios were compared by one-way ANOVA and multiple tests by Holm-Bonferroni., Results: Multiple testing revealed no significant differences for expression levels of human ß-defensin-1 between all groups, whereas labeling index of human ß-defensin-2 was significantly different between specimens of bisphosphonate-associated osteonecrosis of the jaws and all other groups. No significant difference occurred between samples of floride osteomyelitis and healthy bone for expression of hBD-1 and -2., Conclusions: Although the affected patients showed all clinical signs of acute inflammation, expression levels in acute and secondary chronic osteomyelitis in the jaws did not reveal statistically significant differences compared with healthy bone samples. The weak immunological host response in terms of a putative genetically predisposition should be further discussed as pathogenesis factor for osteomyelitis in the future., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, it must undergo rigorous testing. To correctly interpret the results of studies on implant material osseointegration, it is necessary to have a sound understanding of all the testing methods. The aim of this overview is to elucidate the methods that are used for the experimental evaluation of the osseointegration of implant materials., Discussion: In recent decades, there has been a constant proliferation of new materials and surface modifications in the field of dental implants. This continuous development of innovative biomaterials requires a precise and detailed evaluation in terms of biocompatibility and implant healing before clinical use. The current gold standard is in vivo animal testing on well validated animal models. However, long-term outcome studies on patients have to follow to finally validate and show patient benefit., Conclusion: No experimental set-up can provide answers for all possible research questions. However, a certain transferability of the results to humans might be possible if the experimental set-up is carefully chosen for the aspects and questions being investigated. To enhance the implant survival rate in the rising number of patients with chronic diseases which compromise wound healing and osseointegration, dental implant research on compromised animal models will further gain importance in future.

Aim: This study aimed to evaluate the healing of peri-implant defects grafted with microparticles (MPs)., Material and Methods: Six domestic pigs received nine standardized defects at the calvaria, and an implant was inserted in the middle of each defect. The space between the implant and lateral bone portion was filled with MP pellets (n = 18) or MP supernatant (n = 18) or left unfilled (n = 18). After 14 and 28 days, three animals were sacrificed and specimens removed for further processing. Samples were microradiographically and histologically analysed. In addition, we immunohistochemically stained for anti-vWF as a marker of angiogenesis., Results: In the case of bone regeneration and vessel formation, the null hypothesis can be partially rejected. After 14 and 28 days, no significant difference was observed within groups regarding de novo bone formation, bone density and osseointegration. However, superior vessel formation was found at both time points., Conclusion: Microparticles represent a promising treatment option to accelerate peri-implant vessel formation. Further studies are needed to investigate the regenerative properties of MPs more precisely., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: The aim of study paper is to present an overview of osseointegration of dental implants, focusing on tissue response, surface modifications and future perspective., Discussion: Great progress has been made over the decades in the understanding of osseous peri-implant healing of dental implants, leading to the development of new implant materials and surfaces. However, failures and losses of implants are an indicator that there is room for improvement. Of particular importance is the understanding of the biological interaction between the implant and its surrounding bone., Conclusion: The survival rates of dental implants in bone of over 90 % after 10 years show that they are an effective and well-established therapy option. However, new implant materials and surface modifications may be able to improve osseointegration of medical implants especially when the wound healing is compromised. Advanced techniques of evaluation are necessary to understand and validate osseointegration in these cases. An overview regarding the current state of the art in experimental evaluation of osseointegration of implants and implant material modifications will be given in Part II.

Nanoscale surface modification of biomedical implant materials offers enhanced biological activity concerning protein adsorption and cell adherence. Nanoporous anodic alumina oxide (AAO) layers were prepared by electrochemical oxidation of thin Al-seed layers in 0.22 M C2H2O4, applying anodization voltages of 20-60 V. The AAO layers are characterized by a mean pore diameter varying from 15 to 40 nm, a mean pore distance of 40-130 nm, a total porosity of ≈ 10% and a thickness of 560 ± 40 nm. Zeta potential and isoelectric point (iep) were derived from streaming potential measurements and correlated to the topology variation of the nanoporous AAO layers. With decreasing pore diameter a shift of iep from ≈ 7.9 (pore diameter 40 nm) to ≈ 6.7 (pore diameter 15 nm) was observed. Plain alumina layers, however, possess an iep of ≈ 9. Compared to the plain alumina surface an enhanced adherence and activity of hFOB cells was observed on the nanoporous AAO after 24h culture with a maximum at a pore size of 40 nm. The topology-induced change of the electrochemical surface state may have a strong impact on protein adsorption as well as on cell adhesion, which offers a high potential for the development of bioactive AAO coatings on various biomaterial substrates., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Aim: Diabetes mellitus is classified as a relative contraindication for implant treatment, and higher failure rates have been seen in diabetic patients. The aim of the present study was to investigate the effect of diabetes on peri-implant bone formation in an animal model of human bone repair., Materials and Methods: Diabetes was induced by an intra-venous application of streptozotocin (90 mg/kg) in 15 domestic pigs. Implants were placed after significant histopathological changes in the hard and soft tissues were verified. The bone-implant contact (BIC), peri-implant bone mineral density (BMD), and expression of collagen type-I and osteocalcin proteins were qualitatively evaluated 4 and 12 weeks after implantation. Fifteen animals served as healthy controls., Results: Diabetes caused pathological changes in the soft and hard tissues. The BIC and BMD were significantly reduced in the diabetic group after 4 and 12 weeks. Collagen type-I was increased in the diabetic group at both time points, whereas osteocalcin was reduced in the diabetic group., Conclusions: Poorly controlled diabetes negatively affects peri-implant bone formation and bone mineralization. These findings have to be taken into consideration for diabetic patients with an indication for implant therapy., (© 2011 John Wiley & Sons A/S.)

Unlabelled: The feasibility of postproduction neutron activation of an enteric-coated pancreatic enzyme preparation for in vivo gastric emptying studies has been investigated., Methods: During production of this multicomponent preparation, small amounts of 170Er-enriched erbium oxide, suitable for neutron activation, were added., Results: Postproduction neutron irradiation of the labeled preparation resulted in short-lived (7.5 hr) gamma-emitting 171Er. Various radiocontaminants, however, are produced also. Because of variations in activation yields, half-lives, decay schemes and radiotoxicities, both major and trace constituents were considered for optimization of both dosimetry and the diagnostic measurement. Conditions were optimized for the best ratio of the committed dose equivalent due to 171Er to the total committed dose equivalent., Conclusion: The results show that postproduction neutron activation of a 170Er-enriched multicomponent preparation can be performed safely within the guidelines set by the WHO for experiments in humans involving radioactive materials.

Besides the characterization of the active ingredient 4-amino-6-methoxy-1-phenmyl-pyridazinium methyl sulfate (ameziuniummetilsulfate, LU 1631, Regulton) the formulation and process development for tablets containing 10 mg active substance are described. The mixing behaviour of the ingredients and the compressing properties of the resulting directly compressible mixture are elucidated so that a reliable and reproducible manufacturing process is ensured. The quality of the active substance and tablet is described in detail and the stability for up to five years is demonstrated. The analytical specifications used are given.