Publications by authors named "Bilal Al-Nawas"

178 Publications

Hyperspectral imaging and artificial intelligence to detect oral malignancy - part 1 - automated tissue classification of oral muscle, fat and mucosa using a light-weight 6-layer deep neural network.

Head Face Med 2021 Sep 3;17(1):38. Epub 2021 Sep 3.

Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, University Medical Centre Mainz, Augustusplatz 2, 55131, Mainz, Germany.

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.
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http://dx.doi.org/10.1186/s13005-021-00292-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414848PMC
September 2021

Hyperspectral Imaging to Study Dynamic Skin Perfusion after Injection of Articaine-4% with and without Epinephrine-Clinical Implications on Local Vasoconstriction.

J Clin Med 2021 Jul 31;10(15). Epub 2021 Jul 31.

Department of Oral and Maxillofacial Surgery, University Medical Centre Mainz, 55131 Mainz, Germany.

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) using HSI. After injection, all groups experienced a reactive hyperaemia. With A200, it took about three min for StO 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 ( < 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.
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http://dx.doi.org/10.3390/jcm10153411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347280PMC
July 2021

Response to the letters to the editor: Neuralgia-inducing cavitational osteonecrosis-A systematic review.

Oral Dis 2021 Jul 21. Epub 2021 Jul 21.

Department of Oral and Maxillofacial Surgery, University Hospital Heidelberg, Heidelberg, Germany.

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http://dx.doi.org/10.1111/odi.13971DOI Listing
July 2021

Clinical long-term and patient-reported outcomes of dental implants in oral cancer patients.

Int J Implant Dent 2021 Jul 13;7(1):93. Epub 2021 Jul 13.

Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre, Johannes Gutenberg-University, Mainz, Germany.

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.
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http://dx.doi.org/10.1186/s40729-021-00373-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276905PMC
July 2021

Treatment concepts of horizontally deficient ridges-A retrospective study comparing narrow-diameter implants in pristine bone with standard-diameter implants in augmented bone.

Clin Oral Implants Res 2021 Jul 5. Epub 2021 Jul 5.

Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany.

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).
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http://dx.doi.org/10.1111/clr.13807DOI Listing
July 2021

Antimicrobial Resistance and the Spectrum of Pathogens in Dental and Oral-Maxillofacial Infections in Hospitals and Dental Practices in Germany.

Front Microbiol 2021 2;12:676108. Epub 2021 Jun 2.

Robert Koch Institute, Unit 37: Nosocomial Infections, Surveillance of Antimicrobial Resistance and Consumption, Berlin, Germany.

Data on microbiological profiles in odontogenic infections are scarce. This study aimed to analyze the spectrum of pathogens and antimicrobial resistance in clinical isolates from dental and oral-maxillofacial clinical settings in Germany. We analyzed 20,645 clinical isolates (dental practices: = 5,733; hospitals: = 14,912) from patients with odontogenic infections using data (2012-2019) from the German (ARS) system. A total of 224 different species from 73 genera were found in clinical isolates from dental practices, and 329 different species from 97 genera were identified in isolates from hospital patients. In both hospitals and dental practices spp. (33 and 36%, respectively) and spp. (21 and 12%, respectively) were the most frequently isolated microorganisms. In spp. isolates from hospitals, penicillin and aminopenicillin resistance proportions were 8.0% (95%CI 4.7-14.9%) and 6.9% (95%CI 4.7-9.9%), respectively. Substantially lower resistance proportions of penicillin and aminopenicillin were observed in dental practices [2.6% (95%CI 1.4-4.7%) and 2.1% (95%CI 1.1-4.0%), respectively]. Among isolates from hospital patients methicillin resistance proportions were 12.0% (95%CI 9.7-14.8%), which was higher than in isolates from dental practices (5.8% (95%CI 4.1-8.1%)]. High clindamycin and macrolide resistance proportions (>17%) were observed in spp. and isolates. In spp. isolates carbapenem resistance proportions were <1%. In sum, substantial antibiotic resistance was observed in isolates from odontogenic infections, which calls for strengthened efforts in antibiotic stewardship and infection prevention and control measures in both hospitals and dental practices.
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http://dx.doi.org/10.3389/fmicb.2021.676108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206268PMC
June 2021

The role of diabetes mellitus on the formation of severe odontogenic abscesses-a retrospective study.

Clin Oral Investig 2021 May 13. Epub 2021 May 13.

Department of Oral and Maxillofacial Surgery - Facial plastic Surgery, Medical Center of the Johannes Gutenberg-University of Mainz, Augustusplatz 2, 55131, Mainz, Germany.

Objectives: To analyze the correlation of diabetes mellitus and hyperglycemia with severe odontogenic abscesses.

Materials And Methods: Records of all patients in the Department of Oral and Maxillofacial Surgery of the Medical Center of the Johannes Gutenberg-University who underwent inpatient treatment for severe odontogenic abscesses between 2010 and 2016 were evaluated retrospectively regarding diabetes anamnesis, maximum and fasting blood sugar count, and duration until discharge. In order to compare the numbers to a general maxillofacial group, all patients who received inpatient treatment in 2013 for any diagnosis other than an abscess of the head and neck region were analyzed as well, and the numbers were correlated.

Results: In total, 977 abscess patients were found in the analyzed period. 7.0% of the patients had a known diagnosis of diabetes mellitus type II and 0.6% of type I. Correlation with the general group showed that abscesses were significantly more likely in diabetics as well as patients with abnormal maximum and fasting blood sugar counts. These patients also needed significantly longer inpatient treatment.

Conclusions: Diabetics and patients with abnormal glucose tolerance show significantly higher numbers of severe odontogenic abscesses and might therefore benefit from earlier escalation of antibiotic medication.

Clinical Relevance: Severe odontogenic abscesses are one of the most frequent diagnoses in maxillofacial practice. Adjusting the therapeutic approach for diabetics or patients with abnormal blood sugar counts might help to prevent the development of abscesses.
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http://dx.doi.org/10.1007/s00784-021-03926-4DOI Listing
May 2021

Does the Modification of the Apical Geometry of a Dental Implant Affect Its Primary Stability? A Comparative Ex Vivo Study.

Materials (Basel) 2021 Apr 1;14(7). Epub 2021 Apr 1.

Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Augustusplatz 2, 55131 Mainz, Germany.

(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 ( < 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; < 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.
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http://dx.doi.org/10.3390/ma14071728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036940PMC
April 2021

Neuralgia-inducing cavitational osteonecrosis - A systematic review.

Oral Dis 2021 Apr 24. Epub 2021 Apr 24.

Department of Oral and Maxillofacial Surgery, University Hospital Heidelberg, Heidelberg, Germany.

Objective: To assess the aetiologic factors, proposed diagnostic means and treatment strategies for neuralgia-inducing cavitational osteonecrosis.

Methods: A search of the literature published up to June 2020 was conducted using Medline, the Cochrane Library, PsycINFO, CINAHL and Web of Science. The scientific quality of the evidence was rated according to NIH Quality Assessment Tools.

Results: 4,051 articles were found, 59 were reviewed in full text, and 29 studies were included. With the exception of hereditary coagulopathies, which were identified as potential risk factors in five studies, suggestions concerning the aetiology varied widely. No gold standard diagnostic mean could be identified. Treatment was most often performed by surgical curettage of the affected bone. Surgical treatment outcomes were equally varied: significant facial pain remission was reported in 66%-100% for periods varying between 2 months to 18 years, whereas no or little relief and recurrences were reported in up to ⅓ of cases. All studies were observational in their design. All investigations were rated as poor quality because of high risk of bias and non-transparent reporting.

Conclusions: Evidence concerning the aetiology, diagnosis and treatment of NICO is poor. Prospective diagnostic and therapeutic studies are needed before the usefulness of invasive therapeutic procedures can be evaluated.
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http://dx.doi.org/10.1111/odi.13886DOI Listing
April 2021

Possible Implications for Improved Osteogenesis? The Combination of Platelet-Rich Fibrin With Different Bone Substitute Materials.

Front Bioeng Biotechnol 2021 16;9:640053. Epub 2021 Mar 16.

Department of Oral and Maxillofacial Surgery, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

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) . 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 ( = 0.0008, = 0.032, respectively) in comparison to HOB and vs. native BSM ( = 0.008), and led to a tendency for increased cell proliferation and migration for all BSM (each > 0.05). On gene basis, allogeneic and alloplastic BSM displayed a significantly increased RUNX2 expression (each = 0.050). Expression of alkaline phosphatase for alloplastic ( = 0.050) and collagen-1 for xenogeneic BSM ( = 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 = 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.
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http://dx.doi.org/10.3389/fbioe.2021.640053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010662PMC
March 2021

Effect and timing of parathyroid hormone analog administration for preventing medication-related osteonecrosis of the jaws in a murine model.

J Craniomaxillofac Surg 2021 Aug 26;49(8):719-725. Epub 2021 Feb 26.

Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea; Department of Dentistry, Graduate School, Kyung Hee University, Seoul, Republic of Korea. Electronic address:

The aim of this study was to investigate the effect and timing of recombinant human parathyroid hormone analog (PTH) administration for preventing medication-related osteonecrosis of the jaws (MRONJ) using a murine model. After standardized MRONJ induction using zoledronic acid and dexamethasone injections, 48 female Sprague-Dawley rats were divided into four groups according to the timing of PTH administration before or after dental extraction. Rats were euthanized 3 weeks after dental extraction, followed by clinical and histologic analyses. No clinical improvements were observed in the preoperative and postoperative PTH groups, compared to controls (p = 0.638 and 0.496, respectively). However, on histological analysis, the number of empty lacunae reduced significantly, and the number of blood vessels increased in the preoperative PTH group (p = 0.004 and 0.002, respectively). The postoperative PTH group did not show significant differences for empty lacunae and blood vessels compared to controls (p = 0.075 and 0.194, respectively). The reduction in the empty lacunae and the increase in the blood vessels in the preoperative PTH group were significant compared to other groups, suggesting more viable bone tissue in this group. In perspective, preoperative PTH use may represent a better prophylactic regimen for preventing the occurrence of MRONJ after traumatic dental or surgical procedures, especially in patients with a history of long-term bisphosphonate administration or at high risk of developing MRONJ. However, the findings should be proven in further studies on other animals followed by clinical trials.
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http://dx.doi.org/10.1016/j.jcms.2021.02.023DOI Listing
August 2021

Activation of Human Osteoblasts via Different Bovine Bone Substitute Materials With and Without Injectable Platelet Rich Fibrin .

Front Bioeng Biotechnol 2021 17;9:599224. Epub 2021 Feb 17.

Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Mainz, Germany.

Introduction: The aim of the 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.
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http://dx.doi.org/10.3389/fbioe.2021.599224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925396PMC
February 2021

Patient-specific titanium meshes: Future trend or current technology?

Clin Implant Dent Relat Res 2021 02;23(1):3-4

Private Practice for Oral and Maxillofacial Surgery, Private Practice Dr. Seiler and Colleagues, Filderstadt, Germany.

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http://dx.doi.org/10.1111/cid.12981DOI Listing
February 2021

Factors accelerating recurrences and secondary tumors in cutaneous squamous cell carcinoma.

J Craniomaxillofac Surg 2021 Apr 12;49(4):317-322. Epub 2021 Feb 12.

Department of Oral and Maxillofacial Surgery of the University Medical Center of the Johannes Gutenberg-University, Augustusplatz 2, 55131, Mainz, Germany.

To investigate factors that affect and also decrease the duration for recurrences and secondary tumors in cSCC. A retrospective study was conducted for all patients who were treated for a cSCC of the head and neck between 2009 and 2016. Anamnestic as well as epidemiological and histological data were noted and correlated with the occurrence of recurrences and secondary cancers. The duration between surgery and these events was used to determine if histological factors accelerate their occurrence. The highest risk for recurrences was seen in patients with previous skin cancers (RR 3.23). Histological ulceration (p = 0.003) and grading (p = 0.031) of the tumor were found as significant factors accelerating the time to relapse. Surrounding chronic precancerotic lesions (p < 0.001) and poor tumor grading (p = 0.035) were found as significant factors accelerating the time until a secondary cSCC was observed. Known risk factors increase not only the risk for a cSCC but also for recurrences. Specific histologic findings can help to adjust follow-up intervals to identify recurrences and secondary tumors at an early stage as these were shown to decrease the duration for a further event.
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http://dx.doi.org/10.1016/j.jcms.2021.02.009DOI Listing
April 2021

Calcium Phosphate-Coated Titanium Implants in the Mandible: Limitations of the in vivo Minipig Model.

Eur Surg Res 2020 18;61(6):177-187. Epub 2021 Feb 18.

Department of Oral, Maxillofacial and Plastic Surgery, University Medical Center Mainz, Mainz, Germany.

Introduction: We aimed to compare implant osseointegration with calcium phosphate (CaP) surfaces and rough subtractive-treated sandblasted/acid etched surfaces (SA) in an in vivo minipig mandible model.

Materials And Methods: A total of 36 cylindrical press-fit implants with two different surfaces (CaP, n = 18; SA, n = 18) were inserted bilaterally into the mandible of 9 adult female minipigs. After 2, 4, and 8 weeks, we analyzed the cortical bone-to-implant contact (cBIC; %) and area coverage of bone-to-implant contact within representative bone chambers (aBIC; %).

Results: After 2 weeks, CaP implants showed no significant increase in cBIC and aBIC compared to SA (cBIC: mean 38 ± 5 vs. 16 ± 11%; aBIC: mean 21 ± 1 vs. 6 ± 9%). Two CaP implants failed to achieve osseointegration. After 4 weeks, no statistical difference between CaP and SA was seen for cBIC (mean 54 ± 15 vs. 43 ± 16%) and aBIC (mean 43 ± 28 vs. 32 ± 6). However, we excluded two implants in each group due to failure of osseointegration. After 8 weeks, we observed no significant intergroup differences (cBIC: 18 ± 9 vs. 18 ± 20%; aBIC: 13 ± 8 vs. 16 ± 9%). Again, three CaP implants and two SA implants had to be excluded due to failure of osseointegration.

Conclusion: Due to multiple implant losses, we cannot recommend the oral mandibular minipig in vivo model for future endosseous implant research. Considering the higher rate of osseointegration failure, CaP coatings may provide an alternative to common subtractive implant surface modifications in the early phase post-insertion.
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http://dx.doi.org/10.1159/000513846DOI Listing
February 2021

Does Platelet-Rich Fibrin Enhance the Early Angiogenetic Potential of Different Bone Substitute Materials? An In Vitro and In Vivo Analysis.

Biomedicines 2021 Jan 10;9(1). Epub 2021 Jan 10.

Department of Oral and Maxillofacial Surgery, University Medical Center, Augustusplatz 2, 55131 Mainz, Germany.

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 ( = 0.05). PDGF expression significantly decreased in comparison to PRF alone (all BSMs: < 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 ( = 0.007) and xenogeneic materials ( = 0.015) in comparison to the native BSMs. For bio-activated xenogeneic BSMs, the branching points were also significantly increased ( = 0.005). Finally, vessel formation was increased for BSMs and PRF in comparison to the native control (allogeneic: = 0.046; alloplastic: = 0.046; and xenogeneic: = 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.
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http://dx.doi.org/10.3390/biomedicines9010061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827266PMC
January 2021

A collagen membrane influences bone turnover marker in vivo after bone augmentation with xenogenic bone.

Head Face Med 2020 Dec 7;16(1):35. Epub 2020 Dec 7.

Department of Oral, Maxillofacial Plastic Surgery, University Medical Center Mainz, Augustusplatz 2, 55131, Mainz, Germany.

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.
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http://dx.doi.org/10.1186/s13005-020-00249-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722310PMC
December 2020

Potential risk factors for early and late dental implant failure: a retrospective clinical study on 9080 implants.

Int J Implant Dent 2020 Nov 30;6(1):81. Epub 2020 Nov 30.

Department of Oral and Maxillofacial Surgery, University Medical Center Mainz, Augustusplatz 2, 55131, Mainz, Germany.

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.
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http://dx.doi.org/10.1186/s40729-020-00276-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701040PMC
November 2020

Continuous Electrical Stimulation Affects Initial Growth and Proliferation of Adipose-Derived Stem Cells.

Biomedicines 2020 Nov 8;8(11). Epub 2020 Nov 8.

Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, University Medical Center Rostock, 18057 Rostock, Germany.

The aim of the study was to establish electrical stimulation parameters in order to improve cell growth and viability of human adipose-derived stem cells (hADSC) when compared to non-stimulated cells in vitro. hADSC were exposed to continuous electrical stimulation with 1.7 V AC/20 Hz. After 24, 72 h and 7 days, cell number, cellular surface coverage and cell proliferation were assessed. In addition, cell cycle analysis was carried out after 3 and 7 days. After 24 h, no significant alterations were observed for stimulated cells. At day 3, stimulated cells showed a 4.5-fold increase in cell numbers, a 2.7-fold increase in cellular surface coverage and a significantly increased proliferation. Via cell cycle analysis, a significant increase in the G2/M phase was monitored for stimulated cells. Contrastingly, after 7 days, the non-stimulated group exhibited a 11-fold increase in cell numbers and a 4-fold increase in cellular surface coverage as well as a significant increase in cell proliferation. Moreover, the stimulated cells displayed a shift to the G1 and sub-G1 phase, indicating for metabolic arrest and apoptosis initiation. In accordance, continuous electrical stimulation of hADSC led to a significantly increased cell growth and proliferation after 3 days. However, longer stimulation periods such as 7 days caused an opposite result indicating initiation of apoptosis.
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http://dx.doi.org/10.3390/biomedicines8110482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695310PMC
November 2020

Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma: A pilot study.

Mol Clin Oncol 2020 Dec 21;13(6):88. Epub 2020 Oct 21.

Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, D-06120 Halle (Saale), Germany.

In various tumors, epidermal growth factor-receptor (EGFR) serves a role in tumorigenesis and has an impact on survival. Usually the EGF-receptor is located on the surface of the cell membrane and is involved in various signaling pathways. The dimerization of EGFR with other ErbB family proteins, such as HER2, is important for the tumor progression. Nevertheless, a second EGFR-associated signaling pathway appears to be important for tumor cells, which is cytoplasmic/nuclear EGFR. The present study examined the influence of membranous or cytoplasmic localized EGFR on the prognosis of patients with oral squamous cell carcinoma (OSCC). Slides from 45 OSCC tumor samples were stained against EGFR using immunohistochemistry and analysed by the Remmele score system. The association with histopathological parameters and survival data was analyzed. Cytoplasmatic EGFR localization was identified as an independent predictive biomarker for overall survival in the examined OSCC cohort according to multivariate Cox regression analysis. Positive cytoplasmatic EGFR staining was correlated with a higher risk of early death (RR=3.0; P=0.035), while membranous EGFR localization did not affect patient survival. To the best of our knowledge, the present study is the first study to demonstrate that cytoplasmatic-localized EGFR is an independent prognostic biomarker for the overall survival of patients with OSCC.
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http://dx.doi.org/10.3892/mco.2020.2158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642807PMC
December 2020

Complications or rather side effects? Quantification of patient satisfaction and complications after orthognathic surgery-a retrospective, cross-sectional long-term analysis.

Clin Oral Investig 2021 May 6;25(5):3315-3327. Epub 2020 Nov 6.

Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, University Medical Centre Mainz, Augustusplatz 2, 55131, Mainz, Germany.

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) 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.
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http://dx.doi.org/10.1007/s00784-020-03664-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060167PMC
May 2021

Clinical efficacy of an antibody-based detection system for human papilloma virus infection in oral squamous cell carcinoma.

Clin Oral Investig 2021 May 23;25(5):2837-2843. Epub 2020 Oct 23.

Department of Oral- and Maxillofacial Surgery - Plastic Surgery, University Medical Centre, Augustusplatz 2, 55131, Mainz, Germany.

Objectives: There is an increasing number of oral squamous cell carcinoma (OSCC) associated with HPV-16. However, p16 expression by immunohistochemistry as the current gold standard for a surrogate marker for virus infection reveals unsatisfying diagnostic accuracy. The aim of this study was to investigate a new rapid test for L1 antibody detection (Prevocheck®) and to validate its diagnostic performance.

Materials And Methods: In a prospective study, the HPV 16 association of all consecutive patients with an OSCC treated between 2015 and 2019 were analyzed by L1 seropositivity (via PrevoCheck®), p16 immunostaining, and partly multiplex PCR for subtype analysis.

Results: Overall (n = 107), p16 expression was positive in 17 cases (15.9%), and L1 antibody seropositivity in 7 cases (6.5%). In PCR analysis, two cases of HPV35 and 50 were found. Total HPV prevalence was 8.4% overall and 6.5% for HPV-16. An inferior diagnostic accuracy for HPV-16-associated OSCC in comparison to PrevoCheck® was revealed.

Conclusion: The rapid test for L1 antibodies showed an optimal sensitivity and specificity, positive and negative predictive value, and an overall diagnostic accuracy of 100%. However, HPV prevalence seems low in OSCC.

Clinical Relevance: L1 rapid test may represent an additional diagnostic staging method to detect HPV-16 association rather than p16 immunohistochemistry.
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http://dx.doi.org/10.1007/s00784-020-03601-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060226PMC
May 2021

Amplified morphogenetic and bone forming activity of amorphous versus crystalline calcium phosphate/polyphosphate.

Acta Biomater 2020 12 17;118:233-247. Epub 2020 Oct 17.

ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, GERMANY.

Amorphous Ca-phosphate (ACP) particles stabilized by inorganic polyphosphate (polyP) were prepared by co-precipitation of calcium and phosphate in the presence of polyP (15% [w/w]). These hybrid nanoparticles showed no signs of crystallinity according to X-ray diffraction analysis, in contrast to the particles obtained at a lower (5% [w/w]) polyP concentration or to hydroxyapatite. The ACP/15% polyP particles proved to be a suitable matrix for cell growth and attachment and showed pronounced osteoblastic and vasculogenic activity in vitro. They strongly stimulated mineralization of the human osteosarcoma cell line SaOS-2, as well as cell migration/microvascularization, as demonstrated in the scratch assay and the in vitro angiogenesis tube forming assay. The possible involvement of an ATP gradient, generated by polyP during tube formation of human umbilical vein endothelial cells, was confirmed by ATP-depletion experiments. In order to assess the morphogenetic activity of the hybrid particles in vivo, experiments in rabbits using the calvarial bone defect model were performed. The particles were encapsulated in poly(d,l-lactide-co-glycolide) microspheres. In contrast, to crystalline Ca-phosphate (containing only 5% [w/w] polyP) or to crystalline β-tricalcium phosphate, amorphous ACP/15% polyP particles caused pronounced osteoinductive activity already after a six-week healing period. The synthesis of new bone tissue was accompanied by an intense vascularization and an increased expression of mineralization/vascularization marker genes. The data show that amorphous polyP-stabilized ACP, which combines osteoinductive activity with the ability to act as a precursor of hydroxyapatite formation both in vitro and in vivo, is a promising material for bone regeneration.
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http://dx.doi.org/10.1016/j.actbio.2020.10.023DOI Listing
December 2020

In Vivo Modulation of Angiogenesis and Immune Response on a Collagen Matrix via Extracorporeal Shockwaves.

Int J Mol Sci 2020 Oct 14;21(20). Epub 2020 Oct 14.

Department of Oral- and Maxillofacial and Plastic Surgery, University Medical Center Mainz, Augustusplatz 2, 55131 Mainz, Germany.

The effective management of tissue integration and immunological responses to transplants decisively co-determines the success of soft and hard tissue reconstruction. The aim of this in vivo study was to evaluate the eligibility of extracorporeal shock wave therapy (ESWT) with respect to its ability to modulate angiogenesis and immune response to a collagen matrix (CM) for tissue engineering in the chorioallantoic membrane (CAM) assay, which is performed with fertilized chicken eggs. CM were placed on the CAM on embryonic development day (EDD) 7; at EDD-10, ESWT was conducted at 0.12 mJ/mm with 500 impulses each. One and four days later, angiogenesis represented by vascularized area, vessel density, and vessel junctions as well as HIF-1α and VEGF gene expression were evaluated. Furthermore, immune response (iNOS2, MMP-9, and MMP-13 via qPCR) was assessed and compared between ESWT- and non-ESWT-groups. At EDD-14, the vascularized area (+115% vs. +26%) and the increase in vessel junctions (+751% vs. +363%) were significantly higher in the ESWT-group. ESWT significantly increased MMP-9 gene expression at EDD-11 and significantly decreased MMP-13 gene expression at EDD-14 as compared to the controls. Using the CAM assay, an enhanced angiogenesis and neovascularization in CM after ESWT were observed. Furthermore, ESWT could reduce the inflammatory activity after a latency of four days.
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http://dx.doi.org/10.3390/ijms21207574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589066PMC
October 2020

Full-thickness tissue engineered oral mucosa for genitourinary reconstruction: A comparison of different collagen-based biodegradable membranes.

J Biomed Mater Res B Appl Biomater 2021 04 10;109(4):572-583. Epub 2020 Sep 10.

Department of Gynecology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Tissue engineering is a method of growing importance regarding clinical application in the genitourinary region. One of the key factors in successfully development of an artificially tissue engineered mucosa equivalent (TEOM) is the optimal choice of the scaffold. Collagen scaffolds are regarded as gold standard in dermal tissue reconstruction. Four distinct collagen scaffolds were evaluated for the ability to support the development of an organotypical tissue architecture. TEOMs were established by seeding cocultures of primary oral epithelial cells and fibroblasts on four distinct collagen membranes. Cell viability was assessed by MTT-assay. The 3D architecture and functionality of the tissue engineered oral mucosa equivalents were evaluated by confocal laser-scanning microscopy and immunostaining. Cell viability was reduced on the TissuFoil E® membrane. A multi-stratified epithelial layer was established on all four materials, however the TEOMs on the Bio-Gide® scaffold showed the best fibroblast differentiation, secretion of tenascin and fibroblast migration into the membrane. The TEOMs generated on Bio-Gide® scaffold exhibited the optimal cellular organization into a cellular 3D network. Thus, the Bio-Gide® scaffold is a suitable matrix for engineering of mucosa substitutes in vitro.
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http://dx.doi.org/10.1002/jbm.b.34724DOI Listing
April 2021

Peri-implant defect grafting with autogenous bone or bone graft material in immediate implant placement in molar extraction sites-1- to 3-year results of a prospective randomized study.

Clin Oral Implants Res 2020 Nov 22;31(11):1138-1148. Epub 2020 Sep 22.

Department of Oral and Maxillofacial Surgery - Plastic Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Germany.

Objectives: To evaluate the survival rate, the orobuccal bone resorption and stability of peri-implant hard and soft tissues following immediate implant placement of wide diameter implants in molar extraction sites and peri-implant defect grafting with autogenous bone (AB) or biphasic bone graft material (BBGM) with 1- to 3-year follow-up examinations.

Material And Methods: Fifty wide diameter implants were placed in 50 patients immediately into molar extraction sockets by a flapless approach. Peri-implant defect augmentation was performed randomized with either AB or BBGM. Primary outcome variable was implant survival. Marginal bone level changes, orobuccal width of the alveolar crest, probing depths, and implant success were considered as secondary parameters.

Results: One implant of the BBGM group was lost, 1 patient withdrew from the study (drop-out). The remaining 48 patients were still in function at a follow-up period up to 31 months after implant insertion. Interproximal marginal bone level regenerated from -7.5 mm to the level of the implant shoulder (AB + 0.38 mm, BBGM + 0.1 mm) at final follow-up. The width of the alveolar crest changed by -0.08 mm (AB) and +0.72 mm (BBGM) at 1 mm, -0.36 mm (AB) and +0.27 mm (BBGM) at 3 mm, -0.36 mm (AB) and +0.31 mm (BBGM) at 6 mm apical to implant shoulder level. Success rate was 87.5% in the AB and 56.3% in the BBGM group (p = .058).

Conclusions: Medium-term results prove a high survival rate, a favorable amount of bone generation in both groups and a low amount of orobuccal resorption in immediate molar implant insertion.
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http://dx.doi.org/10.1111/clr.13660DOI Listing
November 2020

Implant primary stability depending on protocol and insertion mode - an ex vivo study.

Int J Implant Dent 2020 Sep 3;6(1):49. Epub 2020 Sep 3.

Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Augustusplatz 2, 55131, Mainz, Germany.

Background: Dental implant primary stability is thought to be a fundamental prerequisite for the long-term survival and success. The aim of this study was to analyze the influence of protocol and insertion mode on dental implant stability ex vivo. One hundred and twenty implants were inserted either manually or machine-driven into porcine mandibles by a standard or over-dimensioned protocol. Dental implant stability was measured via resonance frequency analysis (RFA), insertion torque (IT), and torque out (TO).

Results: Statistically significant higher IT and TO values were seen after standard protocol insertion (p < 0.05), whereas manual and machine-driven insertion mode showed equivalent values.

Conclusions: The over-dimensioned protocol exceeded the primary stability values recommended for immediate implant insertion; therefore, it could be recommended as well.
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http://dx.doi.org/10.1186/s40729-020-00245-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468011PMC
September 2020

Effect of enamel matrix derivative liquid combined with synthetic bone substitute on bone regeneration in a rabbit calvarial model.

Clin Oral Investig 2021 Feb 1;25(2):547-554. Epub 2020 Aug 1.

Department of Oral & Maxillofacial Surgery, School of Dentistry, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

Objectives: This study aimed to verify the effectiveness of EMD-liquid in combination with a synthetic bone substitute in a rabbit calvarial model.

Material And Methods: Four 7-mm outer diameter circular slits were created in the calvaria of 10 New Zealand white rabbits, and polycarbonate cylinders were inserted into the slits. Two experimental groups were established: (1) EMD-liquid + bone substitute (Osteon III®; biphasic calcium phosphate (BCP), β-TCP/HA = 40:60) and (2) saline + bone substitute (Osteon III®; BCP). The cylinders were filled with saturated graft materials and covered with polycarbonate caps. Micro-CT and histomorphometric evaluation were conducted.

Results: In the histomorphometric analysis, new bone formation was significantly higher in the bone substitute (BS) + EMD-liquid group than in the BS only group at both 5 and 10 weeks (p < 0.01). There were statistically significant differences in the material area between the bone substitute and bone substitute + EMD-liquid groups at only 5 weeks (p < 0.05). The BS + EMD-liquid group demonstrated reduced material area to a greater extent. In micro-CT analysis, the BS + EMD-liquid group (27.04 ± 8.06 at 5 weeks, 28.49 ± 9.22 at 10 weeks) showed a significantly higher percentage of mineralized tissue volume at both 5 and 10 weeks (p < 0.05) than the BS only group.

Conclusion: EMD-liquid enhances new bone formation when combined with BCP bone substitute in an animal model. Moreover, the EMD-liquid + BS has significantly lesser material area than BS alone, indicating accelerated graft degradation. Further studies on types of graft materials are required to verify the effect of EMD-liquid and to optimize its regenerative potential.

Clinical Relevance: This study suggests that EMD-liquid may have beneficial effect on bone regeneration with synthetic bone substitute.
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http://dx.doi.org/10.1007/s00784-020-03473-4DOI Listing
February 2021

A cross-sectional survey of attitudes towards education in implant dentistry in the undergraduate dental curriculum.

Int J Implant Dent 2020 Jul 8;6(1):26. Epub 2020 Jul 8.

Universitätspoliklinik für Zahnärztliche Prothetik, Martin Luther Universität Halle-Wittenberg, Magdeburger Str. 16, 06112, Halle, Saale, Germany.

Background: An ongoing debate in dental education is whether implant dentistry, as a multidisciplinary domain, should be integrated into the undergraduate curriculum. The aim of the present study was to evaluate the perspectives of novices, clinical educators, and experienced dentists with regard to the importance of theoretical and practical implant dentistry teaching content in undergraduate dental education. The specific objective was to determine whether a consensus could be found concerning aspects of theoretical knowledge, implant position planning, implantation, prosthetic treatment procedures, postoperative care, and prerequisite experiences that should be provided in undergraduate dental education.

Results: A positive consensus existed in terms of theoretical education, assistance in surgical and prosthodontic procedures, implant planning and restoration in straightforward cases (i.e., posterior single crowns and bridges, overdentures on nonconnected implants), and postoperative care. A negative consensus existed for bone augmentation. Implantation was supported by novices (i.e., students and graduates). In addition, more experienced dentists were more likely to oppose implantation performed by undergraduates. The most preferred implantation method was implant insertion using a digitally fabricated drilling template, after surgical flap elevation.

Conclusions: Students and graduates preferred a comprehensive undergraduate education that included implant dentistry. Dentists working in private practice, and especially dentists working as university educators, were critical towards the integration of implant-related learning content into undergraduate education. The intention of medical education is to impart knowledge to students and to prepare them for life-long learning and continual professional development after graduation. Thus, an undergraduate dental curriculum that provides students a solid introduction and knowledge foundation in implant dentistry is recommended.
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http://dx.doi.org/10.1186/s40729-020-00224-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340723PMC
July 2020

DRH1 - a novel blood-based HPV tumour marker.

EBioMedicine 2020 Jun 11;56:102804. Epub 2020 Jun 11.

Department of Otorhinolaryngology-Head&Neck Surgery, General Hospital Ried im Innkreis, Ried, Austria.

Background: To date, no studies have successfully shown that a highly specific, blood-based tumour marker to detect clinically relevant HPV-induced disease could be used for screening, monitoring therapy response or early detection of recurrence. This study aims to assess the clinical performance of a newly developed HPV16-L1 DRH1 epitope-specific serological assay.

Methods: In a multi-centre study sera of 1486 patients (301 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, 12 HIV+ anal cancer patients, 80 HIV-positive patients, 29 Gardasil-9-vaccinees, 1064 healthy controls) were tested for human HPV16-L1 DRH1 antibodies. Analytical specificity was determined using WHO reference-sera for HPV16/18 and 29 pre- and post-immune sera of Gardasil-9-vaccinees. Tumour-tissue was immunochemically stained for HPV-L1-capsidprotein-expression.

Findings: The DRH1-competitive-serological-assay showed a sensitivity of 95% (95% CI, 772-999%) for HPV16-driven HNSCC, and 90% (95% CI, 555-997%) for HPV16-induced anal cancer in HIV-positives. Overall diagnostic specificity was 9946% for men and 9929% for women ≥ 30 years. After vaccination, antibody level increased from average 364 ng/ml to 37,500 ng/ml. During post-therapy-monitoring, HNSCC patients showing an antibody decrease in the range of 30-100% lived disease free over a period of up to 26 months. The increase of antibodies from 2750 to 12,000 ng/ml mirrored recurrent disease. We can also show that the L1-capsidprotein is expressed in HPV16-DNA positive tumour-tissue.

Interpretation: HPV16-L1 DRH1 epitope-specific antibodies are linked to HPV16-induced malignant disease. As post-treatment biomarker, the assay allows independent post-therapy monitoring as well as early diagnosis of tumour recurrence. An AUC of 096 indicates high sensitivity and specificity for early detection of HPV16-induced disease.

Funding: The manufacturer provided assays free of charge.
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http://dx.doi.org/10.1016/j.ebiom.2020.102804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300133PMC
June 2020
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