Mass Spectrometry-Based Proteomics of Poly(methylmethacrylate)-Embedded Bone.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely employed technique in proteomics research for studying the proteome biology of various clinical samples. Hard tissues, such as bone and teeth, are routinely preserved using synthetic poly(methyl methacrylate) (PMMA) embedding resins that enable histological, immunohistochemical, and morphological examination. However, the suitability of PMMA-embedded hard tissues for large-scale proteomic analysis remained unexplored. This study is the first to report on the feasibility of PMMA-embedded bone samples for LC-MS/MS analysis. Conventional workflows yielded merely limited coverage of the bone proteome. Using advanced strategies of prefractionation by high-pH reversed-phase liquid chromatography in combination with isobaric tandem mass tag labeling resulted in proteome coverage exceeding 1000 protein identifications. The quantitative comparison with cryopreserved samples revealed that each sample preparation workflow had a distinct impact on the proteomic profile. However, workflow replicates exhibited a high reproducibility for PMMA-embedded samples. Our findings further demonstrate that decalcification prior to protein extraction, along with the analysis of solubilization fractions, is not preferred for PMMA-embedded bone. The biological applicability of the proposed workflow was demonstrated using samples of human PMMA-embedded alveolar bone and the iliac crest, which revealed anatomical site-specific proteomic profiles. Overall, these results establish a crucial foundation for large-scale proteomics studies contributing to our knowledge of bone biology.

Advancements in diagnosing oral potentially malignant disorders: leveraging Vision transformers for multi-class detection.

OBJECTIVES: Diagnosing oral potentially malignant disorders (OPMD) is critical to prevent oral cancer. This study aims to automatically detect and classify the most common pre-malignant oral lesions, such as leukoplakia and oral lichen planus (OLP), and distinguish them from oral squamous cell carcinomas (OSCC) and healthy oral mucosa on clinical photographs using vision transformers. METHODS: 4,161 photographs of healthy mucosa, leukoplakia, OLP, and OSCC were included. Findings were annotated pixel-wise and reviewed by three clinicians. The photographs were divided into 3,337 for training and validation and 824 for testing. The training and validation images were further divided into five folds with stratification. A Mask R-CNN with a Swin Transformer was trained five times with cross-validation, and the held-out test split was used to evaluate the model performance. The precision, F1-score, sensitivity, specificity, and accuracy were calculated. The area under the receiver operating characteristics curve (AUC) and the confusion matrix of the most effective model were presented. RESULTS: The detection of OSCC with the employed model yielded an F1 of 0.852 and AUC of 0.974. The detection of OLP had an F1 of 0.825 and AUC of 0.948. For leukoplakia the F1 was 0.796 and the AUC was 0.938. CONCLUSIONS: OSCC were effectively detected with the employed model, whereas the detection of OLP and leukoplakia was moderately effective. CLINICAL RELEVANCE: Oral cancer is often detected in advanced stages. The demonstrated technology may support the detection and observation of OPMD to lower the disease burden and identify malignant oral cavity lesions earlier.

Donor site morbidity after computer assisted surgical reconstruction of the mandible using deep circumflex iliac artery grafts: a cross sectional study.

BACKGROUND: Computer Assisted Design and Computer Assisted Manufacturing (CAD/CAM) have revolutionized oncologic surgery of the head and neck. A multitude of benefits of this technique has been described, but there are only few reports of donor site comorbidity following CAD/CAM surgery. METHODS: This study investigated comorbidity of the hip following deep circumflex iliac artery (DCIA) graft raising using CAD/CAM techniques. A cross-sectional examination was performed to determine range of motion, muscle strength and nerve disturbances. Furthermore, correlations between graft volume and skin incision length with postoperative donor site morbidity were assessed using Spearman's rank correlation, linear regression and analysis of variance (ANOVA). RESULTS: Fifteen patients with a mean graft volume of 21.2 ± 5.7 cm3 and a mean incision length of 228.0 ± 30.0 mm were included. Patients reported of noticeable physical limitations in daily life activities (12.3 ± 11.9 weeks) and athletic activities (38.4 ± 40.0 weeks in mean) following surgery. Graft volume significantly correlated with the duration of the use of walking aids (R = 0.57; p = 0.033) and impairment in daily life activities (R = 0.65; p = 0.012). The length of the scar of the donor-site showed a statistically significant association with postoperative iliohypogastric nerve deficits (F = 4.4, p = 0.037). Patients with anaesthaesia of a peripheral cutaneous nerve had a larger mean scar length (280 ± 30.0 mm) than subjects with hypaesthesia (245 ± 10.1 mm) or no complaints (216 ± 27.7 mm). CONCLUSIONS: Despite sophisticated planning options in modern CAD/CAM surgery, comorbidity of the donor site following  iliac graft harvesting is still a problem. This study is the first to investigate comorbidity after DCIA graft raising in a patient group treated exclusively with CAD/CAM techniques. The results indicate that a minimal invasive approach in terms of small graft volumes and small skin incisions could help to reduce postoperative symptomatology. Trial registration Retrospectively registered at the German Clinical Trials Register (DRKS-ID: DRKS00029066); registration date: 23/05/2022.

Reconstruction of dental roots for implant planning purposes: a retrospective computational and radiographic assessment of single-implant cases.

PURPOSE: The aim of the study was to assess the deviation between clinical implant axes (CIA) determined by a surgeon during preoperative planning and reconstructed tooth axes (RTA) of missing teeth which were automatically computed by a previously introduced anatomical SSM. METHODS: For this purpose all available planning datasets of single-implant cases of our clinic, which were planned with coDiagnostix Version 9.9 between 2018 and 2021, were collected for retrospective investigation. Informed consent was obtained. First, the intraoral scans of implant patients were annotated and subsequently analyzed using the SSM. The RTA, computed by the SSM, was then projected into the preoperative planning dataset. The amount and direction of spatial deviation between RTA and CIA were then measured. RESULTS: Thirty-five patients were implemented. The mean distance between the occlusal entry point of anterior and posterior implants and the RTA was 0.99 mm ± 0.78 mm and 1.19 mm ± 0.55, respectively. The mean angular deviation between the CIA of anterior and posterior implants and the RTA was 12.4° ± 3.85° and 5.27° ± 2.97° respectively. The deviations in anterior implant cases were systematic and could be corrected by computing a modified RTA (mRTA) with decreased deviations (0.99 mm ± 0.84 and 4.62° ± 1.95°). The safety distances of implants set along the (m)RTA to neighboring teeth were maintained in 30 of 35 cases. CONCLUSION: The RTA estimated by the SSM revealed to be a viable implant axis for most of the posterior implant cases. As there are natural differences between the anatomical tooth axis and a desirable implant axis, modifications were necessary to correct the deviations which occurred in anterior implant cases. However, the presented approach is not applicable for clinical use and always requires manual optimization by the planning surgeon.

A content-aware chatbot based on GPT 4 provides trustworthy recommendations for Cone-Beam CT guidelines in dental imaging.

OBJECTIVES: To develop a content-aware chatbot based on GPT-3.5-Turbo and GPT-4 with specialized knowledge on the German S2 Cone-Beam CT (CBCT) dental imaging guideline and to compare the performance against humans. METHODS: The LlamaIndex software library was used to integrate the guideline context into the chatbots. Based on the CBCT S2 guideline, 40 questions were posed to content-aware chatbots and early career and senior practitioners with different levels of experience served as reference. The chatbots' performance was compared in terms of recommendation accuracy and explanation quality. Chi-square test and one-tailed Wilcoxon signed rank test evaluated accuracy and explanation quality, respectively. RESULTS: The GPT-4 based chatbot provided 100% correct recommendations and superior explanation quality compared to the one based on GPT3.5-Turbo (87.5% vs. 57.5% for GPT-3.5-Turbo; P = .003). Moreover, it outperformed early career practitioners in correct answers (P = .002 and P = .032) and earned higher trust than the chatbot using GPT-3.5-Turbo (P = 0.006). CONCLUSIONS: A content-aware chatbot using GPT-4 reliably provided recommendations according to current consensus guidelines. The responses were deemed trustworthy and transparent, and therefore facilitate the integration of artificial intelligence into clinical decision-making.

Comparison of the 3D-microstructure of human alveolar and fibula bone in microvascular autologous bone transplantation: a synchrotron radiation µ-CT study.

Introduction: Autologous bone transplantation is successfully used in reconstructive surgery of large/critical-sized bone defects, whereby the microvascular free fibula flap is still regarded as the gold standard for the reconstruction of such defects in the head and neck region. Here, we report the morphological and lacunar properties of patient-paired bone samples from eight patients from the jaw (AB; recipient site) and the fibula (FB; donor site) on the micron length-scale using Synchrotron µ-CT. Insights into differences and similarities between these bone structures could offer a better understanding of the underlying mechanism for successful surgical outcomes and might clear the path for optimized, nature-inspired bone scaffold designs. Methods: Spatial vessel-pore arrangements, bone morphology, fluid-simulation derived permeability tensor, osteocyte lacunar density, and lacunar morphology are compared. Results: The orientation of the vessel system indicates a homogenous vessel orientation for AB and FB. The average mineral distance (50%) to the closest vessel boundary is higher in AB than in FB (the mean is 96 µm for AB vs. 76 µm for FB; p = 0.021). Average osteocyte lacunar density is found to be higher in AB than in FB (mean 22,874 mm3 vs. 19,376 mm3 for FB; p = 0.038), which might compensate for the high distance from the mineral to the nearest vessel. No significant differences in lacunar volume are found between paired AB and FB. Discussion: A comparable vessel network and similar distribution of vessel porosity between AB and FB may allow the FB graft to exhibit a high regeneration potential when connected to AB, and this might correlate with a high osteoinductive and osteoconductive potential of FB when connected to AB. Since widely used and potent synthetic bone grafts exist, new insight into the bone structure of well-established autologous bone grafts, such as the free fibula flap, could help to improve the performance of such materials and therefore the design of 3D scaffolds.

Impurities in commercial titanium dental implants - A mass and optical emission spectrometry elemental analysis.

OBJECTIVE: Titanium (Ti) is considered bioinert and is still regarded as the "gold standard" material for dental implants. However, even 'commercial pure' Ti will contain minor fractions of elemental impurities. Evidence demonstrating the release of Ti ions and particles from 'passive' implant surfaces is increasing and has been attributed to biocorrosion processes which may provoke immunological reactions. However, Ti observed in peri-implant tissues has been shown to be co-located with elements considered impurities in biomedical alloys. Accordingly, this study aimed to quantify the composition of impurities in commercial Ti dental implants. METHODS: Fifteen commercial titanium dental implant systems were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). RESULTS: The elemental composition of implants manufactured from commercially pure grades of Ti, Ti-6Al-4V, and the TiZr alloy (Roxolid) conformed to the respective ISO/ASTM standards or manufacturers´ data (TiZr/Roxolid). However, all implants investigated included exogenous metal contaminants including Ni, Cr, Sb, and Nb to a variable extent. Other contaminants detected in a fraction of implants included As and the radionuclides U-238 and Th-232. SIGNIFICANCE: Although all Ti implant studies conformed with their standard compositions, potentially allergenic, noxious metals and even radionuclides were detected. Since there are differences in the degree of contamination between the implant systems, a certain impurity fraction seems technically avoidable. The clinical relevance of these findings must be further investigated, and an adaptation of industry standards should be discussed.

Feasibility of Implant Strain Measurement for Assessing Mandible Bone Regeneration.

Nonunion is one of the most dreaded complications after operative treatment of mandible fractures or after mandible reconstruction using vascularized and non-vascularized bone grafts. Often diagnosis is made at advanced stage of disease when pain or complications occur. Devices that monitor fracture healing and bone regeneration continuously are therefore urgently needed in the craniomaxillofacial area. One promising approach is the strain measurement of plates. An advanced prototype of an implantable strain measurement device was tested after fixation to a locking mandible reconstruction plate in multiple compression experiments to investigate the potential functionality of strain measurement in the mandibular region. Compression experiments show that strain measurement devices work well under experimental conditions in the mandibular angle and detect plate deformation in a reliable way. For monitoring in the mandibular body, the device used in its current configuration was not suitable. Implant strain measurement of reconstruction plates is a promising methodical approach for permanent monitoring of bone regeneration and fracture healing in the mandible. The method helps to avoid or detect complications at an early point in time after operative treatment.

A Novel Method for Digital Reconstruction of the Mucogingival Borderline in Optical Scans of Dental Plaster Casts.

Adequate soft-tissue dimensions have been shown to be crucial for the long-term success of dental implants. To date, there is evidence that placement of dental implants should only be conducted in an area covered with attached gingiva. Modern implant planning software does not visualize soft-tissue dimensions. This study aims to calculate the course of the mucogingival borderline (MG-BL) using statistical shape models (SSM). Visualization of the MG-BL allows the practitioner to consider the soft tissue supply during implant planning. To deploy an SSM of the MG-BL, healthy individuals were examined and the intra-oral anatomy was captured using an intra-oral scanner (IOS). The empirical anatomical data was superimposed and analyzed by principal component analysis. Using a Leave-One-Out Cross Validation (LOOCV), the prediction of the SSM was compared with the original anatomy extracted from IOS. The median error for MG-BL reconstruction was 1.06 mm (0.49-2.15 mm) and 0.81 mm (0.38-1.54 mm) for the maxilla and mandible, respectively. While this method forgoes any technical work or additional patient examination, it represents an effective and digital method for the depiction of soft-tissue dimensions. To achieve clinical applicability, a higher number of datasets has to be implemented in the SSM.

Elemental analysis of commercial zirconia dental implants - Is "metal-free" devoid of metals?

OBJECTIVES: The interest in ceramic dental implants made of yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) or alumina toughened zirconia (ATZ) has increased in recent years. However, in the light of aging, corrosion, and potential impurities of zirconia ceramics, the material composition of these implants and the associated term "metal-free" is persistently questioned. Thus, the present study aimed to conduct an elemental analysis of commercial zirconia dental implants to specify their elemental composition and to identify contaminants. METHODS: Nine commercial zirconia dental implant systems and corresponding material samples were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES). RESULTS: While the elemental composition was dominated by the main components Zr, Y and Al (in ATZ samples), all investigated samples contained impurities with Hf and contamination with alkali and alkali earth elements (Na, K, Mg, Ca), essential trace elements (e.g. Fe, Cu, Zn) but also potentially noxious metal elements (e.g. Ni, Cr). Furthermore, ultra-trace level contamination with the radionuclides U-238 and Th-232 was found in the majority of samples. SIGNIFICANCE: The results indicate that, although all the investigated Y-TZP and ATZ dental implants meet the currently relevant ISO standards and manufacturer's specifications, from an elemental point of view, they are not devoid of metals. Due to the lack of a universal definition and thresholds for the term "metal-free", the question of whether the examined zirconia dental implants can be holistically classified as "metal-free" or not remains a controversial, philosophical one.