Search Results (9,093)

Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed. Full article

Diabetic foot ulceration is one of the most common complications in patients treated for diabetes mellitus. The presented pilot study describes the successful treatment of diabetic ulceration of the heel with ongoing osteomyelitis in a 39-year-old patient after using a combination of modified chitosan-based biomaterial in combination with autologous mesenchymal stem cells isolated from bone marrow and dermal fibroblasts. The isolated population of bone marrow mesenchymal stem cells fulfilled all of the attributes given by the International Society for Stem Cell Research, such as fibroblast-like morphology, the high expression of positive surface markers (CD29: 99.1 ± 0.4%; CD44: 99.8 ± 0.2% and CD90: 98.0 ± 0.6%) and the ability to undergo multilineage differentiation. Likewise, the population of dermal fibroblasts showed high positivity for the widely accepted markers collagen I, collagen III and vimentin, which was confirmed by immunocytochemical staining. Moreover, we were able to describe newly formed blood vessels shown by angio CT and almost complete closure of the skin defect after 8 months of the treatment. Full article

Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core–shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin–chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration. Full article

Background: Until now, limited clinical significance had been reported for disseminated tumor cells (DTCs) in gynecologic malignancies. DTCs were previously reported not to be associated with established risk factors, L1CAM immunoreactivity, and outcome in endometrial carcinoma (EC). This study’s primary objective was to investigate potential correlations of DTCs in the bone marrow (BM) of EC patients with disease-related survival, and a secondary objective was to evaluate associations between molecular classification of EC and DTCs. Methods: Patients treated for primary EC at Tuebingen University women’s hospital between 2003 and 2016 were identified. A total of 402 patients with a complete set of BM cytology, molecular, and clinical data were evaluable. Results: DTC occurrence was distributed equally among all four molecular groups (p = 0.651). DTC positivity was associated with a less favorable disease-free survival (HR: 1.86, 95% CI: 1.03–3.36, p = 0.036) and progression-free survival (HR: 1.86, 95% CI: 1.01–3.44, p = 0.045). Presence of DTCs was associated with a higher frequency of distant disease recurrence (p = 0.017). Conclusions: In line with our previous findings, tumor cell dissemination is not associated with molecular features in our large cohort of primary EC patients. Since DTCs seem to be associated with survival and location of disease recurrence, further studies are needed to decisively define their role in EC survival. Full article

In bone-milling surgical procedures, the intense friction between the tool and bone material often results in high cutting temperatures, leading to the thermal necrosis of bone cells. This paper aims to investigate the effect of micro-texture on the tribological properties of YG8 cemented carbide in contact with bone. The main objective is to guide the design of tool surface microstructures to reduce frictional heat generation. To minimize experimental consumables and save time, numerical simulations are first conducted to determine the optimal machining depth for the texture. Subsequently, micro-textures with different shapes and pitches are prepared on the surface of YG8 cemented carbide. These textured samples are paired with bovine cortical bone pins featuring various bone unit arrangements, and friction and wear tests are conducted under physiological saline lubrication. The experimental results indicate that the appropriate shape and pitch of the micro-texture can minimize the coefficient of friction. The parallel arrangement of bone units exhibits a lower coefficient of friction compared to the vertical arrangement. This study holds significant implications for the design and fabrication of future micro-texture milling cutters. Full article

Bone tissue engineering (BTE) is an important field of research, essential in order to heal bone defects or replace impaired tissues and organs. As one of the most used additive manufacturing processes, 3D printing can produce biostructures in the field of tissue engineering for bones, orthopaedic tissues, and organs. Scaffold manufacturing techniques and suitable materials with final structural, mechanical properties, and the biological response of the implanted biomaterials are an essential part of BTE. In fact, the scaffold is an essential component for tissue engineering where cells can attach, proliferate, and differentiate to develop functional tissue. Fused deposition modelling (FDM) is commonly employed in the 3D printing of tissue-engineering scaffolds. Scaffolds must have a good architecture, considering the porosity, permeability, degradation, and healing capabilities. In fact, the architecture of a scaffold is crucial, influencing not only the physical and mechanical properties but also the cellular behaviours of mesenchymal stem cells. Cells placed on/or within the scaffolds is a standard approach in tissue engineering. For bio-scaffolds, materials that are biocompatible and biodegradable, and can support cell growth are the ones chosen. These include polymers like polylactic acid (PLA), polycaprolactone (PCL), and certain bioglass or composite materials. This work comprehensively integrates aspects related to the optimisation of biocompatible and biodegradable composites with the low cost, simple, and stable FDM technology to successfully prepare the best designed composite porous bone-healing scaffolds. FDM can be used to produce low-cost bone scaffolds, with a suitable porosity and permeability. Full article

Nano-hydroxyapatite (nHA) demonstrates favorable biological activity, cell adhesion, cell proliferation, and osteoconductivity, making it highly valuable in biomedicine. It is extensively used as a bone substitute and in bone transplantation within the dental and orthopedic fields. This study employed oyster shells as a calcium source to synthesize nHA at 150 °C with various hydrothermal reaction durations (10 min, 1 h, 6 h, and 12 h). As a control, HA synthesized via a wet precipitation method for 1 h at room temperature was utilized. Subsequent material analyses, including XRD, FE-SEM, FTIR, and ICP-MS, were conducted, followed by comprehensive evaluations of the bioactivity, cell attachment, cell proliferation, and sintering properties of the synthesized nHA. The results indicated that nHA synthesized through the hydrothermal reaction produced nanoscale crystals, with the aspect ratio of nHA particles increasing with the duration of hydrothermal treatment. Notably, rod-like nHA particles became prominent with hydrothermal durations exceeding 6 h. nHA particles derived from oyster shells contained carbonate and trace elements (Na, Mg, K, and Sr), similar to constituents found in human hard tissue such as bone and teeth. The immersion of nHA synthesized at 150 °C for 1 h (HT2) in simulated body fluid (SBF) for 28 d led to the formation of a bone-like apatite layer on the surface, indicating the excellent bioactivity of the synthesized nHA. The cell culture results revealed superior cell attachment and proliferation for nHA (HT2). Following the sequential formation and sintering at 1200 °C for 4 h, HT2 ceramics exhibited enhanced microhardness (5.65 GPa) and fracture toughness (1.23 MPa·m^0.5), surpassing those of human tooth enamel. Full article

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. In addition to improvements in bone delivery, potential regulation of bone development mechanisms involving receptor-regulated pathways has also been utilized. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems. Full article

3D-printing technology has revolutionized spinal implant manufacturing, particularly in developing personalized and custom-fit titanium interbody fusion cages. These cages are pivotal in supporting inter-vertebral stability, promoting bone growth, and restoring spinal alignment. This article reviews the latest advancements in 3D-printed titanium interbody fusion cages, emphasizing their relevance in modern personalized surgical spine care protocols applied to common clinical scenarios. Furthermore, the authors review the various printing and post-printing processing technologies and discuss how engineering and design are deployed to tailor each type of implant to its patient-specific clinical application, highlighting how anatomical and biomechanical considerations impact their development and manufacturing processes to achieve optimum osteoinductive and osteoconductive properties. The article further examines the benefits of 3D printing, such as customizable geometry and porosity, that enhance osteointegration and mechanical compatibility, offering a leap forward in patient-specific solutions. The comparative analysis provided by the authors underscores the unique challenges and solutions in designing cervical, and lumbar spine implants, including load-bearing requirements and bioactivity with surrounding bony tissue to promote cell attachment. Additionally, the authors discuss the clinical outcomes associated with these implants, including the implications of improvements in surgical precision on patient outcomes. Lastly, they address strategies to overcome implementation challenges in healthcare facilities, which often resist new technology acquisitions due to perceived cost overruns and preconceived notions that hinder potential savings by providing customized surgical implants with the potential for lower complication and revision rates. This comprehensive review aims to provide insights into how modern 3D-printed titanium interbody fusion cages are made, explain quality standards, and how they may impact personalized surgical spine care. Full article

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in the liver and bone marrow, indicative of CAEBV. The liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores the diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management. Full article

The interaction between oral bacteria and dental implant surfaces is a critical factor in the success and longevity of dental implants. With advancements in additive manufacturing technologies, selective laser melting (SLM) has emerged as a prominent method for producing titanium implants with highly controlled microstructures and porosities. These 3D printed titanium surfaces offer significant benefits, such as enhanced osseointegration and improved mechanical properties. However, the same surface features that promote bone cell attachment and proliferation may also provide favorable conditions for bacterial adhesion and biofilm formation. Understanding the dynamics of these interactions is essential for developing implant surfaces that can effectively resist bacterial colonization while promoting tissue integration. This narrative review explores the complex interplay between oral bacteria and SLM-produced titanium porous surfaces, examining current research findings and potential strategies for optimizing implant design to mitigate the risks of infection and ensure successful clinical outcomes. Full article

Background: Disseminated tumor cells (DTCs) are thought to be the initiators of tumor recurrence and metastasis. However, based on the current imaging examination methods, early detection of DTCs is extremely difficult due to their small number and dormant state. Methods: We used the SE-iFISH approach to detect bone marrow DTCs (mDTCs) in patients with breast or prostate cancer, and compared it with various imaging examination methods to explore its role in predicting metastasis and prognosis. Results: Fifteen patients were enrolled in this study. Among them, 11 patients showed imaging-confirmed bone metastases in different sites of the body, of which seven patients had iliac mDTCs and signs of iliac bone metastases on imaging. For the remaining four patients, imaging confirmed that the bone metastatic foci were far from the ilium, but in one patient, mDTCs were detected in the ilium. Interestedly, iliac mDTCs were also detected in two out of four patients who had no sign of bone metastases on imaging. Furthermore, the epithelial marker, CK18, was ubiquitously expressed in mDTCs, but its expression was very low in peripheral circulating tumor cells (pCTCs). The Kaplan–Meier plot suggested that CK18+ mDTCs ≥ 5 was related to poor overall survival (OS) compared with that of CK18+ mDTCs < 5 in breast cancer patients (median OS: 22.1 vs. 46.9 months; log-rank, p = 0.035). Conclusions: SE-iFISH examination for mDTCs is more sensitive than the conventional methods used for detecting bone metastases. mDTC detection facilitated the early finding of tumor cells in the bone marrow and ≥5 CK18+ mDTCs was associated with a poor prognosis in breast cancer patients. Full article

Fermented foods and ingredients, including furmenties derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here, we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate, using in vitro assays, that these fermentates can differentially modulate cytokine secretion via bone-marrow-derived dendritic cells (BMDCs) when activated with either the viral ligand loxoribine or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27, and IL-10 and decrease IL-1β in primary bone-marrow-derived dendritic cells (BMDCs) stimulated with a viral ligand. In contrast, exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly, SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrate that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as ulcerative colitis (UC), and Crohn’s disease (CD). Full article

Purpose: To evaluate the prediction of vertebral fractures in plasma cell dyscrasias using dual-layer CT (DLCT) with quantitative assessment of conventional CT image data (CI), calcium suppressed image data (CaSupp), and calculation of virtual calcium-only (VCa) image data. Material and Methods: Patients (n = 81) with the diagnosis of a plasma cell dyscrasia and whole-body DLCT at the time of diagnosis and follow-up were retrospectively enrolled. CI, CaSupp25, and CaSupp100 were quantitatively analyzed using regions of interest in the lumbar vertebral bodies and fractured vertebral bodies on baseline or follow-up imaging. VCa were calculated by subtraction (CaSupp100-CaSupp25), delineating bone only. Logistic regression analyses were performed to assess the possibility of imminent spine fractures. Results: In 24 patients, new vertebral fractures were observed in the follow-up imaging. The possibility of new vertebral fractures was significant for baseline assessment of CT numbers in CI, CaSupp25, and VCa (p = 0.01, respectively), with a higher risk for new fractures in the case of lower CT numbers in CI (Odds ratio = [0.969; 0.994]) and VCa (Odds ratio = [0.978; 0.995]) and in the case of higher CT numbers in CaSupp 25 (Odds ratio 1.015 [1.006; 1.026]). Direct model comparisons implied that CT numbers in CaSupp 25 and VCa might show better fracture prediction than those in CI (R² = 0.18 both vs. 0.15; AICc = 91.95, 91.79 vs. 93.62), suggesting cut-off values for CI at 103 HU (sensitivity: 54.2%; specificity: 82.5; AUC: 0.69), for VCa at 129 HU (sensitivity: 41.7%; specificity: 94.7; AUC: 0.72). Conclusions: Quantitative assessment with CaSupp and calculation of VCa is feasible to predict the vertebral fracture risk in MM patients. DLCT may prove useful in detecting imminent fractures. Full article

Background: The diagnostic work-up of musculoskeletal tumors is a multifactorial process. During the early phase, differential diagnoses are made using basic radiological imaging. In this phase, part of the decision making is based on the patient’s age, as well as the incidence and predilection sites of different entities. Unfortunately, this information is based on older and fragmented data. In this study, we retrospectively evaluated all soft-tissue and bone tumors around the knee in children treated at our tertiary center in the last 20 years, with the aim of verifying the data used today. Methods: In this retrospective study, the databank of our tertiary center was used to give an overview of treated tumors around the knee in children. Results: We were able to include 224 children with bone and soft-tissue tumors around the knee. The cohort consisted of 184 bone tumors, of which 144 were benign and 40 malignant. The 40 soft-tissue tumors comprised 30 benign and 10 malignant masses. The most common lesions were osteochondromas (88) in the bone and tenosynovial giant-cell tumors (12) in the soft tissue. Conclusions: With this original work, we were able to verify and supplement earlier studies, as well as deepen our insight into these very rare diseases. Full article