Performance of cone-beam computed tomography (CBCT) in comparison to conventional computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone invasion in oral squamous cell cancer (OSCC): a prospective study.

BACKGROUND: Oral squamous carcinoma (OSCC) is often diagnosed at late stages and bone erosion or invasion of the jawbone is frequently present. Computed tomography (CT) and magnetic resonance imaging (MRI) are known to have high diagnostic sensitivities, specificities, and accuracies in detecting these bone affections in patients suffering from OSCC. To date, the existing data regarding the impact of cone-beam computed tomography (CBCT) have been weak. Therefore, this study aimed to investigate whether CBCT is a suitable tool to detect bone erosion or invasion in patients with OSCC. METHODS: We investigated in a prospective trial the impact of CBCT in the diagnosis of bone erosion or invasion in patients with OSCC who underwent surgery. Every participant received a CBCT, CT, and MRI scan during staging. Imaging modalities were evaluated by two specialists in oral and maxillofacial surgery (CBCT) and two specialists in radiology (CT and MRI) in a blinded way, to determine whether a bone affection was present or not. Reporting used the following 3-point system: no bony destruction ("0"), cortical bone erosion ("1"), or medullary bone invasion ("2"). Histological examination or a follow-up served to calculate the sensitivities, specificities, and accuracies of the imaging modalities. RESULTS: Our results revealed high diagnostic sensitivities (95.6%, 84.4%, and 88.9%), specificities (87.0%, 91.7%, and 91.7%), and accuracies (89.5%, 89.5%, and 90.8%) for CBCT, CT, and MRI. A pairwise comparison found no statistical difference between CBCT, CT, and MRI. CONCLUSION: Our data support the routine use of CBCT in the diagnosis of bone erosion and invasion in patients with OSCC as diagnostic accuracy is equal to CT and MRI, the procedure is cost-effective, and it can be performed during initial contact with the patient.

PKM2 Modulation in Head and Neck Squamous Cell Carcinoma.

The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease.

Protein-Based Oncopanel as Addition to Target Sequencing in Head and Neck Squamous Cell Carcinoma to Individualize Treatment Decisions.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers and patients have limited therapy options if primary treatment fails. Therefore, additional information about the biology of the tumor is essential. Here we performed a feasibility study of concurrently applying two precision diagnostic tools in a consecutive series of HNSCC patients. We analyzed tumor samples of 31 patients using a genomic (oncomine) and a proteomic, immunohistochemical approach (oncopanel) and compared the result, also in the focus on their overlapping therapeutical targets. We found no strong correlation between the two approaches and observed a higher proportion of marker expression for the immunohistochemical panel. However, both panels show in our HNSCC cohort distinct patterns with druggable targets. The data suggest that both approaches complement one another and can be applied side-by-side to identify the best targets for the development of individual treatment options for HNSCC patients.

HGF-Induced PD-L1 Expression in Head and Neck Cancer: Preclinical and Clinical Findings.

Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.

The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Methigh-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.

The Selection of NFκB Inhibitors to Block Inflammation and Induce Sensitisation to FasL-Induced Apoptosis in HNSCC Cell Lines Is Critical for Their Use as a Prospective Cancer Therapy.

Inflammation is a central aspect of tumour biology and can contribute significantly to both the origination and progression of tumours. The NFκB pathway is one of the most important signal transduction pathways in inflammation and is, therefore, an excellent target for cancer therapy. In this work, we examined the influence of four NFκB inhibitors-Cortisol, MLN4924, QNZ and TPCA1-on proliferation, inflammation and sensitisation to apoptosis mediated by the death ligand FasL in the HNSCC cell lines PCI1, PCI9, PCI13, PCI52 and SCC25 and in the human dermal keratinocyte cell line HaCaT. We found that the selection of the inhibitor is critical to ensure that cells do not respond by inducing counteracting activities in the context of cancer therapy, e.g., the extreme IL-8 induction mediated by MLN4924 or FasL resistance mediated by Cortisol. However, TPCA1 was qualified by this in vitro study as an excellent therapeutic mediator in HNSCC by four positive qualities: (1) proliferation was inhibited at low µM-range concentrations; (2) TNFα-induced IL-8 secretion was blocked; (3) HNSCC cells were sensitized to TNFα-induced cell death; and (4) FasL-mediated apoptosis was not disrupted.

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - update 2018.

Merkel cell carcinoma (MCC, ICD-O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross-sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence-free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD-1/PD-L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup.

MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer.

OBJECTIVE: The objective of this study is to investigate the roles of melanoma-associated antigens (MAGEs) in the cisplatin treatment of head and neck cancer. MATERIALS AND METHODS: We assessed the efficacy of cisplatin in a set of four head and neck cancer cell lines using a crystal violet assay. The MAGE-A expression in all cell lines was measured with RT-qPCR. The correlation between MAGE-A expression and cisplatin efficacy was investigated using Spearman's correlation analysis. Furthermore, we established a cell line with stable overexpression of MAGE-A11 and determined influence on proliferation, cisplatin efficacy and cell apoptosis. In this cell line, the effects of cisplatin were assessed using either crystal violet assays or flow cytometry (Annexin V). RESULTS: For MAGE-A11, we observed the highest correlation (r = 1.000, p = 0.0417) with low cisplatin efficacy. Stable overexpression of MAGE-A11 resulted in no changes in proliferation, but in lower cisplatin cytotoxicity and lower rates of apoptosis. Also, mouse double minute 2 homolog (MDM2) expression was induced by MAGE-A11 overexpression. CONCLUSION: We provide evidence that MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer. CLINICAL RELEVANCE: Our study underscores the negative predictive role of MAGE-A11 expression in head and neck cancer.

Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and Treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive tumor that often occurs in the head and neck region. Because of these features, the classifications and diagnostic and treatment regimens are frequently modified. Especially in the anatomically complex head and neck region, it is crucial to be aware of the current recommendations for diagnostics and treatment of MCC to ensure appropriate treatment. This overview aims to summarize the currently available literature. METHODS: The authors reviewed the relevant literature and international guidelines for MCC from 2012 to 2017 with respect to epidemiology and prognosis, diagnostic procedures and imaging, surgery, radiation, systemic treatment, and aftercare. These results were compared with existing guidelines, some of them current, and recommendations were derived. RESULTS: Marked developments in imaging have resulted in an increased use of functional imaging. The surgical concepts have changed regarding safety margins and the use of sentinel node biopsies. In systemic treatment, a move from conventional agents toward immuno-oncology can be observed. CONCLUSIONS: For staging, it is important to be as exact as possible using functional imaging (e.g., positron emission tomography/computed tomography scan), especially in the head and neck area with its complex lymph drainage. This often plays an especially important role in early stages of the tumor, when the resection margin can be reduced to preserve the organ. Aftercare also should include functional imaging. In an advanced, metastatic stage, immuno-oncology (PD-1, PD-L1, CTLA-4) is superior to the previous methods of systemic treatment.

The prognostic value of GLUT-1 staining in the detection of malignant transformation in oral mucosa.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common tumor entity worldwide. Unfortunately, the multimodal treatment consisting of surgery, radiation, and chemotherapy does not show the desired efficacy. The intent of this study was to evaluate the sensitivity and specificity of an oral brush biopsy in combination with glucose transporter (GLUT)-1 staining in identifying premalignant and malignant lesions. METHODS: A total of 72 patients were included in the study, divided into four diagnostic subgroups (24 healthy, 15 carcinoma, 18 leukoplakia, 15 oral lichen planus). Oral brush biopsies were taken and analyzed for GLUT-1 expression by immunocytologic staining. Incisional biopsy served as the gold standard. RESULTS: Twelve (80 %) of the 15 carcinomas, nine (50 %) of the 18 leukoplakia, nine (60 %) of the 15 oral lichen planus, and none of the healthy specimens stained positive for GLUT-1. This resulted in a sensitivity rate of 80 % and a specificity rate of 68.42 %. Diagnostic accuracy was 70.83 % based on the correct diagnoses in 51 of 72 patients. CONCLUSION: An oral brush biopsy can easily be performed throughout the entire oral cavity, is noninvasive, and shows high sensitivity and specificity rates with conventional cytology or computer-assisted analysis. CLINICAL RELEVANCE: The significance of GLUT-1-specific staining with an oral brush biopsy is more limited than expected but could be used as an additional tool in detecting malignant transformation in the oral cavity.

Perception of children's faces with unilateral coronal synostosis--an eye-tracking investigation.

PURPOSE: Premature unilateral coronal craniosynostosis results in distinctive cranial and facial abnormalities of varying severity, including orbital dystopia and an abnormal head shape. As the face is affected, these children may encounter stigmatization. To avoid this scenario, many parents elect for their child to undergo surgical correction. Laypeople's perception of children with either untreated or treated unilateral coronal craniosynostosis (UCS) has not yet been objectively evaluated. METHODS: This study introduces eye tracking as an objective instrument in order to evaluate the perception of 14 children with coronal synostosis, both pre- and postoperatively. Age-matched healthy children served as a control group. Using standardized photos, the involuntary eye movements and the fixations of 30 unaffected laypeople were evaluated. RESULTS: In the untreated children, whose faces were characterized by striking orbital dystopia, the eyes drew more attention than those of the healthy children. The results of our study demonstrate that the operative correction of unilateral coronal synostosis results in the normalization of the asymmetry of the fronto-orbital region, whereas the C-shaped deformity of the midface, which is not addressed via surgery, subsequently attracts more attention. CONCLUSION: Eye tracking objectively evaluates both the perception of craniofacial abnormalities and the extent of the approximation of normality after surgical correction. We introduce eye tracking as an objective measurement tool for craniofacial abnormalities for the first time.

Erlotinib and gefitinib responsiveness in head and neck cancer cell lines--a comparing analysis with cetuximab.

OBJECTIVE: The objective of this study is to examine the efficacy of erlotinib and gefitinib with respect to epidermal growth factor (EGF) and cetuximab response in head and neck cancer cell lines. MATERIALS AND METHODS: Five human head and neck carcinoma cell lines were treated with EGF, cetuximab, erlotinib, and gefitinib, and the effects were measured with a crystal violet assay. The efficacies of cetuximab, erlotinib, and gefitinib in clinically relevant concentrations were statistically analyzed. The expression of the epidermal growth factor receptor (EGFR) and phosphorylation patterns were detected with fluorescence-activated cell sorting (FACS) analysis and western blot analysis. The endogenous production of EGF by the cells was detected with an enzyme-linked immunosorbent assay. Finally, EGFR, KRAS, BRAF, and PI3K mutation analyses were performed. RESULTS: All of the cell lines had a poor or no response to EGF but exhibited distinct EGFR phosphorylation and EGFR expression. Compared to cetuximab, erlotinib and gefitinib demonstrated a greater impact on the majority of the cell lines. The only cell line that showed a concentration-dependent behavior toward EGF and strong EGFR phosphorylation was entirely resistant to cetuximab, erlotinib, and gefitinib. The production of EGF in all cell lines was very low. Mutational analysis of all cell lines revealed wild-type EGFR, KRAS, BRAF, and PI3K. CONCLUSIONS: The prediction of anti-EGFR treatment cannot be based on responsiveness to EGF or EGFR activation. CLINICAL RELEVANCE: Erlotinib and gefitinib show good response in EGF-independent cell lines and might be useful drugs in tumors that are less responsive to cetuximab.

Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide. Unfortunately, recent drug developments in other fields of oncology have yielded no efficacy in the treatment of oral squamous cell carcinoma. As a new starting point, we investigated the impact of Fas ligand (FasL) and the SMAC-mimetic compound LCL161 in mono- and combination treatment in HNSCC cell lines. METHODS: Five different cell lines of HNSCC were treated with FasL and LCL161 in mono- and combination treatment. Cytotoxicity was measured via a crystal violet assay. The cell lines were characterized for CD95 (FasL receptor) expression via flow cytometry. The degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) was detected via Western blot. RESULTS: Incubation with FasL led to a significant decrease in three out of five cell lines. Combination treatment with LCL161 enhanced cytotoxicity significantly. Two cell lines were FasL resistant, but one of them could be resensitized with LCL161. In all cell lines, Western blot analysis showed degradation of cIAP1 after LCL161 application. However, one cell line showed only minor vulnerability to the FasL and LCL161 combination. CONCLUSION: This is the first study investigating combination treatment of FasL and LCL161 in head and neck cancer cell lines. Pro-apoptotic effects of the combination were detected in the majority of the cell lines. Interestingly, one of two FasL-resistant cell lines was sensitive to the combination therapy with FasL and LCL161. CLINICAL RELEVANCE: SMAC-mimetic compounds show promising results in the treatment of other tumor entities in vitro and might be useful drugs to improve HNSCC therapy.

Diagnostic features of prematurely fused cranial sutures on plain skull X-rays.

PURPOSE: The characteristic features of prematurely fused craniosynostosis in plain radiographs have already been described in literature, but there is no clinical trial investigating the individual features of every single form of craniosynostosis. We described suture-specific characteristics as well as its frequency of appearance in plain radiographs in every different form of craniosynostosis. Intraoperative findings served as control to confirm the diagnosis. METHODS: One hundred twenty-seven children with prematurely fused cranial sutures who underwent a skull X-ray from 2008 to 2012 were investigated in the present study. In detail, 34 children with frontal, 60 with sagittal, 13 with unilateral and 14 with bilateral coronal synostosis and 3 with unilateral lambdoid craniosynostosis as well as 3 children with a bilateral lambdoid synostosis were included. RESULTS: Typical radiological characteristics in craniosynostosis exist. These features as well as its frequency in craniosynostosis in plain skull radiographs are presented. In all cases, these typical features enabled a correct diagnosis, which was confirmed by intraoperative findings. CONCLUSION: The frequency of the appearance of typical features is listed and may serve as a "mental internal check list" in the radiological approach to craniosynostosis. The study points out the value of plain skull X-rays as it enabled proper diagnosis in all investigated 127 cases.

Intraoperative 3-D imaging improves sentinel lymph node biopsy in oral cancer.

PURPOSE: The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer. METHODS: Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used. RESULTS: All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98%), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22% of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100%). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients. CONCLUSION: FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer.

3D stereophotogrammetric analysis of operative effects after broad median craniectomy in premature sagittal craniosynostosis.

INTRODUCTION: There is ongoing discussion on the diagnostic methods, the need of surgical treatment, and the surgical strategies for premature craniosynostosis. MATERIALS AND METHODS: This study examined the operative procedure of a standardized broad median craniectomy, active tilting of the forehead, and bitemporal greenstick fracturing in children with premature sagittal craniosynostosis. To objectively analyze the direct surgical results, we used a 3D stereophotogrammetry scanner, as previously described. RESULTS: A 3D analysis showed a significant increase in the width, cranial index (CI), head and coronal circumferences, intracranial volume, and cranial base width after surgery. Head length was the only parameter that demonstrated a significant decrease postoperatively. Asymmetry and the 30° diagonal difference showed no significant changes. CONCLUSION: 3D stereophotogrammetry is a reliable and valuable tool with no side effects. It demonstrated that the extended surgical procedure achieves good postoperative results with a reduced length and increased width and, therefore, an improved CI. Additionally, the total intracranial volume was significantly increased after surgery.

Successful microvascular surgery in patients with thrombophilia in head and neck surgery: a case series.

BACKGROUND: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss-which is most often caused by thrombosis-can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. CASE PRESENTATION: We present three exemplary male Caucasian patients aged 53-57 years with free flap loss owing to an underlying, hidden thrombophilia. CONCLUSION: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.

Comparison of Patient-Specific Condylar Positioning Devices and Manual Methods in Orthognathic Surgery: A Prospective Randomized Trial.

BACKGROUND: This study investigated whether patient-specific condylar positioning devices (CPDs) are beneficial compared to the conventional manual positioning of the condyles. METHODS: In this prospective, randomized trial, patients undergoing orthognathic surgery with a bilateral sagittal split osteotomy of the mandible were included. The ascending ramus was positioned with computer-aided designed and computer-aided manufactured (CAD/CAM) patient-specific devices in the CPD group and manually in the control group. Postoperatively, cone-beam computed tomography (CBCT) was performed to align the virtually planned position with the postoperative result. RESULTS: Thirty patients were enrolled in the study, with 14 randomized to the CPD group and 16 to the control group. In the CPD group, the ascending ramus differed in the postoperative CBCT scan from the virtually planned position by 0.8 mm in the left/right, 0.8 mm in the front/back, and 1.3 mm in the cranial/caudal direction. The corresponding control-group values were 1.1 mm, 1.3 mm, and 1.6 mm. CPD and controls differed significantly for the left/right movement of the rami (p = 0.04) but not for the other directions or rotations (p > 0.05). CONCLUSIONS: The results demonstrate that both methods are accurate, and postoperative results matched the virtually planned position precisely. It can be assumed that the described CPDs are beneficial when a condylar position different from the preoperative is desired.

Biological and Mechanical Performance of Dual-Setting Brushite-Silica Gel Cements.

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.