Calcium phosphate cements, primarily brushite cements, require the addition of setting retarders to ensure adequate processing time and processability. So far, citric acid has been the primary setting retarder used in this context. Due to the poor biocompatibility, it is crucial to explore alternative options for better processing. In recent years, the setting retarder phytic acid (IP6) has been increasingly investigated. This study investigates the biological behaviour of calcium phosphate cements with varying concentrations of IP6, in addition to their physical properties. Therefore cytocompatibility in vitro testing was performed using osteoblastic (MG-63) and osteoclastic (RAW 264.7 differentiated with RANKL) cells. We could demonstrate that the physical properties like the compressive strength of specimens formed with IP6 (brushite_IP6_5 = 11.2 MPa) were improved compared to the reference (brushite = 9.8 MPa). In osteoblast and osteoclast assays, IP6 exhibited significantly better cytocompatibility in terms of cell activity and cell number for brushite cements up to 11 times compared to the brushite reference. In contrast, the calcium-deficient hydroxyapatite (CDHA) cements produced similar results for IP6 (CDHA_IP6_0.25 = 27.0 MPa) when compared to their reference (CDHA = 21.2 MPa). Interestingly, lower doses of IP6 were found to be more effective than higher doses with up to 3 times higher. Additionally, IP6 significantly increased degradation in both passive and active resorption. For these reasons, IP6 is emerging as a strong new competitor to established setting retarders such as citric acid. These cements have potential applications in bone augmentation, the stabilisation of non-load bearing fractures (craniofacial), or the cementation of metal implants. Graphical Abstract

Bone defects resulting from trauma, diseases, or surgical procedures pose significant challenges in the field of oral and maxillofacial surgery. The development of effective bone substitute materials that promote bone healing and regeneration is crucial for successful clinical outcomes. Calcium phosphate cements (CPCs) have emerged as promising candidates for bone replacement due to their biocompatibility, bioactivity, and ability to integrate with host tissues. However, there is a continuous demand for further improvements in the mechanical properties, biodegradability, and bioactivity of these materials. Dual setting of cements is one way to improve the performance of CPCs. Therefore, silicate matrices can be incorporated in these cements. Silicate-based materials have shown great potential in various biomedical applications, including tissue engineering and drug delivery systems. In the context of bone regeneration, silicate matrices offer unique advantages such as improved mechanical stability, controlled release of bioactive ions, and enhanced cellular responses. Comprehensive assessments of both the material properties and biological responses of our samples were conducted. Cytocompatibility was assessed through in vitro testing using osteoblastic (MG-63) and osteoclastic (RAW 264.7) cell lines. Cell activity on the surfaces was quantified, and scanning electron microscopy (SEM) was employed to capture images of the RAW cells. In our study, incorporation of tetraethyl orthosilicate (TEOS) in dual-curing cements significantly enhanced physical properties, attributed to increased crosslinking density and reduced pore size. Higher alkoxysilyl group concentration improved biocompatibility by facilitating greater crosslinking. Additionally, our findings suggest citrate’s potential as an alternative retarder due to its positive interaction with the silicate matrix, offering insights for future dental material research. This paper aims to provide an overview of the importance of silicate matrices as modifiers for calcium phosphate cements, focusing on their impact on the mechanical properties, setting behaviour, and biocompatibility of the resulting composites.

Although inhibitors targeting the PD1/PD-L1 immune checkpoint are showing comparably good outcomes, a significant percentage of head and neck squamous cell carcinoma (HNSCC) patients do not respond to treatment. Apart from using different treatment strategies, another possibility would be to target other immune checkpoints operating in these non-responding tumors. To obtain an overview of which checkpoint ligands are expressed on HNSCC tumor cells and if these ligands are affected by HGF/MET signaling, we used mRNA sequencing and antibody-based techniques for identifying checkpoint ligands in six HNSCC tumor cell lines. Furthermore, we compared our results to mRNA sequencing data. From the checkpoint ligands we investigated, VISTA was expressed the highest at the RNA level and was also the most ubiquitously expressed. PD-L2 and B7-H3 were expressed comparably lower and were not present in all cell lines to the same extent. B7-H4, however, was only detectable in the Detroit 562 cell line. Concerning the effect of HGF on the ligand levels, PD-L2 expression was enhanced with HGF stimulation, whereas other checkpoint ligand levels decreased with stimulation. B7-H4 levels in the Detroit 562 cell line drastically decreased with HGF stimulation. This is of interest because both the checkpoint ligand and the growth factor are reported to be connected to epithelial–mesenchymal transition in the literature.

Background and Objective The combination of ampicillin (AMP) together with sulbactam (SBC) is a widely used choice for infection prophylaxis in the context of numerous surgical procedures, especially those performed in the field of maxillofacial surgery. Since the pharmacokinetic behavior of these two substances in body tissues is not known in detail owing to sparse tissue data in the literature, the aim of this work was to develop a physiologically based pharmacokinetic (PBPK) model that can predict the concentration versus time courses of AMP and SBC after intravenous administration in plasma, especially bone tissue. Furthermore, the effectiveness of an established prophylaxis regimen based on the developed PBPK model was to be evaluated. Methods A PBPK model for middle-aged and elderly populations was created using PK-Sim^® software. A total of nine human clinical studies which included data from plasma, lung, skin, and bone tissue were utilized to verify the model. In addition to the physicochemical properties and ADME (Absorption, Distribution, Metabolism, and Excretion) characteristics of AMP and SBC, the measured drug concentrations from the clinical studies were used for development and validation. The performance of the model was evaluated on the basis of established fold error acceptance criteria for selected pharmacokinetic parameters. Here, the model predictions were compared with the observed values. Results The final PBPK model for AMP and SBC could well describe the measured mean concentrations in plasma and in the different body tissues, as these fell within the predicted 5th-95th percentile range for the most part. This applies to 97% of the AMP and 88% of the SBC measurements. Exactly 81% of the fold error values of the pharmacokinetic parameters are within the twofold acceptance criterion. Overall, the average fold errors for the evaluated pharmacokinetic parameters were within the range of 1.01–1.43. Conclusions In this work, we present the first PBPK model that simultaneously predicts AMP and SBC in plasma and various tissues. In addition to observed plasma data, the model was also developed and verified with experimentally measured data from the above-mentioned tissues. This allowed a significant limitation of previous PBPK models to be overcome. The effectiveness of established prophylaxis regimes is demonstrated through our model, whereby it must be assumed, owing to measured data for bone tissue, that some individuals do not reach the target values for adequate prophylaxis.

Background: Patient-specific splints have become an integral component of virtual surgical planning in orthognathic surgery. However, transferring the virtually planned condylar position into the intraoperative setting remains technically challenging and typically requires labor-intensive manual modification of splint geometries. The aim of this study was to develop and describe an open-source Blender add-on that automates the generation of patient-specific splint extensions for condyle positioning and to evaluate its technical feasibility in a proof-of-concept clinical setting. Methods: A Python-based add-on for the open-source 3D modelling software Blender was developed to automate the generation of condyle-positioning splint extensions from stereolithography (STL) models exported by a commercial virtual surgical planning system. The software architecture and processing pipeline comprise facilitated data import, coordinate normalization, extension generation, Boolean processing, optional manual refinement, and STL export for additive manufacturing. The workflow was applied in three patients undergoing bilateral sagittal split osteotomy. Postoperative correspondence between the planned and achieved mandibular positions was assessed using translational and rotational transformation parameters together with qualitative surface distance heatmaps provided by the planning software. Results: The proposed add-on successfully generated patient-specific splint extensions in all three proof-of-concept cases while automating manual modelling steps. All splints were successfully manufactured and applied intraoperatively without redesign. Postoperative evaluation demonstrated good agreement between the virtually planned and achieved mandibular positions, with only small translational and rotational deviations. Descriptive statistical analysis supported the technical feasibility and reproducibility of the proposed workflow. Conclusions: The presented open-source Blender add-on provides a reproducible and extensible workflow for automated generation of patient-specific condyle-positioning splint extensions. The proposed approach successfully integrates virtual surgical planning with additive manufacturing and demonstrates technical feasibility in a proof-of-concept clinical setting. The software establishes a foundation for future validation studies in larger patient cohorts and illustrates the potential of open-source tools to improve transparency, reproducibility, and accessibility in digital orthognathic surgery workflows.