Search Results (944)

Background: We evaluated certain factors relative to onion (Allium spp.) and onion-derived polyphenols. Methods: We searched PubMed, Scopus, and Google Scholar from 2010 to 20 October 2025 without language limits. Eligible designs comprised of in vitro, animal, and human studies assessing onion, onion extracts, or isolated onion-derived polyphenols with bone outcomes. Two reviewers independently screened, extracted, and assessed risk of bias (RoB 2 for RCTs; SYRCLE for animals). Results: We included X studies (a in vitro, b animal, and c human RCTs; N samples). In vitro limitations included the following: heterogeneous models, short human follow-up, small samples, and moderate-to-serious risk of bias in animals. Reports included improvements in bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and osteoclast/osteoblast activity. Onion extracts consistently inhibited RANKL-induced osteoclastogenesis while sparing osteoblast function. In animals, onion or quercetin/kaempferol preserved BMD and improved mineral content and (in several models) fracture healing. In one small RCT of onion juice (8 weeks), antioxidant status improved with a trend to attenuated BMD loss; a resveratrol RCT was excluded/included as a benchmark. Conclusions: Pre-clinical evidence suggests anti-resorptive and osteogenic effects of onion-derived polyphenols; human evidence is limited and characterized by low certainty. Longer RCTs are needed to define effective doses and clinical relevance. Full article

This work describes the preparation and characterization of chitosan-based biopolymer coatings containing silver, zinc, and hydroxyapatite nanoparticles deposited on the Ti13Zr13Nb alloy by the EPD method. It was intended to evaluate the influence of surface pretreatments and deposition parameters on the structural, electrochemical, and biological properties of coatings. The morphology and composition were characterized by means of SEM/EDS, AFM, XRD, and FTIR analysis. The obtained results indicated uniform continuous layers with homogeneously distributed nanoparticles and the presence of characteristic functional groups originating from chitosan and hydroxyapatite. Corrosion investigations performed in SBF solution revealed a significant enhancement in corrosion resistance for chitosan/nanoAg/nanoZn/nanoHAp coatings, reflected in a drastic decrease in corrosion current density compared with uncoated Ti13Zr13Nb alloy. The contact angle measurements confirmed their hydrophilic nature, which favors better biointegration ability. Biological tests (MTT and LDH) performed on human osteoblasts (hFOB 1.19) confirmed high biocompatibility (>85% cell viability) in the case of all coatings with the addition of hydroxyapatite, whereas in the case of coatings without HAp, cytotoxicity was observed, probably due to the uncontrolled release of metallic nanoparticles. These findings suggest that the presence of hydroxyapatite in chitosan-based coatings efficiently enhances corrosion protection and cytocompatibility, showing very good prospects for biomedical applications such as the surface modification of titanium implants. Full article

Zirconia is widely used for customized implant abutments owing to its esthetics, strength, and biocompatibility; however, the optimal surface modification for soft-tissue sealing and bone metabolic remains uncertain. This study evaluated how glass–ceramic spray deposition (GCSD), with or without handheld nonthermal plasma (HNP), alters zirconia surface physiochemistry and cellular responses. Field-emission scanning electron microscopy/energy-dispersive X-ray spectroscopy, surface roughness (Ra), wettability, and surface free energy (SFE) were measured. Human osteoblast-like cells (MG-63) and human gingival fibroblasts (HGF-1) were used to assess attachment and spreading, metabolic activity, cytotoxicity, and inflammatory response (tumor necrosis factor-α, TNF-α) (α = 0.05). GCSD produced an interlaced rod- and needle-like glass–ceramic layer, significantly increasing Ra and hydrophilicity. HNP further reduced surface contaminants, increased SFE, and enhanced wettability. The combination of GCSD and HNP yielded the greatest attachment and spreading for both cell types, without increases in cytotoxicity or TNF-α. GCSD with HNP creates a hydrophilic, micro-textured, chemically activated zirconia surface that maintains biocompatibility while promoting early attachment and bone metabolic activity, supporting its application for zirconia implant abutments. Full article

The number of endoprosthetic implants is constantly increasing. Successful osseointegration of the inserted material into the bone is essential for a prosthesis to remain in the bone as long as possible. In the clinical setting, a roughened titanium surface of implants is used as standard to enable the best possible osseointegration. Vitamin K2 and vitamin D3 play a decisive role in dynamic bone metabolism and therefore also influence osseointegration. For the first time, we carried out in vitro investigations with clinically relevant cells, primary healthy human osteoblasts (hOBs). We qualitatively compared the adhesion behaviour of hOBs on a plastic surface, a smooth, regular titanium surface structure and a roughened, irregular titanium surface structure by scanning electron microscopy and fluorescence microscopy. The osteogenic behaviour and the osteogenic differentiation capacity were quantitatively investigated by analysing the activity of alkaline phosphatase and the alizarin red S assay under the influence of vitamin K2, vitamin D3 and the combination of both vitamins. It was shown that more adhesion points formed between the cells and the titanium on the rough surface structure. In addition, a solid cell network developed more quickly on this side, with cell runners forming in three-dimensional space, which means the interactions between the cells across different cell layers. On the other hand, a structured cell network also appeared on the regular smooth surface structure, which means that the network seems to be formed and built up along a defined structure. The addition of vitamins further increased the osteogenic differentiation capacity on the rough titanium surface structure. In particular, the isolated addition of vitamin K2 showed an improved osteogenic differentiation in the long-term observation, whereas the combined addition of both vitamins promoted the initial osteogenic differentiation. Vitamin K2, therefore, plays a greater role in osseointegration than previously assumed. This opens up new possibilities for the use of vitamin K2 during and after the surgical insertion of an implant. The use of vitamin K2 should be reconsidered for clinical applications in implant care and further investigated clinically. Full article

Background: Oxidative stress and inflammation contribute to osteoporosis. Berries provide polyphenols especially anthocyanins that may modulate bone remodeling. This review is the first to synthesize evidence specifically on berries and bone health, integrating human, animal, and in vitro data under the GRADE framework. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library through 23 April 2025 for human, animal, and in vitro studies on berries or berry-derived compounds and bone outcomes. Risk of bias was assessed with RoB 2.0, ROBINS-I, SYRCLE, and an adapted ToxRTool; certainty of human evidence was appraised with GRADE. Results: Nineteen studies were included (5 human, 9 in vivo, 5 in vitro). Observational cohorts linked higher anthocyanin intake with greater BMD. Small randomized trials suggested modest benefits of blackcurrant and blueberry on whole-body BMD, bone turnover markers, and calcium retention, while results for biomarkers were mixed. Animal models generally showed attenuation of ovariectomy- or age-related bone loss, and in vitro experiments indicated inhibition of osteoclastogenesis with stimulation of osteoblast activity. By GRADE, certainty was low–moderate for BMD, low for biomarkers, and very low for fractures. Conclusions: Berry polyphenols may support skeletal health via antioxidant and anti-resorptive mechanisms, but current clinical evidence is limited by small samples, heterogeneity, and lack of fracture outcomes. Larger, longer, standardized RCTs with exposure profiling are needed before dietary recommendations can be made. Full article

Calcium phosphates, including hydroxyapatite, are widely used biomaterials in bone tissue regeneration due to their bioactivity, osteoconductivity, and similarity to the mineral phase of bone. In this study, various apatite calcium phosphate powders were synthesized using three precipitation methods, with controlled pH conditions and reagent ratios, to assess the effect of the synthesis method on their physicochemical and biological properties. Elemental composition (Ca/P ratio), FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with EDS, and particle size measurements were used to determine the structure, morphology, and stoichiometry of the obtained powders. The results indicated that the synthesis method and pH significantly affect the phase composition of the material, particle size, and Ca/P ratio, which directly influence their solubility and bioactivity. Microbiological tests, NF-κB transcription factor activation, metabolic activity, and cell compatibility of mouse L929 fibroblasts and human hFOB 1.19 osteoblasts showed good biological tolerance of the obtained powders and no cytotoxic effects. The results confirm that a properly selected synthesis method allows for the control of material properties, which is crucial for applications in bone tissue engineering. The materials show potential for use as bioactive components in bone-related biomaterials. Full article

Background and Objectives: Heterotopic ossification (HO) involves abnormal bone growth in soft tissues. Current treatments are ineffective and prone to adverse effects, suggesting the need for new HO therapies. Intramembranous bone growth is led by osteoblasts. Since osteoblastogenesis and adipogenesis are opposed and mutually controlled processes, this study aims to identify a new repurposed therapeutic tool to inhibit osteoblastogenesis through adipogenesis promotion. Methods: We performed docking experiments between peroxisome proliferator-activated receptor-γ and bone metabolism-affecting drugs, namely, thiazolidinediones (rosiglitazone, pioglitazone), indomethacin, and dexamethasone, to test tritherapy antiosteoblastogenic effect. Mouse mesenchymal stem cells (C3H10T1/2), human osteoblast-like cells (SaOS2 and primary preosteoblasts), and mouse chondrocytes (ATDC5) were differentiated in the presence of these compounds. The effects on osteoblastogenesis, adipogenesis, and endochondral ossification were analysed through marker gene expression via RT–qPCR. Additionally, primary human HO cells and a congenital HO patient were treated with the selected drug combination (P-tritherapy). Results: Tritherapy significantly and synergistically promoted the expression of an adipogenic marker (fatty acid-binding protein 4) and decreased the expression of an osteoblastogenic marker (osteopontin). In an endochondral ossification model, it reduced ossification markers (collagen-2α1) expression, and in HO cells, it increased adipogenesis markers’ expression. Clinically, P-tritherapy administration prompted bone resorption in a patient with progressive osseous heteroplasia. Conclusions: Tritherapy induced adipogenesis while inhibiting osteoblastogenesis and endochondral ossification, demonstrating its potential as a new therapeutic tool to prevent abnormal bone growth. These results were consistent with bone turnover modification observed in a congenital HO patient. This concordance underscores tritherapy potential for rapid and safe translation to prevent HO. Full article

(1) Background: Zirconia (ZrO₂) is increasingly used in dental implantology due to its biocompatibility and favorable mechanical and biological properties. While subtractive and stereolithographic additive manufacturing techniques are well established, the application of Fused Filament Fabrication (FFF) for zirconia-based dental implants remains largely unexplored. (2) Methods: Cylindrical ZrO₂ specimens were fabricated using three different manufacturing techniques: milling (MIL), Digital Light Processing (DLP), and FFF. Surface topography was analyzed via white-light interferometry. Human fetal osteoblasts (hFOBs 1.19) were cultured on the specimens to evaluate cell adhesion after 4 and 24 h, proliferation for 4 days, cell surface coverage after 4 and 24 h, and osteogenic gene expression (RUNX2, ALPL, and BGLAP) after 24 h, 48 h, 7 days, and 14 days. (3) Results: The FFF samples exhibited significantly higher surface roughness than the MIL and DLP specimens. After 24 h, enhanced cell adhesion and the highest proliferation rates were observed on FFF surfaces. At 14 days, gene expression analysis revealed elevated expression of BGLAP on FFF surfaces, suggesting advanced osteogenic differentiation compared to MIL and DLP. (4) Conclusions: The inherent surface roughness of FFF-printed zirconia appears to promote osteogenic activity without additional surface treatment. These findings suggest that FFF may constitute a viable manufacturing method for the fabrication of customized zirconia components in dental implantology, warranting further investigations, particularly regarding their mechanical performance. Full article

Dental materials are well-established, with stainless steel 316L (SS) still being a common choice for components such as pediatric crowns and abutments. However, SS has some drawbacks, particularly in terms of mechanical properties and, more importantly, aesthetics, due to its metallic gray color. In this sense, PEEK (polyetheretherketone) has emerged as a promising material for dental applications, combining good mechanical properties with improved aesthetic features. This study compared the cytocompatibility of PEEK TiO₂ composite and SS using human fetal osteoblasts (hFOB) and human gingival fibroblasts (HGF). Cytocompatibility was evaluated over 1–7 days through metabolic activity and alkaline phosphatase (ALP) assays. Additionally, bacterial adhesion was assessed using Staphylococcus aureus and Pseudomonas aeruginosa in both monoculture and co-culture. The results showed that both materials were non-cytotoxic and supported cell growth. Notably, after 7 days of culture, PEEK TiO₂ surfaces promoted approximately 7% higher ALP activity than stainless steel, demonstrating a significantly enhanced osteogenic response (p < 0.01). Moreover, at day 7, PEEK TiO₂ promoted ~25% higher metabolic activity in HGF cells compared to SS. Regarding the bacterial adhesion, it was consistently low in PEEK TiO₂ for both S. aureus and P. aeruginosa, with a marked reduction (~50%) observed for P. aeruginosa under co-culture conditions. PEEK TiO₂ demonstrated enhanced biological performance and lower bacterial adhesion compared with SS, highlighting its potential as a biocompatible and aesthetically promising option for dental applications, including pediatric crowns. Full article

Background/Objectives: Human ovarian granulosa cells (hGCs) are crucial to ovarian follicle development and function, exhibiting multipotency and the ability to differentiate into neuronal cells, chondrocytes, and osteoblasts in vitro. 3,4,5,4′-tetramethoxystilbene (DMU-212) is a methylated derivative of resveratrol, a natural polyphenol found in grapes and berries, with a wide spectrum of biological activities, including notable anticancer properties. Interestingly, DMU-212 exhibits cytotoxic effects predominantly on cancer cells while sparing non-cancerous ones, and evidence suggests that similar to resveratrol, it may also promote hGC differentiation. This study aimed to investigate the effects of the liposomal formulation of this methylated resveratrol analog—lipDMU-212—on the osteogenic differentiation ability of hGCs in a primary three-dimensional cell culture model. Methods: lipDMU-212 was formulated using the thin-film hydration method. GC spheroids’ viability was evaluated after exposure to lipDMU-212, an osteoinductive medium, or both. Osteogenic differentiation was confirmed using Alizarin Red staining and quantified by measuring Alkaline Phosphatase (ALP) activity on days 1, 7, and 15. RNA sequencing (RNA-seq) was performed to explore molecular mechanisms underlying lipDMU-212-induced differentiation. Results: lipDMU-212 promoted osteogenic differentiation of hGCs in the 3D cell culture model, as evidenced by increased mineralization and a ~4-fold increase in ALP activity compared with the control. RNA-seq revealed up-regulation of genes related to cell differentiation and cellular identity. Furthermore, JUN (+2.82, p = 0.003), LRP1 (+2.06, p = 0.05), AXIN1 (+3.02, p = 0.03), and FYN (+3.30, p = 0.01) were up-regulated, indicating modulation of the Wnt/β-catenin signaling pathway, a key regulator of osteoblast differentiation. Conclusions: The ability of GCs to differentiate into diverse tissue-specific cell types underscores their potential in regenerative medicine. This study contributes to the understanding of lipDMU-212’s role in osteogenic differentiation and highlights its potential in developing future therapies for degenerative bone diseases. Full article

The production of green nanomaterials has drawn considerable interest lately in the fields of tissue engineering and biomedicine. Thus, the environmentally friendly synthesis of ZnO and CuO nanoparticles (NPs) utilizing orange peel extract as a natural capping and reducing agent is the main focus of this study. Our comprehensive approach allows for a direct and systematic comparison of physicochemical attributes, biocompatibility, and antimicrobial activity under identical experimental circumstances, in contrast to other research that looked at individual nanoparticles under different conditions. The produced nanoparticles were characterized by techniques such as FTIR, XRD, SEM, TGA, and zeta potential assessment. MG-63 osteoblast-like cells, primary human dermal fibroblast BJ cells, and murine fibroblast L929 cells were used to evaluate biocompatibility using the MTT assay. The results showed dose-dependent cytotoxicity, especially above 25 µg/mL. Furthermore, both qualitative (growth inhibition zone diameter) and quantitative (minimum inhibitory concentration, MIC) techniques were used to assess the antimicrobial efficacy against Candida albicans and Gram-positive and Gram-negative bacteria. According to the obtained results, ZnO NPs showed broad-spectrum efficacy, whereas CuO NPs showed excellent antibacterial activity against Gram-positive bacteria (e.g., S. aureus, MIC = 0.313 μg/μL). The study highlights the potential of green-synthesized nanoparticles for utilization in biomedical applications, and it stresses the need for additional mechanistic research, including ROS measurement, to completely understand how they work. Full article

Bone remodeling relies on the coordinated activity of osteoblasts (OBs) and osteoclasts (OCs). Disruptions in OB-OC balance can lead to diseases such as periodontitis, a chronic microbial-induced inflammatory disease. To investigate how inflammation affects OB-OC interactions, we standardized an in vitro 2D indirect co-culture system using primary human OB and OC precursors from peripheral blood mononuclear cells in a transwell setup, which allows paracrine signaling and separate analysis of each cell type. When exposed to bacterial lipopolysaccharides (Aa LPS and E. coli LPS) and proinflammatory cytokines (IL-6 and TNF-α), we observed that inflammatory stimuli significantly increased OC differentiation, particularly TNF-α, while E. coli LPS specifically suppressed OB activity as observed by the expression of key markers and cellular staining. These results demonstrate that microbial and host-derived inflammatory factors can differentially modulate bone cell behavior. This approach offers a physiologically relevant and ethically advantageous alternative to animal models to screen dual-targeted bone therapies to restore perturbed metabolism. Full article

Despite the rising incidence of osteoporosis (the most common bone disorder) as life expectancy increases worldwide, the genetic and metabolic factors contributing to this multifactorial disease are still poorly understood. This study investigated the role of arginine metabolism in bone formation and its potential for preventing bone loss in postmenopausal osteoporosis. The osteogenic effects of arginine were evaluated in vitro by determining calcium mineral deposition and the expression of marker genes in the human osteoblastic cell line Saos-2. In vivo analyses were conducted in ovariectomized mice treated with arginine, focusing on femoral bone microarchitecture, marker gene expression and serum metabolite profiles. Arginine treatment enhanced calcium deposition and osteoblastic differentiation in vitro. In contrast, however, this treatment had a deleterious effect in vivo, exacerbating trabecular bone loss. These results are particularly relevant given the wide availability of arginine as a dietary supplement, and our findings underscore the necessity of verifying the safety of nutritional supplements in different populations and in the presence of disease. Full article

Cell–cell communication and extracellular matrix (ECM) organization in a bone microenvironment are essential to replicate the bone microenvironment accurately. In this study, the extracellular matrix (ECM) was emulated by incorporating M13 phages, selected through phage display for displaying engineered peptides that mimic bone matrix proteins, into human osteoblast cultures to develop a three-dimensional bone model (3D BMP-Phage). Comprehensive analysis was performed to investigate: (i) the morphological development of spheroids, assessed by optical microscopy and quantified via fractal dimension analysis using box-counting algorithms; (ii) the biochemical composition of the extracellular matrix, evaluated by Raman spectroscopy; (iii) ECM protein deposition, analyzed through immunofluorescence staining; (iv) matrix mineralization, assessed by Alizarin Red staining and alkaline phosphatase (ALP) activity assay; and (v) osteogenic gene expression, measured by quantitative RT-PCR. The findings demonstrate that the 3D BMP-Phage model, facilitated by a cocktail of bone-mimicking peptides, enhances structural integrity, ECM complexity, mineralization, and osteogenic pathways compared to the control. This novel approach replicates key aspects of the bone microenvironment, providing a valuable platform for advanced physiological and regenerative medicine research under controlled conditions. Full article

This study presents the development of a degradable and biocompatible calcium phosphate cement (CPC) co-loaded with gentamicin (1.25 wt%) and vancomycin (4.25 wt%) for the local treatment of polymicrobial bone infections. The antibiotics were incorporated—individually or in combination—into the solid phase of Graftys^® Quickset (GQS), an injectable CPC. Antibiotic loading modifies some of the intrinsic properties of the GQS cement. Porosity exceeded 53%, compressive strength reduced around 5 MPa, which is comparable to calcium sulphates cements, and the setting time, although extended, remained within the clinically acceptable threshold (<20 min), ensuring suitable handling. A burst release of both antibiotics was observed within the first 24 h, with sustained release over time and no cytotoxic effects on human osteoblasts. The dual-loaded cement exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative strains, including methicillin-resistant isolates, in both planktonic and biofilm forms. Notably, the combination of both antibiotics demonstrated superior efficacy compared to either antibiotic alone. These findings suggest that this dual-antibiotic-loaded CPC offers a promising strategy for localised treatment of complex bone infections such as osteomyelitis, where polymicrobial involvement and antibiotic resistance pose significant therapeutic challenges. Full article