Suitability of R. pulmo Jellyfish-Collagen-Coated Well Plates for Cytocompatibility Analyses of Biomaterials.

Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/-12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.

New and innovative biomaterials, techniques and therapy concepts: Biologization in maxillofacial surgery, oral surgery and dentistry is in full swing. PRF, PRGF, PRP, blood plasma-stabilized augmentations, supplementation of micronutrients and vitamins - what opportunities do such "biological" approaches actually offer? We introduce them here.

Biomaterials of natural origin have recently gained increasing attention in the field of dental implantology. The requirements for such materials, however, are very high. In addition to high clinical efficiency in tissue regeneration, wound healing should be demonstrably positively influenced. The translational division for regenerative orofacial medicine of the Clinic and Polyclinic for Oral and Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf (UKE) is examining this research topic by investigating which innovative treatment methods for the reconstruction of bone defects or for augmentative procedures can be applied in the future or are already being applied in the field of oral and maxillofacial surgery.

Evaluation of a program for routine implementation of shared decision-making in cancer care: results of a stepped wedge cluster randomized trial.

BACKGROUND: Shared decision-making (SDM) is preferred by many patients in cancer care. However, despite scientific evidence and promotion by health policy makers, SDM implementation in routine health care lags behind. This study aimed to evaluate an empirically and theoretically grounded implementation program for SDM in cancer care. METHODS: In a stepped wedge design, three departments of a comprehensive cancer center sequentially received the implementation program in a randomized order. It included six components: training for health care professionals (HCPs), individual coaching for physicians, patient activation intervention, patient information material/decision aids, revision of quality management documents, and reflection on multidisciplinary team meetings (MDTMs). Outcome evaluation comprised four measurement waves. The primary endpoint was patient-reported SDM uptake using the 9-item Shared Decision Making Questionnaire. Several secondary implementation outcomes were assessed. A mixed-methods process evaluation was conducted to evaluate reach and fidelity. Data were analyzed using mixed linear models, qualitative content analysis, and descriptive statistics. RESULTS: A total of 2,128 patient questionnaires, 559 questionnaires from 408 HCPs, 132 audio recordings of clinical encounters, and 842 case discussions from 66 MDTMs were evaluated. There was no statistically significant improvement in the primary endpoint SDM uptake. Patients in the intervention condition were more likely to experience shared or patient-lead decision-making than in the control condition (d=0.24). HCPs in the intervention condition reported more knowledge about SDM than in the control condition (d = 0.50). In MDTMs the quality of psycho-social information was lower in the intervention than in the control condition (d = - 0.48). Further secondary outcomes did not differ statistically significantly between conditions. All components were implemented in all departments, but reach was limited (e.g., training of 44% of eligible HCPs) and several adaptations occurred (e.g., reduced dose of coaching). CONCLUSIONS: The process evaluation provides possible explanations for the lack of statistically significant effects in the primary and most of the secondary outcomes. Low reach and adaptations, particularly in dose, may explain the results. Other or more intensive approaches are needed for successful department-wide implementation of SDM in routine cancer care. Further research is needed to understand factors influencing implementation of SDM in cancer care. TRIAL REGISTRATION: clinicaltrials.gov, NCT03393351 , registered 8 January 2018.

In vitro Activity of Antimicrobial Wound Dressings on P. aeruginosa Wound Biofilm.

The treatment of acute and chronic infected wounds with residing biofilm still poses a major challenge in medical care. Interactions of antimicrobial dressings with bacterial load, biofilm matrix and the overall protein-rich wound microenvironment remain insufficiently studied. This analysis aimed to extend the investigation on the efficacy of a variety of antimicrobial dressings using an in vitro biofilm model (lhBIOM) mimicking the specific biofilm-environment in human wounds. Four wound dressings containing polyhexanide (PHMB), octendine di-hydrochloride (OCT), cadexomer-iodine (C-IOD) or ionic silver (AG) were compared regarding their antimicrobial efficacy. Quantitative analysis was performed using a quantitative suspension method, separately assessing remaining microbial counts within the solid biofilm as well as the dressing eluate (representing the absorbed wound exudate). Dressing performance was tested against P. aeruginosa biofilms over the course of 6 days. Scanning electron microscopy (SEM) was used to obtain qualitative visualization on changes in biofilm structure. C-IOD demonstrated superior bacterial reduction. In comparison it was the only dressing achieving a significant reduction of more than 7 log10 steps within 3 days. Neither the OCT- nor the AG-containing dressing exerted a distinct and sustained antimicrobial effect. PHMB achieved a non-significant microbicidal effect (1.71 ± 0.31 log10 steps) at day 1. Over the remaining course (6 days) it demonstrated a significant microbistatic effect compared to OCT, AG and the control. Quantitative results in the dressing eluate correlate with those of the solid biofilm model. Overall, AG- and OCT-containing dressings did not achieve the expected anti-biofilm efficacy, while C-IOD performed best. Chemical interaction with the biofilms extrapolymeric substance (EPS), visualized in the SEM, and dressing configuration (agent concentration and release pattern) are suspected to be responsible. The unexpected low and diverse results of the tested antimicrobial dressings indicate a necessity to rethink non-debridement anti-biofilm therapy. Focussing on the combination of biofilm-disruptive (for EPS structure) and antimicrobial (for residing microorganisms) features, as with C-IOD, using dehydration and iodine, appears reasonably complementary and an optimal solution, as suggested by the here presented in vitro data.

The Influence of Local Pamidronate Application on Alveolar Dimensional Preservation after Tooth Extraction-An Animal Experimental Study.

The aim of this randomized, controlled animal exploratory trial was to investigate the influence of local application of aminobisphosphonate pamidronate during the socket preservation procedure. Mandibular premolars were extracted in five Göttingen minipigs. Two animals underwent socket preservation using BEGO OSS (n = 8 sockets) and three animals using BEGO OSS + Pamifos (15 mg) (n = 12 sockets). After jaw impression, cast models (baseline, eight weeks postoperative) were digitized using an inLab X5 scanner (Dentsply Sirona) and the generated STL data were superimposed and analyzed with GOM Inspect 2018 (GOM, Braunschweig). After 16 weeks, the lower jaws were prepared and examined using standard histological methods. In the test group (BEGO OSS + pamidronate), buccooral dimensional loss was significantly lower, both vestibulary (0.80 ± 0.57 mm vs. 1.92 ± 0.63 mm; p = 0.00298) and lingually (1.36 ± 0.58 mm vs. 2.56 ± 0.65 mm; p = 0.00104) compared with the control group (BEGO OSS). The test group showed a significant difference between vestibular and lingual dimensional loss (p = 0.04036). Histology showed cortical and cancellous bone in the alveolar sockets without signs of local inflammation. Adjuvant application of pamidronate during socket preservation reduces alveolar dimensional loss significantly. Further investigations with regard to dose-response relationships, volume effects, side effects, and a verification of the suitability in combination with other bone substitute materials (BSMs) are necessary.

Evaluation of a program for routine implementation of shared decision-making in cancer care: study protocol of a stepped wedge cluster randomized trial.

BACKGROUND: Shared decision-making (SDM) has become increasingly important in health care. However, despite scientific evidence, effective implementation strategies, and a prominent position on the health policy agenda, SDM is not widely implemented in routine practice so far. Therefore, we developed a program for routine implementation of SDM in oncology by conducting an analysis of the current state and a needs assessment in a pilot study based on the Consolidated Framework for Implementation Research (CFIR). Based on these results, the main aim of our current study is to evaluate the process and outcome of this theoretically and empirically grounded multicomponent implementation program designed to foster SDM in routine cancer care. METHODS: We use a stepped wedge design, a variant of the cluster randomized controlled trial. The intervention to be implemented is SDM. Three participating clinics of one comprehensive cancer center will be randomized and receive the multicomponent SDM implementation program in a time-delayed sequence. The program consists of the following strategies: (a) SDM training for health care professionals, (b) individual coaching for physicians, (c) patient activation strategy, (d) provision of patient information material and decision aids, (e) revision of the clinics' quality management documents, and (f) critical reflection of current organization of multidisciplinary team meetings. We will conduct a mixed methods outcome and process evaluation. The outcome evaluation will consist of four measurement points. The primary outcome is adoption of SDM, measured by the 9-item Shared Decision Making Questionnaire. A range of other implementation outcomes will be assessed (i.e., acceptability, readiness for implementing change, appropriateness, penetration). The implementation process will be evaluated using stakeholder interviews and field notes. This will allow adapting interventions if necessary. DISCUSSION: This study is the first large study on routine implementation of SDM conducted in German cancer care. We expect to foster implementation of SDM at the enrolled clinics. Insights gained from this study, using a theoretically and empirically grounded approach, can inform other SDM implementation studies and health policy developments, both nationally and internationally. TRIAL REGISTRATION: clinicaltrials.gov, NCT03393351 . Registered 8 January 2018.

Applications of Metals for Bone Regeneration.

The regeneration of bone tissue is the main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, as well as resorb in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated, where it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between new bone tissue formation and material degradation has not been found, until now. The addition of different substances such as collagen or growth factors and also of different cell types has already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are used differently as a basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue, playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designed for bone regeneration, with the aim to provide an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

Postoperative bleeding risk for oral surgery under continued rivaroxaban anticoagulant therapy.

OBJECTIVES: The purpose of this study was to assess the risk of postoperative bleeding complications after oral procedures performed under continued mono or dual anticoagulation therapy with rivaroxaban (and aspirin). METHODS: This retrospective single-center observational study included 52 oral procedures performed under continued oral anticoagulant therapy with rivaroxaban (20 mg/day). Among them, two procedures were performed under continued dual therapy with aspirin (100 mg/day) added to the regimen. Postoperative bleeding events were compared with 285 oral procedures in patients without any anticoagulation/antiplatelet therapy. RESULTS: Postoperative bleeding complications after oral surgery occurred significantly more often in patients under continued rivaroxaban therapy (11.5 %) than in the control cases without anticoagulation/antiplatelet medication (0.7 %). All of the bleeding events were manageable: Two of them were treated with local compression, three by applying new fibrin glue with (one case) or without (two cases) secondary sutures, one occurred during a weekend and was therefore treated under inpatient conditions with suture replacement. All postoperative bleeding episodes occurred during the first postoperative week. CONCLUSIONS: According to our data, continued anticoagulation therapy with rivaroxaban significantly increases postoperative bleeding risk for oral surgical procedures, although the bleeding events were manageable. CLINICAL RELEVANCE: Oral surgeons, cardiologists, general physicians, and patients should be aware of the increased bleeding risk after oral surgical procedures. Close observation up to 1 week postoperatively is advisable to prevent excessive bleeding.

Optimized in vitro procedure for assessing the cytocompatibility of magnesium-based biomaterials.

Magnesium (Mg) is a promising biomaterial for degradable implant applications that has been extensively studied in vitro and in vivo in recent years. In this study, we developed a procedure that allows an optimized and uniform in vitro assessment of the cytocompatibility of Mg-based materials while respecting the standard protocol DIN EN ISO 10993-5:2009. The mouse fibroblast line L-929 was chosen as the preferred assay cell line and MEM supplemented with 10% FCS, penicillin/streptomycin and 4mM l-glutamine as the favored assay medium. The procedure consists of (1) an indirect assessment of effects of soluble Mg corrosion products in material extracts and (2) a direct assessment of the surface compatibility in terms of cell attachment and cytotoxicity originating from active corrosion processes. The indirect assessment allows the quantification of cell-proliferation (BrdU-assay), viability (XTT-assay) as well as cytotoxicity (LDH-assay) of the mouse fibroblasts incubated with material extracts. Direct assessment visualizes cells attached to the test materials by means of live-dead staining. The colorimetric assays and the visual evaluation complement each other and the combination of both provides an optimized and simple procedure for assessing the cytocompatibility of Mg-based biomaterials in vitro.

Does pulsed magnetic field therapy influence nerve regeneration in the median nerve model of the rat?

The aim of this study was to evaluate the impact of pulsed magnetic field therapy on peripheral nerve regeneration after median nerve injury and primary coaptation in the rat. Both median nerves were surgically exposed and denervated in 24 female Wistar rats. A microsurgical coaptation was performed on the right side, whereas on the left side a spontaneous healing was prevented. The study group underwent a daily pulsed magnetic field therapy; the other group served as a control group. The grasping force was recorded 2 weeks after the surgical intervention for a period of 12 weeks. The right median nerve was excised and histologically examined. The histomorphometric data and the functional assessments were analyzed by t-test statistics and one-way ANOVA. One-way ANOVA indicated a statistically significant influence of group affiliation and grasping force (P = 0.0078). Grasping strength was higher on a significant level in the experimental group compared to the control group permanently from the 9th week to the end of the study. T-test statistics revealed a significantly higher weight of the flexor digitorum sublimis muscle (P = 0.0385) in the experimental group. The histological evaluation did not reveal any statistically significant differences concerning the histomorphometric parameters. Our results suggest that the pulsed magnetic field therapy has a positive influence on the functional aspects of neural regeneration. More studies are needed to precisely evaluate and optimize the intensity and duration of the application.

Apicoectomy using Er:YAG laser in association with microscope: a comparative retrospective investigation.

OBJECTIVE: This retrospective clinical investigation intends to examine the effectiveness of an Er:YAG laser used in conjunction with a dental operation microscope for apicoectomy, in comparison with the traditional surgical procedure. BACKGROUND DATA: The Er-YAG laser has shown great potential in application to periapical surgery; however, clinical data are rare. METHODS: To this end, 78 patients who had undergone apicoectomy in a private dental office were selected; 41 patients were treated by the traditional surgical technique for apicoectomy and 37 patients were treated using an Er:YAG laser under microscopic control. The five cardinal symptoms of inflammation were taken as clinical parameters/examination criteria and evaluated after postoperative days 1, 7, and 180, where days 7 and 180 after the operation can be regarded as the customary times for follow-up controls at the private dental office. RESULTS: Microscopically guided, laser-assisted treatment seems to favor a better healing process overall. After the first postoperative day, redness and swelling of the operation area were significantly reduced (p<0.001 and p=0.0048). Seven days after the operation, all inflammation parameters were statistically significantly lower in the laser-treated group (p<0.05). On day 180, 6 out of 41 patients in the control group still displayed a disturbed function of the treated teeth, whereas none of the patients in the laser group experienced further complaints. CONCLUSIONS: As a result, it can be ascertained that the use of an Er:YAG laser as an adjuvant tool in periapical surgery, with additional control by an operation microscope, displays significantly better results in terms of postoperative healing, in comparison with the conventional surgical treatment of apicoectomy.

Clinical evaluation of a biphasic calcium composite grafting material in the treatment of human periodontal intrabony defects: a 12-month randomized controlled clinical trial.

BACKGROUND: The aim of this study was to compare the clinical outcome of a novel biphasic calcium composite (BCC) biomaterial versus autogenous bone spongiosa (ABS) or open flap debridement (OFD) for the treatment of intrabony periodontal defects. METHODS: Forty-five subjects with at least one intrabony defect with a probing depth (PD) >or=7 mm and a vertical radiographic bone loss >or=3 mm were enrolled in the study. Subjects were randomly assigned to treatment with BCC (n = 15), ABS (n = 15), or OFD (n = 15). Clinical parameters were recorded at baseline and 12 months after surgery and included the plaque index, gingival index, PD, clinical attachment level (CAL), and gingival recession. RESULTS: In all treatment groups, significant PD reductions and CAL gains occurred during the study period (P <0.0001). At 12 months, patients treated with BCC exhibited a mean PD reduction of 3.6 +/- 0.7 mm and a mean CAL gain of 3.0 +/- 0.8 mm compared to baseline. Corresponding values for patients treated with ABS were 3.4 +/- 0.8 mm and 2.9 +/- 0.9 mm, whereas OFD sites produced values of 2.8 +/- 0.8 mm and 1.6 +/- 0.7 mm. Compared to OFD, the additional CAL gain was significantly greater in patients treated with BCC (P = 0.002) and ABS (P = 0.001). The additional PD reduction was significant for the BCC group (P = 0.011) and borderline significant for the ABS group (P = 0.059). There were no significant differences of PD and CAL changes between BCC and ABS groups. CONCLUSIONS: The clinical benefits of BCC were equivalent to ABS and superior to OFD alone. BCC may be an appropriate alternative to conventional graft materials.