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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., (© 2022. The Author(s).)

Purpose: Allogeneic cortical bone plates (CP) might be used for alveolar ridge augmentation as an alternative to autogenous grafts (AG) and bone substitutes (BS). We report about a multicenter case series and our experiences of more than 300 cases using CP and the shell technique for reconstruction of the alveolar process to illustrate surgical key steps, variations, and complication management., Methods: Different types of alveolar ridge defects were augmented using the shell technique via CP. The space between the CP and the alveolar bone was filled with either autogenous or allogeneic granules (AUG, ALG) or a mixture of both. Implants were placed after 4-6 months. Microscopic and histological assessments were performed. In addition, space filling using AUG, ALG and bovine BS was discussed., Results: Scanning electron microscopy demonstrated the compact cortical structure of CP and the porous structure of ALG allowing micro-vessel ingrowth and bone remodeling. Histological assessment demonstrated sufficient bone remodeling and graft resorption after 4-6 months. In total, 372 CP cases and 656 implants were included to data analysis. The mean follow-up period was about 3.5 years. Four implants failed, while all implant failures were caused by peri-implantitis. Next, 30 CP complications were seen, while in 26 CP complications implant placement was possible. CP rehydration, stable positioning by adjusting screws, smoothing of sharp edges, and a tension-free wound closure were identified as relevant success factors. Space filling using ALG and a mixture of AUG/ALG resulted in sufficient bone remodeling, graft resorption and stability of the augmented bone., Conclusions: CP and the shell technique is appropriate for alveolar ridge augmentation with adequate bone remodeling and low complication rates. Allografts can prevent donor site morbidity and therefore may decrease discomfort for the patient., (© 2022. The Author(s).)

Introduction: Throat packs (TP) are used in upper airway surgery to avoid accumulation and aspiration of blood, foreign bodies, and fluids. But side effects such as sore throat and TP retention have been reported and challenge the standardized use of TP. The aim of this study is to compare benefits and side effects of TP versus no TP for upper airway procedures in intubation anesthesia., Material and Methods: One hundred forty-eight patients with surgical interventions at the upper airway under intubation anesthesia were included. Of those, n = 74 each were treated without (A, control) and with (B) TP. Study group B was subdivided whether TP was placed by the surgeon (B1; n = 37) or by the anesthesiologist (B2; n = 37). TP-related side effects such as sore throat, foreign body sensation, hoarseness, dyspnea, difficulty of swallowing, nausea, retching, nausea, aspiration, and pneumonia as well as the influence of TP design and the applicant (surgeon or anesthetist) were analyzed., Results: A significantly increased rate of difficulty of swallowing (p = 0.045), intensity of sore throat (p = 0.04), and foreign body sensation (p = 0.024) was found in group B when compared to group A. There was no correlation between hoarseness, dyspnea, nausea, retching, and TP. No case of aspiration or pneumonia was seen but one TP was accidentally forgotten in the patient. B2 showed an increased frequency of difficulty swallowing, followed by A and B1. B1 led to the highest incidence of nausea followed by the A and B2., Conclusion: The use of TP led to a high rate of side effects without showing the propagated advantages., Clinical Relevance: The use of TP must be considered critically and cannot generally be recommended without specific reasons, such as high aspiration risk., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Complex, three-dimensional bony defects still represent challenging situations in routine implant dentistry. The aim of this study was to evaluate implant survival in customized bone regeneration using a patient-specific titanium mesh., Material and Methods: Patients (n = 21, implants 36) who had obtained an augmentation procedure with patient-specific titanium mesh were examined after 5.7 ± 0.38 years. Survival rate, clinical parameters for periimplantitis (Bleeding on Probing [BOP] and suppuration), and radiographic examination were evaluated. Peri-implant marginal bone loss (MBL) was calculated by using an image assessment program. Additionally, the influence of various factors on treatment outcomes such as periodontitis, smoking, professional maintenance, or diabetes was assessed as well as the impact on quality of life applying the Oral Health Impact Profile (OHIP)., Results: The implant survival rate was 97%, with one implant loss in the lower jaw. At the end of the observation period, MBL showed mesial 0.13 ± 1.84 mm and distal -0.13 ± 1.73 mm. The lower jaw showed significant more MBL mesial compared with the upper jaw (p = .034, cluster-adjusted). Periodontitis was significantly associated with MBL mesial and distal (p < .05). Positive BOP (four implants) was significantly associated with MBL mesial (p = .0031) and distal (p = .0018). MBL was significantly associated with suppuration mesial (p < .0001) and distal (p < .0001)., Conclusions: CBR® results in high implant survival rate and stabilized augmented marginal bone after follow-up of minimum 5 years. Periodontitis seems to play the mayor role for long-term stability indicated by BOP and suppuration., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Various local and systemic factors compromise oral wound healing and may lead to wound dehiscence, inflammation, or ulcers. Currently, there is a lack of topical therapeutical options. Thus, this study aimed to investigate the effect of Aloe vera (AV) and Rheum palmatum root (RPR) on oral wound healing capacity in vitro. The effect of AV and RPR on human primary fibroblast viability and migration was studied by measuring metabolic activity and gap closure in a scratch assay. Furthermore, cell cycle distribution and cytoskeletal features were analyzed. Antimicrobial activity against the oral pathogen Porphyromonas gingivalis was evaluated by broth microdilution assay. AV and RPR increased fibroblast migration after single agent treatment. Synergistic effects of the plant extract combination were observed regarding cellular migration which were confirmed by calculation of the phenomenological combination index (pCI), whereas the cell cycle distribution was not influenced. Furthermore, the combination of AV and RPR showed synergistic antibacterial effects as determined by the fractional inhibitory concentration index. This study demonstrated that the combination of AV and RPR can promote the migration of human primary fibroblasts in vitro and exert antimicrobial efficacy against P. gingivalis , suggesting these compounds for the topical treatment of wound healing disorders.

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has been considered an important strategy for cancer therapy. VEGFR2 inhibitors targeting tumor angiogenic pathways have been widely used in clinical cancer treatment. However, inherent or acquired resistance to anti-angiogenic drugs may occur and thus limit their clinical application. New VEGFR2 inhibitors are still highly demanded. The aim of this study was to investigate VEGFR2-targeted artemisinin (ARS)-type compounds for cancer treatment. Here, we reported the ARS derivative FO-ARS-123 as a novel VEGFR2 inhibitor, which displayed potent binding activity with VEGFR2 in in silico by molecular docking (pKi, 0.40 ± 0.31 nM) and in vitro by microscale thermophoresis (Kd, 1.325 ± 0.055 μM). In addition, compound FO-ARS-123 displayed a strong inhibition on cell proliferation of a broad range of cancer cells as well as suppressed cell migration and invasion. Remarkably, FO-ARS-123 exerted profound anti-angiogenesis effects in the in vitro tube formation assay and in vivo CAM assay. These results suggest that FO-ARS-123 might be a novel and promising anti-angiogenesis agent for cancer treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Efferth discloses the patents US2006084675 and ES200401396, which are related to Artemisia annua, artemisinin and derivatives, but not in the context of the present investigation. Edmond Fleischer is the holder of Fleischer-Consult and is an employee of Fischer Analytics (Weiler, Germany).The other authors have no potential competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The vascular endothelial growth factor receptor 2 (VEGFR2) is widely recognized as a key effector in angiogenesis and cancer progression and has been considered a critical target for the development of anti-cancer drugs. Artemisinin (ARS) and its derivatives exert profound efficacy in treating not only malaria but also cancer. As a novel ARS-type compound, FO8643 caused significant suppression of the growth of a panel of cancer cells, including both solid and hematologic malignancies. In CCRF-CEM leukemia cells, FO8643 dramatically inhibited cell proliferation coupled with increased apoptosis and cell cycle arrest. Additionally, FO8643 restrained cell migration in the 2D wound healing assay as well as in a 3D spheroid model of human hepatocellular carcinoma HUH-7 cells. Importantly, SwissTargetPrediction predicted VEGFR2 as an underlying target for FO8643. Molecular docking simulation further indicated that FO8643 formed hydrogen bonds and hydrophobic interactions within the VEGFR2 kinase domain. Moreover, FO8643 directly inhibited VEGFR2 kinase activity and its downstream action including MAPK and PI3K/Akt signaling pathways in HUH-7 cells. Encouragingly, FO8643 decreased angiogenesis in the chorioallantoic membrane assay in vivo. Collectively, FO8643 is a novel ARS-type compound exerting potential VEGFR2 inhibition. FO8643 may be a viable drug candidate in cancer therapy., (Copyright © 2022. Published by Elsevier B.V.)

To reduce microvascular free flap failure (MFF), monitoring is crucial for the early detection of malperfusion and allows timely salvage. Therefore, the aim of this study was to evaluate hyperspectral imaging (HSI) in comparison to micro-Doppler sonography (MDS) to monitor MFF perfusion in an in vivo rodent model. Bilateral groin flaps were raised on 20 Sprague−Dawley rats. The femoral artery was transected on the trial side and re-anastomosed. Flaps and anastomoses were assessed before, during, and after the period of ischemia every ten minutes for overall 60 min using HSI and MDS. The contralateral sides’ flaps served as controls. Tissue-oxygenation saturation (StO2), near-infrared perfusion index (NPI), hemoglobin (THI), and water distribution (TWI) were assessed by HSI, while blood flow was assessed by MDS. HSI correlates with the MDS signal in the case of sufficient and completely interrupted perfusion. HSI was able to validly and reproducibly detect tissue perfusion status using StO2 and NPI. After 40 min, flap perfusion decreased due to the general aggravation of hemodynamic circulatory situation, which resulted in a significant drop of StO2 (p < 0.005) and NPI (p < 0.005), whereas the Doppler signal remained unchanged. In accordance, HSI might be suitable to detect MFF general complications in an early stage and further decrease MFF failure rates, whereas MDS may only be used for direct complications at the anastomose site.

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., (© 2022. The Author(s).)

This clinical prospective randomized controlled study aimed to investigate the differences between Radial (RFFF) and Ulnar (UFFF) Forearm Free Flap in terms of success, performance, and donor site morbidity. Thirty patients with reconstruction of the head and neck region were included. For the first time, this study assessed flap-perfusion characteristics, donor-site-wound-healing dynamics and hand perfusion using hyperspectral imaging. Further, subjective (Likert-scale, DASH-score) and objective (grip/pinch-strength) parameters of donor site morbidity were analysed. Postoperative follow-up was performed until 6 months after index surgery. With 100% of patients, RFFF and UFFF were equally successful. Compared to surrounding reference, UFFF revealed significant lower tissue oxygenation saturation (StO 2 ) than RFFF. Compared with UFFF, blood flow in both the thenar and hypothenar region were significantly reduced 6 months following RFFF transfer. After four weeks, 27% more patients demonstrated impaired wound healing following RFFF transfer. After 6 months, epithelial-surface continuity was restored in all patients of both groups. After 6 months, overall rates of both subjective and objective donor site morbidity were comparable between RFFF and UFFF. RFFF and UFFF both demonstrate similar success rates and HSI-perfusion dynamics following transfer. After 4 weeks, wound-healing disorder appeared significantly more often in RFFF than in UFFF; however, they became equal after 6 months. RFFF and UFFF can be considered as mutual alternatives.

Background: Registration is most important in navigation-assisted-surgery including the matching between the coordinates of the actual patient space and the medical image. Marker-based techniques mostly include marker application with subsequent radiography. In the edentulous patient, maker-free methods are generally less accurate and reproducible. This new method of a marker-free registration uses the transverse palatal rugae as registration structures., Methods: (1) Segmentation of bone and hard palatal mucosa from initial 3D imaging (DICOM), (2) Maxillary intraoral-scan with transfer to the 3D imaging using an Iterative-Closest-Point-Algorithm (ICP), (3) Marking digital registration points with holes within IOS-stl, (4) Transformation of the spatially aligned IOS-stl to LabelMap and storage in DICOM (IOS-DICOM), (5) Alignment of DICOM and IOS-DICOM, (6) Controlled positioning of digital reg. points and clinical correlation., Results: Fiducial localization error (0.48 mm) and Target registration error (0.65 mm) is comparable to those of tooth-supported registration methods., Conclusion: This approach of marker-free registration for navigation-assisted-surgery could improve the treatment in edentulous patients avoiding additional imaging and invasive marker insertion., (© 2021 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons Ltd.)

Objectives: The aim of this study was to analyze the biomechanical characteristics of a novel cyanoacrylate-based tissue adhesive (CTA) for soft-tissue closure of the (non-) tooth-bearing alveolar process and around dental implants., Materials and Methods: Halves of porcine mandibles (n = 21) were randomly divided into three experimental intraoral wound closure groups (A-C) with three different mucoperiosteal flap types (F1-3, n = 7 each): F1, crestal incision between the last incisor and the canine with a mesial and distal vestibular relief; F2, crestal double-T-shaped incision and dental implant placement between the canine and the first premolar; and F3, trapezoidal incision on the second premolar. F1-3 were respectively closed using (A) monofil non-resorbable sutures, (B) CTA, and (C) a combination of both. Tensile strength (TS) and elasticity (E) measurements were performed for biomechanical analysis., Results: In F1, CTA showed a significantly reduced TS compared to A (p < 0.001) and C (p < 0.01). In F2, an increased TS of C compared to A (p < 0.01) and B (p < 0.001) was found. Here, E was significantly increased in C compared to B (p < 0.02). In F3, TS was significantly decreased in B compared to A (p < 0.01) and C (p < 0.001). The E in group C was significantly increased compared to B (p < 0.01)., Conclusions: Different biomechanical characteristics between CTA and sutures were found. CTA could be a possible alternative to sutures for intraoral wound closure in special conditions., Clinical Relevance: A combination of both, suturing and CTA, could be a promising option in critical soft-tissue wounds requiring high functional stability and elasticity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study compared the osseointegration of acid-etched, ultrahydrophilic, micro- and nanostructured implant surfaces (ANU) with non-ultra-hydrophilic, microstructured (SA) and non-ultrahydrophilic, micro- and nanostructured implant surfaces (AN) in vivo. Fifty-four implants ( n = 18 per group) were bilaterally inserted into the proximal tibia of New Zealand rabbits ( n = 27). After 1, 2, and 4 weeks, bone-implant contact (BIC, %) in the cortical (cBIC) and spongious bone (sBIC), bone chamber ingrowth (BChI, %), and the supra-crestal, subperiosteal amount of newly formed bone, called percentage of linear bone fill (PLF, %), were analyzed. After one week, cBIC was significantly higher for AN and ANU when compared to SA ( p = 0.01 and p = 0.005). PLF was significantly increased for ANU when compared to AN and SA ( p = 0.022 and p = 0.025). After 2 weeks, cBIC was significantly higher in SA when compared to AN ( p = 0.039) and after 4 weeks, no significant differences in any of the measured parameters were found anymore. Ultrahydrophilic implants initially improved osseointegration when compared to their non-ultrahydrophilic counterparts. In accordance, ultrahydrophilic implants might be appropriate in cases with a necessity for an accelerated and improved osseointegration, such as in critical size alveolar defects or an affected bone turnover.

Purpose: Considering a high prevalence of congenital and especially acquired bleeding disorders, their heterogeneity and the multitude of possible treatments strategies, a review of the scientific data on this topic is needed to implement a treatment guide for healthcare professionals., Methods: A selective literature review was performed via PubMed for articles describing oral surgery / dental implant procedures in patients with congenital and acquired bleeding disorders. Out of the existing literature, potential treatment algorithms were extrapolated., Results: In order to assess the susceptibility to bleeding, risk stratification can be used for both congenital and acquired coagulation disorders. This risk stratification, together with an appropriate therapeutic pathway, allows for an adequate and individualized therapy for each patient. A central point is the close interdisciplinary cooperation with specialists. In addition to the discontinuation or replacement of existing treatment modalities, local hemostyptic measures are of primary importance. If local measures are not sufficient, systemically administered substances such as desmopressin and blood products have to be used., Conclusions: Despite the limited evidence, a treatment guide could be developed by means of this narrative review to improve safety for patients and practitioners. Prospective randomized controlled trials are needed to allow the implementation of official evidence-based guidelines., (© 2022. The Author(s).)

Purpose: The aim of this study was to systematically review the available evidence to evaluate the efficacy of vitamin D supplementation or vitamin D depletion on the osseointegration of implants in animals and humans., Methods: The focus questions addressed were "Do vitamin D deficient subjects treated with (dental) implants have an inferior osseointegration than subjects with adequate serum vitamin D level?" and "Do vitamin D supplemented subjects treated with (dental) implants have a superior osseointegration than subjects with adequate serum vitamin D level?" Humans and animals were considered as subjects in this study. Databases were searched from 1969 up to and including March 2021 using different combination of the following terms: "implant", "bone to implant contact", "vitamin D" and "osseointegration". Letters to the editor, historic reviews, commentaries and articles published in languages other than English and German were excluded. The pattern of the present systematic review was customize to primarily summarize the pertinent data., Results: Thirteen experimental studies with animals as subject, two clinical studies and three case reports, with humans as subjects, were included. The amount of inserted titanium implants ranged between 24 and 1740. Results from three animal studies showed that vitamin D deficiency has a negative effect on new bone formation and/or bone to implant contact (BIC). Eight animal studies showed that vitamin D supplementation has a enhancing effect on BIC and/or new bone formation around implants. Furthermore, enhancing the impact of vitamin D supplementation on the osseointegration of implants in subjects with diabetes mellitus, osteoporosis and chronic kidney disease (CKD) were assessed. Studies and case reports involving human subjects showed that patients with a low serum vitamin D level have a higher tendency to exhibit an early dental implant failure. When supplemented with vitamin D the osseointegration was successful in the case reports and a beneficial impact on the changes in the bone level during the osseointegration were determined., Conclusions: Vitamin D deficiency seems to have a negative effect on the osseointegration of implants in animals. The supplementation of vitamin D appears to improve the osseointegration in animals with systemic diseases, such as vitamin D deficiency, diabetes mellitus, osteoporosis, and CKD. Slight evidence supports the hypothesis that humans similarly benefit from vitamin D supplementation in terms of osseointegration. Further investigation is required to maintain these assumptions., (© 2022. The Author(s).)

Oral mucosa is used in various surgical fields as a graft for the reconstruction of tissue defects. Tissue engineering of oral mucosa equivalents using autologous cells represents a suitable less burdensome alternative. The survival of the multilayered epithelium is essential for the functionality of the tissues in vivo. To ensure its functionality after transplantation, mucosa equivalents in vitro were subjected to extracorporeal shock wave therapy (ESWT) to determine whether this treatment stimulated the formation and differentiation of the epithelium. Mucosa equivalents treated with ESWT were examined for cellular metabolic activity using AlamarBlue TM assay. The formation of vascular structures, basement membrane, and multilayered epithelium were examined using confocal fluorescence microscopy and immunohistochemistry. The potential ingrowth in vivo was simulated using the chorioallantoic membrane model (CAM assay) in ovo. ESWT on culture day 19 of oral mucosa equivalents resulted in slightly increased cellular metabolic activity. The in vitro development of basement membrane and multilayer epithelium was stimulated by ESWT. Additionally, in the CAM assay, ESWT led to a more pronounced multilayered epithelium. Thus, ESWT stimulated the formation of a more distinct and differentiated multilayered epithelium of oral mucosa equivalents in vitro and might increase the chance of efficient ingrowth, survival, and functionality of tissue equivalents in vivo.

Background: The aim of this study was to analyze possible interactions of different xenogeneic collagen membranes (CM) and platelet-rich fibrin (PRF). PH values were evaluated in the CM rehydration process with PRF, and their influence on angiogenesis was analyzed in vivo. Materials and Methods: Porcine (Bio-Gide®, Geistlich)- and bovine-derived collagen membranes (Symbios®, Dentsply Sirona) were biofunctionalized with PRF by plotting process. PRF in comparison to blood, saline and a puffer pH7 solution was analysed for pH-value changes in CM rehydration process in vitro. The yolk sac membrane (YSM) model was used to investigate pro-angiogenic effects of the combination of PRF and the respective CM in comparison to native pendant by vessel in-growth and branching points after 24, 48 and 72 h evaluated light-microscopically and by immunohistochemical staining (CD105, αSMA) in vivo. Results: Significantly higher pH values were found at all points in time in PRF alone and its combined variants with Bio-Gide® and Symbios® compared with pure native saline solution and pH 7 solution, as well as saline with Symbios® and Bio-Gide® (each p < 0.01). In the YSM, vessel number and branching points showed no significant differences at 24 and 48 h between all groups (each p > 0.05). For PRF alone, a significantly increased vessel number and branching points between 24 and 48 h (each p < 0.05) and between 24 and 72 h (each p < 0.05) was shown. After 72 h, CM in combination with PRF induced a statistically significant addition to vessels and branching points in comparison with native YSM (p < 0.01) but not vs. its native pendants (p > 0.05). Summary: PRF represents a promising alternative for CM rehydration to enhance CM vascularization.

(1) Background: Born out of necessity, the implementation of digital processes experienced significant increase during the COVID-19 pandemic. Here, telemedicine offered a bridge to care and now an opportunity to reinvent virtual and hybrid care models, with the goal of improved healthcare access, outcomes, and affordability. The aim of this monocentric prospective, randomized trial was to compare conventional to telephone follow-up after minor dentoalveolar surgery on the basis of special aftercare questionnaires. (2) Methods: Sixty patients who underwent dentoalveolar surgery under local anesthesia were randomly assigned to both groups. After an average of four days, either telephone follow-up (test) or conventional personal aftercare (control) was performed. Based on the questionnaire, the following subject areas were evaluated: symptoms, complications, satisfaction with practitioner, travel, and waiting time, as well as the preferred form of follow-up care. (3) Results: There was no statistically significant difference regarding frequency of symptoms or complication rate. Patients who were assigned to the test group showed a clear tendency to prefer telephone follow-up (83.3%) to conventional aftercare (16.7%, p = 0.047). (4) Conclusions: The data suggest high acceptance of telephone-only follow-up after dentoalveolar surgery. The implementation of telemedicine could be a time- and money-saving alternative for both patients and healthcare professionals and provide healthcare access regardless of time and space.

Background: Medication-related osteonecrosis (MRONJ) of the jaw is a severe and feared side effect of antiresorptive therapy in the oncological setting. With growing evidence that impaired angiogenesis may represent a key factor in pathogenesis, the aim of this study was to evaluate an autologous platelet concentrate as a possible additive in surgical therapy to optimize vascularization and, subsequently, resolution rates., Material and Methods: A non-interventional, prospective, multicenter study was conducted, and all patients with stage I-III MRONJ, undergoing antiresorptive therapy for an oncological indication, were included. The necrosis was treated surgically without (study arm A) or with (arm B) the addition of an autologous platelet concentrate (platelet-rich fibrin, PRF)., Results: After 5, 14, and 42 days postoperative, wound healing (primary outcome: mucosal integrity) as well as downstaging, pain perception, and oral health-related quality of life (secondary outcome) were assessed via clinical evaluation. Among the 52 patients included, primarily with MRONJ stage I and II, the use of PRF as an additive in surgical therapy did not display a significant advantage for wound healing ( p = 0.302), downstaging ( p = 0.9), pain reduction ( p = 0.169), or quality of life ( p = 0.9)., Summary: In conclusion, PRF as an adjunct did not significantly optimize wound healing. Further, no significant changes in terms of downstaging, pain sensation, and oral health-related quality of life were found.

Objectives: COVID-19 is considered one of the most serious pandemic in history and has posed major challenges to the world's health care. Dentistry and oral and maxillofacial surgery (CMFS) are particularly affected due to direct exposure to the respiratory tract, as the reservoir of SARS-CoV-2. In this study, the impact of the COVID-19-pandemic on a dental and CMFS emergency services in Germany in 2020 was first time investigated and correlated with governmental restriction measures in public life., Materials and Methods: Epidemiological data of a German University Hospital were analysed from a total of 8386 patients in 2019 and 2020. Parameters included information on demographics, time, weekday and reason for presentation, as well as diagnosis and therapy performed. Data from 2020 were compared with those from 2019, taking into account the nationwide periods of public life restrictions., Results: In 2020, 22% fewer patients presented via dental and CMFS emergency service. In a monthly comparison, there were negative peaks of up to - 41% in November, but also a plus of 26% in July. The largest decreases were recorded during the lockdown periods in spring (- 33%) and winter (- 39%). Further, a threefold increase in actual emergencies and inpatient admissions revealed during these time periods (p < 0.001)., Conclusions: COVID-19 pandemic had a significant impact on the dental and CMFS emergency service in 2020 resulting in more severe cases., Clinical Relevance: This study underlines the importance of maintaining an emergency service system and basic outpatient care in these specialities, which requires uniform recommendations from the medical-dental societies and politics., (© 2021. The Author(s).)

Background: The primary dentin, secondary dentin, and reactive tertiary dentin are formed by terminal differentiated odontoblasts, whereas atubular reparative tertiary dentin is formed by odontoblast-like cells. Odontoblast-like cells differentiate from pulpal stem cells, which express the neural stem cell markers nestin, S100β, Sox10, and P0. The denticle (pulp stone) is an unique mineralized extracellular matrix that frequently occurs in association with the neurovascular structures in the dental pulp. However, to date, the cellular origin of denticles in human dental pulp is unclear. In addition, the non-collagenous extracellular dentin matrix proteins dentin matrix protein 1 (DMP1), dentin sialoprotein (DSP), and dentin phosphoprotein (DPP) have been well characterized in the dentin matrix, whereas their role in the formation and mineralization of the denticle matrix remains to be clarified., Methods: To characterize the formation of denticle, healthy human third molars (n = 59) were completely sectioned and evaluated by HE staining in different layers at 720 µm intervals. From these samples, molars with (n = 5) and without denticles (n = 8) were selected. Using consecutive cryo-sections from a layer containing denticles of different sizes, we examined DMP1, DSP, and DPP in denticle lining cells and tested their co-localizations with the glial stem cell markers nestin, S100β, Sox10, and P0 by quantitative and double staining methods., Results: DMP1, DSP and DPP were found in odontoblasts, whereas denticle lining cells were positive only for DMP1 and DSP but not for DPP. Nestin was detected in both odontoblasts and denticle lining cells. S100β, Sox10, and P0 were co-localized with DMP1 and DSP in different subpopulations of denticle lining cells., Conclusions: The co-localization of S100β, Sox10, and P0 with DMP1 and DSP in denticle lining cells suggest that denticle lining cells are originated from glial and/or endoneurial mesenchymal stem cells which are involved in biomineralization of denticle matrix by secretion of DMP1 and DSP. Since denticles are atubular compared to primary, secondary, reactionary tertiary dentin and denticle formed by odontoblasts, our results suggest that DPP could be one of the proteins involved in the complex regulation of dentinal tubule formation., Competing Interests: Conflict of Interests Authors declare no conflict of interest., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

(1) Background: Immediate dental implant placement has been a subject of great interest over the last decade. Here, information regarding the anatomy and bone thickness of the jaw prior to dental implant placement is crucial to increase the surgery's success and the patient's safety. The clinical premises for this approach have been controversially discussed. One of those heavily discussed premises is a buccal bone thickness of at least 1 mm thickness. This meta-analysis aims to systematically review buccal bone thickness (BBT) in healthy patients. Thus, the feasibility of immediate dental implant placement in daily practice can be assessed. (2) Methods: A search in the electronic databases was performed to identify articles reporting on BBT that was measured by computed tomography in adults. (3) Results: We were able to find 45 studies, including 4324 patients with 25,452 analyzed teeth. The analysis showed a BBT at the alveolar crest of 0.76 ± 0.49 mm in the maxillary frontal and of 1.42 ± 0.74 mm in the maxillary posterior region. In the mandible, the average measured values were similar to those in the maxilla (front: 0.95 ± 0.58 mm; posterior: 1.20 ± 0.96 mm). In the maxillary frontal region 74.4% and in the mandibular frontal region 61.2% of the crestal buccal bones showed widths <1 mm. (4) Conclusions: In more than 60% of the cases, the BBT at the alveolar crest is <1 mm in maxillary and mandibular frontal regions. This anatomic data supports careful pre-surgical assessment, planning of a buccal graft, and critical selection of indication for immediate implant placement, especially in the maxillary and mandibular frontal and premolar region.

In reconstructive surgery, free flap failure, especially in complex osteocutaneous reconstructions, represents a significant clinical burden. Therefore, the aim of the presented study was to assess hyperspectral imaging (HSI) for monitoring of free flaps compared to clinical monitoring. In a prospective, non-randomized clinical study, patients with free flap reconstruction of the oro-maxillofacial-complex were included. Monitoring was assessed clinically and by using hyperspectral imaging (TIVITA™ Tissue-System, DiaspectiveVision GmbH, Pepelow, Germany) to determine tissue-oxygen-saturation [StO 2 ], near-infrared-perfusion-index [NPI], distribution of haemoglobin [THI] and water [TWI], and variance to an adjacent reference area (Δreference). A total of 54 primary and 11 secondary reconstructions were performed including fasciocutaneous and osteocutaneous flaps. Re-exploration was performed in 19 cases. A total of seven complete flap failures occurred, resulting in a 63% salvage rate. Mean time from flap inset to decision making for re-exploration based on clinical assessment was 23.1 ± 21.9 vs. 18.2 ± 19.4 h by the appearance of hyperspectral criteria indicating impaired perfusion (StO 2 ≤ 32% OR StO 2 Δreference > -38% OR NPI ≤ 32.9 OR NPIΔreference ≥ -13.4%) resulting in a difference of 4.8 ± 5 h ( p < 0.001). HSI seems able to detect perfusion compromise significantly earlier than clinical monitoring. These findings provide an interpretation aid for clinicians to simplify postoperative flap monitoring.

Due to the demographic change, medicine faces a growing demand for tissue engineering solutions and implants. Often, satisfying tissue regeneration is difficult to achieve especially when co-morbidities hamper the healing process. As a novel strategy, we propose the incorporation of zinc oxide nanoparticles (ZnO NPs) into biomaterials to improve tissue regeneration. Due to their wide range of biocompatibility and their antibacterial properties, ZnO NPs are already discussed for different medical applications. As there are versatile possibilities of modifying their form, size, and function, they are becoming increasingly attractive for tissue engineering. In our study, in addition to antibacterial effects of ZnO NPs, we show for the first time that ZnO NPs can foster the metabolic activity of fibroblasts as well as endothelial cells, both cell types being crucial for successful implant integration. With the gelatin sponge method performed on the chicken embryo's chorioallantoic membrane (CAM), we furthermore confirmed the high biocompatibility of ZnO NPs. In summary, we found ZnO NPs to have very favorable properties for the modification of biomaterials. Here, incorporation of ZnO NPs could help to guide the tissue reaction and promote complication-free healing.

Objectives: To compare clinical and radiological outcomes of narrow-diameter implants (NDI) placed in pristine bone to standard-diameter implants placed in combination with horizontal bone augmentation procedures (SDI+A) for horizontally deficient alveolar ridges., Material and Methods: For this retrospective study, the outcome of 597 NDI (∅ 3.3 mm, 272 patients), inserted in pristine bone, were compared with 180 SDI (∅ 4.1 mm, 83 patients), inserted in combination with horizontal augmentation procedures. Oral health-related quality of life was assessed in patients available for recall., Results: After a mean follow-up of 37.6 ± 40 months for the NDI and of 42.4 ± 49 months for the SDI+A, survival rates were 96.1% for NDI and 95.6% for SDI+A. Cumulative 5-year and 10-year implant survival rates were 94.3% and 92.2% for the NDI group and 97.0% and 88.3% for the SDI+A group, indicating no significant difference (p = .89). According to the criteria of Buser et al., an implant success rate of 84.3% was obtained for the NDI and an implant success rate of 81.3% for the SDI+A (p = .79). Regarding oral health-related quality of life, a similar and high patient satisfaction could be observed in both groups., Conclusions: NDI without augmentation procedures showed a similar clinical outcome as SDI in combination with augmentation procedures after a follow-up of more than 3 years. Therefore, NDI might be a reasonable alternative in cases of horizontal bone atrophy (no clinical trial registration as patient inclusion started 2003)., (© 2021 The Authors. Clinical Oral Implants Research published by John Wiley & Sons Ltd.)

Background: The primary aim of the study was to evaluate mini implant (MDI) survival, prosthodontic maintenance, and patient-reported outcome measures after conducting an optional pregraduate academic course on patients with mandibular edentulism including fabrication of overdentures and MDI planning and placement as well as chair-side incorporation of the respective restauration. In a prospective clinical study, 20 patients received 80 MDIs that were restored with mandibular overdentures. All treatment steps including placement of 40 MDIs were conducted by undergraduate students under strict guidance of a consultant. Next to students' perceptions after participation, survival of MDIs, and prosthodontic maintenance, patients' perceptions as well as peri-implant parameters were assessed after 4 weeks and 3 and 12 months., Results: Three MDIs fractured (two during insertion and one after 3 months; total survival 96.25%). Two overdentures fractured and a total of 23 cases of minor prosthodontic maintenance were required. Over time, patients' satisfaction significantly increased. Besides, questionnaires showed a high rate of students' positive perception and high self-confidence to include MDI therapy into own practice., Conclusions: The results are in accordance to those reported by postgraduate dentists. In accordance, therapy with MDI-retained mandibular overdentures seems to be feasible and successful at pregraduate level if the students receive guidance., (© 2021. The Author(s).)

Background: Hyperspectral imaging (HSI) is a promising non-contact approach to tissue diagnostics, generating large amounts of raw data for whose processing computer vision (i.e. deep learning) is particularly suitable. Aim of this proof of principle study was the classification of hyperspectral (HS)-reflectance values into the human-oral tissue types fat, muscle and mucosa using deep learning methods. Furthermore, the tissue-specific hyperspectral signatures collected will serve as a representative reference for the future assessment of oral pathological changes in the sense of a HS-library., Methods: A total of about 316 samples of healthy human-oral fat, muscle and oral mucosa was collected from 174 different patients and imaged using a HS-camera, covering the wavelength range from 500 nm to 1000 nm. HS-raw data were further labelled and processed for tissue classification using a light-weight 6-layer deep neural network (DNN)., Results: The reflectance values differed significantly (p < .001) for fat, muscle and oral mucosa at almost all wavelengths, with the signature of muscle differing the most. The deep neural network distinguished tissue types with an accuracy of > 80% each., Conclusion: Oral fat, muscle and mucosa can be classified sufficiently and automatically by their specific HS-signature using a deep learning approach. Early detection of premalignant-mucosal-lesions using hyperspectral imaging and deep learning is so far represented rarely in in medical and computer vision research domain but has a high potential and is part of subsequent studies., (© 2021. The Author(s).)

Bilateral sagittal split osteotomy (BSSO) of the mandible according to Obwegeser/Dal Pont is considered to be gold standard in orthognathic surgery. Frequently reported complications of BSSO are injuries of the mandibular nerve resulting in paresthesia/anesthesia as well as inadequate mandibular bone fracturing ('bad split'). High oblique sagittal osteotomy (HOSO) was introduced to overcome these complications. We present an innovative HOSO modification using patient-specific 3D-printed cutting guides positioned on the outside of the ascending mandibular ramus and fixed in the incisura semilunaris, precisely marking the optimal height and angle of the osteotomy. Advantages are a decreased operation time due to the simplicity of this less invasive procedure, a potentially reduced frequency of mandibular nerve damage and bad splits as well as a lower bleeding risk., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2021.)

This study aimed to investigate the dynamic skin perfusion via hyperspectral imaging (HSI) after application of Articaine-4% ± epinephrine as well as epinephrine only. After the subcutaneous injection of (A100) Articaine-4% with epinephrine 1:100,000, (A200) Articaine-4% with epinephrine 1:200,000, (Aw/o) Articaine-4% without epinephrine, and (EPI200) epinephrine 1:200,000, into the flexor side of the forearm in a split-arm design, dynamic skin perfusion measurement was performed over 120 min by determining tissue oxygen saturation (StO 2 ) using HSI. After injection, all groups experienced a reactive hyperaemia. With A200, it took about three min for StO 2 to drop below baseline. For Aw/o and EPI200, perfusion reduction when compared to baseline was seen at 30 min with vasoconstriction >120 min. A100 caused vasodilation with hyperaemia >60 min. After three minutes, the perfusion pattern differed significantly ( p < 0.001) between all groups except Aw/o and EPI200. The vasoactive effect of epinephrine-containing local anaesthetics can be visualised and dynamically quantified via StO2 using HSI. Aw/o + epinephrine 1:100,000 and 1:200,000 leads to perfusion reduction and tissue ischaemia after 30 min, which lasts over 120 min with no significant difference between both formulations. When using Aw/o containing epinephrine in terms of haemostasis for surgical procedures, a prolonged waiting time before incision of 30 or more min can be recommended.

Background and Purpose: The aim of this clinical study was to investigate the clinical long-term and patient-reported outcome of dental implants in patients with oral cancer. In addition, analysis of the influence of radiation therapy, timing of implant insertion, and augmentation procedures on implant survival was performed., Material and Methods: This retrospective study investigated the clinical outcome of 711 dental implants in 164 oral cancer patients, inserted by experienced surgeons of the Department of Oral and Maxillofacial Surgery, University Medical Center Mainz, Germany. Oral health-related quality of life (OHRQoL) was evaluated., Results: Cumulative 5-year and 10-year implant survival rates for all included implants were 87.3% and 80.0%. Implants placed straight after ablative surgery (primary implant placement) and implants placed after completing the oncologic treatment (secondary implant placement) showed a comparable implant survival (92.5% vs. 89.5%; p = 0.635). Irradiation therapy had no significant influence on implant survival of secondary placed implants (p = 0.929). However, regarding implant site (native bone vs. augmented bone) and radiation therapy (non-irradiated bone vs. irradiated bone), implants inserted in irradiated bone that received augmentation procedures showed a statistically significant lower implant survival (p < 0.001). Patients reported a distinct improvement in OHRQoL., Conclusions: Promising long-term survival rates of dental implants in patients after treatment of oral cancer were seen. In addition, patients benefit in form of an improved OHRQoL. However, bone augmentation procedures in irradiated bone may result in an impaired implants' prognosis., (© 2021. The Author(s).)

(1) Background: This cross-sectional study aims to compare a new and non-invasive approach using hyperspectral imaging (HSI) with the conventional modified Allen's test (MAT) for the assessment of collateral perfusion prior to radial forearm free flap harvest in healthy adults. (2) HSI of the right hand of 114 patients was recorded. Here, three recordings were carried out: (I) basic status (perfusion), (II) after occlusion of ulnar and radial artery (occlusion) and (III) after releasing the ulnar artery (reperfusion). At all recordings, tissue oxygenation/superficial perfusion (StO 2 (0-100%); 0-1 mm depth), tissue hemoglobin index (THI (0-100)) and near infrared perfusion index/deep perfusion (NIR (0-100); 0-4 mm depth) were assessed. A modified Allen's test (control) was conducted and compared with the HSI-results. (3) Results: Statistically significant differences between perfusion (I) and artery occlusion (II) and between artery occlusion (II) and reperfusion (III) could be observed within the population with a non-pathological MAT (each <0.001). Significant correlations were observed for the difference between perfusion and reperfusion in THI and the height of the MAT ( p < 0.05). Within the population with a MAT >8 s, an impairment in reperfusion was shown (each p < 0.05) and the difference between perfusion and reperfusion exhibited a strong correlation to the height of the MAT (each p < 0.01). (4) Conclusions: The results indicate a reliable differentiation between perfusion and occlusion by HSI. Therefore, HSI could be a useful tool for verification of the correct performance of the MAT as well as to confirm the final diagnosis, as it provides an objective, reproducible method whose results strongly correlate with those obtained by MAT. What is more, it can be easily applied by non-medical personnel.

(1) Background: In response to the global COVID-19 pandemic, governmental measures have been undertaken. The impact of the crisis on the healthcare of patients with cancer is largely unexplored. This multicenter cohort study aimed to investigate a potential screening delay and its consequences in patients with oral cancer (OC) during the pandemic. (2) Material and Methods: Data of patients who were first diagnosed with OC during different periods were collected, especially in terms of OC incidence, tumor stage/entity and time to intervention. The periods lockdown (LD) (13 March-16 June 2020), post-lockdown (PLD) (17 June-1 November 2020), and the corresponding equivalents in 2018/19 were differentiated and compared. (3) Results: There was no obvious trend towards a higher incidence of OC or higher tumor stages, whereas a trend towards a shorter time to intervention during the LD2020 could be observed. Subgroup analyses revealed an increased incidence in OC within the PLD2020 in Mainz, which might be explained by the partial closure of dental practices in this federal state during LD. (4) Conclusions: While there was no overall higher incidence of OC, we found closure of practices during LD to possibly delay cancer diagnosis. Therefore, measures must be taken to identify patients at risk and to ensure basic healthcare, especially in the context of dental screening measures.

Bovine bone substitute materials (BSMs) are used for oral bone regeneration. The objective was to analyze the influence of BSM biofunctionalization via hyaluronic acid (HA) on human osteoblasts (HOBs). BSMs with ± HA were incubated with HOBs including HOBs alone as a negative control. On days 3, 7 and 10, cell viability, migration and proliferation were analyzed by fluorescence staining, scratch wound assay and MTT assay. On days 3, 7 and 10, an increased cell viability was demonstrated for BSM+ compared with BSM- and the control (each p ≤ 0.05). The cell migration was enhanced for BSM+ compared with BSM- and the control after day 3 and day 7 (each p ≤ 0.05). At day 10, an accelerated wound closure was found for the control compared with BSM+/- (each p < 0.05). The highest proliferation rate was observed for BSM+ on day 3 ( p ≤ 0.05) followed by BSM- and the control (each p ≤ 0.05). At day 7, a non-significantly increased proliferation was shown for BSM+ while the control was higher than BSM- (each p < 0.05). The least proliferation activity was observed for BSM- ( p < 0.05) at day 10. HA biofunctionalization of the BSMs caused an increased HOB activity and might represent a promising alternative to BSM- in oral bone regeneration.

Objectives: The aim of this clinical analysis was to evaluate intraoperative and early postoperative complications as well as late findings and the overall patient satisfaction following orthognathic surgery., Materials and Methods: In a retrospective, cross-sectional study, 119 patients after orthognathic surgery were included. Surgical approaches were single bilateral sagittal split osteotomy (BSSO (n = 52)), single LeFort-I osteotomy (n = 5) and bimaxillary osteotomy (LeFort-I + BSSO (n = 62)). Intraoperative and early (0-4 weeks postoperative) complications were investigated retrospectively (n = 119), whereas late findings and quality of life were assessed via clinical follow-up and survey (mean: 59 months postoperative) on 48 patients., Results: Bad split (n = 4/114) was the most common intraoperative complication followed by one case of severe bleeding. Regarding early postoperative complications, temporary damage of the inferior alveolar nerve after BSSO was most common (n = 33/114), followed by facial nerve dysfunction (n = 3), failed osteosynthesis (n = 2) and one case of postoperative dyspnoea. Permanent hypaesthesia of the lower lip was the most prevalent (n = 28/45 (BSSO and LeFort-I + BSSO) ) late finding with varying extent, followed by temporomandibular dysfunction (TMD) (n = 25/48). Skeletal relapse mostly occurred after class II treatment, followed by class III, posterior crossbite and open bite. Overall, the surgery improved the patients' self-perception (85.4%), with 60.4% of patients opting for surgery again., Conclusions: Long-term complications after orthognathic surgery occurred more frequently than commonly described in the literature, and analyses of the quality of life show the need for more comprehensive preoperative patient education., Clinical Relevance: Hypaesthesia of the lower lip presented less as complication but rather as side effect following BSSO. As orthognathic surgery is mostly elective, preoperative patient education is of pivotal importance and should include proactive risk stratification.

(1) Background: Primary stability-one fundamental criterion for the success of dental implants-is influenced by implant geometry even if the effect of apical shape modifications on implant primary stability has not yet been examined. Therefore, the aim of the ex vivo study was to compare primary stability of implants differing in apically located screw threads (J-line) or a flat tip (K-line) only. (2) Methods: 28 implants of each group of the same diameter (4.3 mm) were randomly inserted into porcine bone blocks. The first group (9, 11 and 13 mm) was inserted into "hard", the second (11 mm) into "soft" bone, here using a normal and an undersized drilling protocol. Insertion torque (Ncm), Periotest ® value, resonance frequency (implant stability coefficient, ISQ) and push-out force (N) were measured. (3) Results: In "hard" bone, primary stability increased with increasing length in both groups but it was significantly higher in J-line ( p < 0.03). An undersized preparation of the implant bed in "soft" bone resulted in a significant increase in primary stability in both groups. Here, J-line also showed a significantly increased primary stability when compared to equally prepared K-line (insertion torque: 37 Ncm vs. 26 Ncm; Periotest ® : -6.5 vs. -4.3; push-out force: 365 N vs. 329 N; p < 0.05 each). (4) Conclusions: Primary stability is significantly higher with increasing implant length and apically located screw threads as well as with undersized drilling protocols. When preparing the implant site and subsequently selecting the implant system, modifying factors such as implant geometry (also at the tip) should be taken into account.

Bone substitute materials (BSM) are widely used in oral regeneration, but sufficient angiogenesis is crucial for osteogenesis. The combination of BSM with autologous thrombocyte concentrations such as platelet-rich fibrin (PRF) may represent a clinical approach to overcome this limitation. This study analyzes the early influence on osteoblast (HOB) in vitro . Here, four different BSM (allogeneic, alloplastic, and two of xenogeneic origin) were combined with PRF. After the incubation with osteoblasts for 24 h, cell viability, migration, and proliferation were assessed. Next, marker of proliferation, migration, and differentiation were evaluated on gene and protein levels in comparison to the native BSM and osteoblast alone. Addition of PRF increased viability for both the xenogeneic BSM ( p = 0.0008, p = 0.032, respectively) in comparison to HOB and vs. native BSM ( p = 0.008), and led to a tendency for increased cell proliferation and migration for all BSM (each p > 0.05). On gene basis, allogeneic and alloplastic BSM displayed a significantly increased RUNX2 expression (each p = 0.050). Expression of alkaline phosphatase for alloplastic ( p = 0.050) and collagen-1 for xenogeneic BSM ( p = 0.05) were significantly increased in combination with PRF. In addition, bone morphogenic protein was expressed significantly higher when xenogeneic material was combined with PRF in comparison to HOB alone (each p = 0.05). In summary, the combination of PRF with different BSM increases initial viability and may influence early proliferation and migration potential of osteoblast via RUNX2, alkaline phosphatase, collagen, and BMP2 especially in combination with alloplastic and xenogeneic BSM. Biofunctionalization of BSM using PRF might improve osteogenesis and extend the range of indications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Blatt, Thiem, Kyyak, Pabst, Al-Nawas and Kämmerer.)

Objectives: In reconstructive surgery, flap monitoring is crucial for early identification of perfusion problems. Using hyperspectral imaging (HSI), this clinical study aimed to develop a non-invasive, objective approach for perfusion monitoring of free and pedicled flaps., Material and Methods: HSI of 22 free (FF) and 8 pedicled flaps (PF) in 30 patients was recorded over time. Parameters assessed were tissue oxygenation/superficial perfusion (0-1 mm) (StO 2 (0-100%)), near-infrared perfusion/deep perfusion (0-4 mm) (NIR (0-100)), distribution of haemoglobin (THI (0-100)), and water (TWI (0-100)). Measurements up to 72 h were correlated to clinical assessment., Results: Directly after flap inset, mean StO 2 was significantly higher in FF (70.3 ± 13.6%) compared with PF 56.2 ± 14.2% (p = 0.05), whereas NIR, THI, and TWI were similar (NIR&#95;p = 0.82, THI&#95;p = 0.97, TWI&#95;p = 0.27). After 24 h, StO 2 , NIR, THI, and TWI did not differ between FF and PF. After 48 h, StO 2 , NIR, and TWI did not differ between FF and PF whereas THI was significantly increased in FF compared with PF(p = 0.001). In three FF, perfusion decreased clinically and in HSI, 36 (1) , 40 (2) , 5 (3 ), and 61 (3) h after flap inset which was followed by prompt intervention., Conclusions: StO 2 < 40%, NIR < 25/100, and THI < 40/100 indicated arterial occlusion, whereas venous problems revealed an increase of THI. In comparison with FF, perfusion parameters of PF were decreased after flap transfer but remained similar to FF later on., Clinical Relevance: HSI provides objective and non-invasive perfusion monitoring after flap transplantation in accordance to the clinical situation. With HSI, signs of deterioration can be detected hours before clinical diagnosis.

Introduction: The aim of the in vitro study was to compare the effect of four bovine bone substitute materials (XBSM) with and without injectable platelet-reach fibrin for viability and metabolic activity of human osteoblasts (HOB) as well as expression of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2), and osteonectin (OCN)., Materials and Methods: Cerabone ® (CB), Bio-Oss ® (BO), Creos Xenogain ® (CX) and MinerOss ® X (MO) ± i-PRF were incubated with HOB. At day 3, 7, and 10, cell viability and metabolic activity as well as expression of ALP, OCN, and BMP-2, was examined., Results: For non-i-PRF groups, the highest values concerning viability were seen for CB at all time points. Pre-treatment with i-PRF increased viability in all groups with the highest values for CB-i-PRF after 3 and 7 and for CX-i-PRF after 10 days. For metabolic activity, the highest rate among non-i-PRF groups was seen for MO at day 3 and for CB at day 7 and 10. Here, i-PRF groups showed higher values than non-i-PRF groups (highest values: CB + i-PRF) at all time points. There was no difference in ALP-expression between groups. For OCN expression in non-i-PRF groups, CB showed the highest values after day 3, CX after day 7 and 10. Among i-PRF-groups, the highest values were seen for CX + i-PRF. At day 3, the highest BMP-2 expression was observed for CX. Here, for i-PRF groups, the highest increase was seen for CX + i-PRF at day 3. At day 7 and 10, there was no significant difference among groups., Conclusion: XBSM sintered under high temperature showed increased HOB viability and metabolic activity through the whole period when compared to XBSM manufactured at lower temperatures. Overall, the combination of XBSM with i-PRF improved all cellular parameters, ALP and BMP-2 expression at earlier stages as well as OCN expression at later stages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kyyak, Blatt, Schiegnitz, Heimes, Staedt, Thiem, Sagheb, Al-Nawas and Kämmerer.)

Background: Immunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates. The study aimed to investigate the influence of bisphosphonates alone and in combination with surgical trauma on systemic macrophage polarization (M1 vs. M2) using an in vivo rat model., Methods: A total of 120 animals were divided into four groups. Groups 2 and 4 were treated with 8 × 40 μg/kg body weight of the BP Zoledronate i.p. (week 0-7). Groups 3 and 4 were exposed to surgical trauma (week 8, tooth extraction + tibia fracture), whereas in Group 1 neither medication nor surgical trauma was applied. After 8, 10, 12 and 16 weeks, skin, lung and spleen were immunohistochemically examined for macrophage polarization via expression analysis of CD68, CD163 and iNOS using a tissue microarray (TMA)., Results: A significant shift of macrophage polarization towards M1 was observed in skin, spleen and lung tissue of animals, with and without surgical trauma, treated with BP when compared to those without BP application. Surgical trauma did not cause a significant increase towards M1 polarization., Conclusions: BP application leads to a systemic pro-inflammatory situation in vivo, independent of surgical trauma, as evidenced by the shift in macrophage polarization towards M1 in various somatic tissues. This provides a possible explanation for the clinically observed anti-tumor effect of bisphosphonates and might also contribute to pathogenesis of MRONJ., Competing Interests: The authors declare that they have no competing interests.

The impaired angiogenic potential of bone substitute materials (BSMs) may limit regenerative processes. Therefore, changes in the angiogenetic properties of different BSMs in combination with platelet-rich fibrin (PRF) in comparison to PRF alone, as well as to native BSMs, were analyzed in vitro and in vivo to evaluate possible clinical application. In vitro, four BSMs of different origins (allogeneic, alloplastic, and xenogeneic) were biofunctionalized with PRF and compared to PRF in terms of platelet interaction and growth factor release (vascular endothelial growth factor (VEGF), tissue growth factor ß (TGFß) and platelet-derived growth factor (PDGF)) after 15 min. To visualize initial cell-cell interactions, SEM was performed. In vivo, all BSMs (±PRF) were analyzed after 24 h for new-formed vessels using a chorioallantoic membrane (CAM) assay. Especially for alloplastic BSMs, the addition of PRF led to a significant consumption of platelets ( p = 0.05). PDGF expression significantly decreased in comparison to PRF alone (all BSMs: p < 0.013). SEM showed the close spatial relation of each BSM and PRF. In vivo, PRF had a significant positive pro-angiogenic influence in combination with alloplastic ( p = 0.007) and xenogeneic materials ( p = 0.015) in comparison to the native BSMs. For bio-activated xenogeneic BSMs, the branching points were also significantly increased ( p = 0.005). Finally, vessel formation was increased for BSMs and PRF in comparison to the native control (allogeneic: p = 0.046; alloplastic: p = 0.046; and xenogeneic: p = 0.050). An early enhancement of angiogenetic properties was demonstrated when combining BSMs with PRF in vitro and led to upregulated vessel formation in vivo. Thus, the use of BSMs in combination with PRF may trigger bony regeneration in clinical approaches.

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α 1 - and β 1 -subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α 1 - and β 1 -subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α 1 - and β 1 -subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.

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.

Background: The aim was to compare early biochemical and histological osseous healing of chronic mandibular defects regenerated with bovine bone substitute with and without collagen membrane in vivo., Methods: Eight weeks after formation of a lateral full-thickness perforating bone defect in the mandible of 40 rabbits, bovine bone substitute with ("+";n = 20) and without ("-";n = 20) collagen membrane was applied. Blood and bone was collected 24, 72 h, 7, 14 and 21 days after surgery. Total acid phosphatase, bone acid phosphatase, total alkaline phosphatase and bone alkaline phosphatase activities were compared between groups. Formation of new bone was quantified histologically for all time points., Results: Twenty-four hours after surgery, bone alkaline phosphatase was significantly elevated in "+" group when compared to "-" (p=0.012). After 72 hours, all bone turnover markers except for total acid phosphatase (p=0.078) where significantly elevated in "+" (all p < 0.05). Fourteen days after surgery, the significant highest values for all bone turnover markers were detected in "-" (all p < 0.05). A significant difference in favor of group "-" could also be detected after 3 weeks in terms of both acid phosphatases (p < 0.05). In histology, no significant differences could be detected., Conclusion: Bone regeneration with bovine bone substitute material and collagen membrane shows a significantly earlier bone remodeling activity but does not seem to influence formation of new bone in histological samples.

Human gingival fibroblasts (HGF) play a vital role in wound healing, oral cancer, and are among the first cells being exposed to e-cigarette vapor (eCV) or cigarette smoke (CS) during inhalation. Although the cell-damaging effect of CS has been well studied, the effects of eCV on gingival cells are still unclear. The aim of this in vitro study was to compare the effects of eCV and CS on HGF in terms of proliferation, metabolic activity, cell death, and formation of reactive oxygen species (ROS). After 24 h cell numbers in CS-exposed cells in contrast to eCV-exposed cells were significantly decreased compared to the control. At later points in time, such differences could no longer be observed. Compared to the control, HGF stimulated with eCV showed a significantly higher metabolic activity 1 h, 24 h, and 48 h after exposure. 24 h after exposure, the metabolic activity was increased in both test groups. No caspase 3/7 activation nor significant differences in the amount of apoptosis/necrosis among the groups were seen. Only in CS-exposed cells ROS formation was increased at 1 h, 3 h, and 6 h after exposition. In conclusion, when compared to conventional CS, a less harmful effect of eCV on HGF can be assumed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim of the study was to compare the evolvement of vascularization over time of collagen membranes (CMs) of dermal and pericardial origin in an in vivo animal study. Twenty-eight mice underwent implantation of three commercially available CM derived from porcine dermis (homogenous structure: CM1 (Control 1) and bilayer structure: CM2 [Control 2]), from porcine pericardium (CM3; Test 1) as well as CM3 sprayed with silica-enhanced nanostructured hydroxyapatite (CM4, Test 2). After 3, 6, 9, and 12 days, intravital fluorescence microscopy was conducted for determination of capillary diameter, density, flow, and length. At Day 12, samples were examined immunohistologically for expression of fibroblast growth factor receptor 4 (FGFR4), CD11b, CD68, αSMA, and CD34. In all CM, intravital fluorescence microscopy over time showed increasing values for all parameters with the highest levels in CM4 and the lowest values in CM1. Significant lower amounts of FGFR4, CD11b, and CD68 were detected in CM4 when compared to CM2 (p < .05). In contrast to CM3, lower values of αSMA and higher numbers of CD34 positive-marked vessels were observed in CM4 (p < .05). In conclusion, dermal bilayer as well as pericardial CM seem to have a higher vascularization rate than dermal homogenous CM. Additional coating of pericardial CM with a silica-enhanced hydroxyapatite increases the speed of vascularization as well as biological remodeling processes., (© 2020 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals, Inc.)

Study Design: The aim of this study was to evaluate the accuracy of 3-dimensional (3D)-planned maxillary positioning by using computer-assisted design (CAD)/computer-assisted manufacturing (CAM) splints combined with temporary mandibular fixation in bimaxillary orthognathic surgery. In orthognathic surgery, customized splints work sufficiently well to transfer preoperative planning into the operation site for transverse und sagittal positioning of the maxilla. The vertical positioning is more difficult due to the non-fixed mandibular reference. Therefore, the combined use of CAD/CAM splints and temporary mandibular fixation to the zygomatic region was applied for transferring the 3D-planned maxillary position into the operation site from 2012 until 2015 in our hospital., Objective: In addition to the general accuracy, the precision should therefore be checked especially in the vertical plane compared to axial and sagittal plane., Methods: In this retrospective study, we calculated the deviation of 5 occlusal landmarks of the maxilla in 35 consecutive patients by fusing preoperative 3D planning images and postoperative computed tomography scans after bimaxillary surgery., Results: The overall median deviation of maxillary positioning between plan and surgical result was 0.99 mm. The accuracy of left-right positioning was median 0.96 mm. Anterior-posterior positioning of the maxilla showed a median accuracy of 0.94 mm. Just slightly higher values were determined for the upward-downward positioning (median 1.06 mm)., Conclusions: This demonstrates the predictability of maxillary positioning by using CAD/CAM splints in combination with temporary mandibular fixation in all 3 axes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: The aim of this study was to analyze potential risk factors for early and late dental implant failure (DIF) in a clinical cohort trial. In a private practice, 9080 implants were inserted during a period of 10 years. In case of DIF, data were classified into early and late DIF and compared to each other in regard of gender, age, site of implantation, implant geometry, and patients' systemic diseases., Results: Three hundred fifty-one implants failed within the observation period (survival rate: 96.13%). Early DIF occurred in 293 implants (83.48%) compared to late DIF in 58 implants (16.52%). Significant earlier DIF was seen in the mandible (OR = 3.729, p < 0.001)-especially in the posterior area-and in younger patients (p = 0.017), whereas an increased likelihood of late DIF was associated with maxillary implants (OR = 3.729, p < 0.001) and older patients., Conclusions: Early DIF is about twice as common as late DIF. Main risk factors for early DIF are implant location in the (posterior) mandible as well as younger age. On contrary, late DIF is rather associated with older patients, cancellous bone quality, and longer implants.