Search Results (3,271)

Multi-material structures based on titanium alloys represent a promising approach for the fabrication of functionally graded orthopedic implants capable of combining high mechanical strength with reduced stiffness to minimize the stress-shielding effect. In the present work, multi-material Ti15Ta/Ti6Al4V specimens were fabricated by laser powder bed fusion (L-PBF) for the first time, and the processing parameters of the transition zone were systematically optimized. Three regimes were investigated: baseline (93 J/mm³), double scanning (186 J/mm³), and reduced speed (116 J/mm³). The microstructure and elemental distribution were examined by SEM and EDS; mechanical properties were evaluated through tensile testing and microhardness measurements; biocompatibility was assessed using osteoblasts and gingival fibroblasts. The double scanning regime provided the highest density of the transition zone (99.49%). Tensile failure of the specimens occurred in the Ti15Ta region, confirming the quality of the metallurgical bond. The ultimate tensile strength ranged from 534 to 543 MPa with an elongation at break of 15.7–16.4%. Heat treatment at 875 °C led to the formation of an equilibrium lamellar microstructure and smoothing of the interface. Cell viability on both alloys exceeded 88% as confirmed by flow cytometry and remained above the 70% non-cytotoxicity threshold defined by ISO 10993-5. The obtained results demonstrate the technological feasibility of fabricating multi-material Ti15Ta/Ti6Al4V structures and achieving high-quality metallurgical bonding, which constitutes a necessary first step toward the development of functionally graded orthopedic implants. Full article

Magnolia kobus (M. kobus) has long been used to treat nasal congestion, allergic rhinitis, and sinusitis. In the current study, we demonstrate the effects and underlying mechanisms of M. kobus flower water extract (ME) and ME-derived constituent magnolin on in vitro osteoblastogenic and anti-osteoclastogenic responses. Treatment with ME or magnolin markedly enhanced the osteoblast differentiation and mineralization in MC3T3-E1 pre-osteoblasts. This osteoblastogenic activity of ME or magnolin was closely associated with upregulation of osteoblast-specific molecules, including RUNX2, DLX5, OSX, alkaline phosphatase, collagen type I, and osteopontin, as well as the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Concurrently, magnolin inhibited osteoclast differentiation through inactivating MAPK pathways and downregulating NFATc1, c-Fos, tartrate-resistant acid phosphatase, and cathepsin K in RANKL-treated RAW264.7 cells. These observations suggest that ME and magnolin have pharmacological potential for the treatment and prevention of metabolic bone disorders, including osteoporosis. Full article

In the present study, vertebral bone tissues derived from Chongming crucian carp (Carassius carassius), a dominant species during the summer and autumn seasons on Chongming Island in the lower Yangtze River, were used to establish and characterize a Carassius carassius osteoblast cell line (COBC). The established COBCs were assessed using chromosome analysis, osteocalcin enzyme-linked immunosorbent assay (ELISA), and osteogenesis-related gene expression analysis. Additionally, cellular responses to environmental stress were assessed. The results showed that COBC exhibited optimal proliferation in L-15 medium supplemented with 20% fetal bovine serum at 28 °C. The histochemical staining assay results were all positive, thereby confirming that the isolated cells display typical osteoblast characteristics. Quantitative PCR analysis revealed that osteogenic marker genes, including runx2a and runx2b, were expressed at significantly higher levels in COBCs than in fish tissues. Under hypoxic stress, COBCs exhibited morphological changes, an increase in cell death, significant alterations in gene expression, and variations in antioxidant enzyme activity. These responses facilitate adaptation to hypoxic stress. This study established the first osteoblast cell line of the Chongming crucian carp and characterized its biological properties and response to hypoxic stress. These findings offer a valuable in vitro cell model and technical support for research on fish bone tissue biology and the assessment of environmental stress effects. Full article

Background: Tantalum in cytotoxicity tests showed no toxicity effect, as well as promoting bone regeneration through the differentiation, proliferation, mineralisation and adhesion of osteoblasts in in vitro and in vivo studies. This study aims to determine and compare the chemical composition, roughness and wettability of non-coated commercially pure titanium (CpTi) disc surfaces with CpTi discs that have been coated with tantalum oxynitride film (TaON) via a modified plasma sputtering coating technique. Methods: Two groups were tested that included the TaON-coated CpTi discs and non-coated CpTi discs. A modified reactive plasma sputtering apparatus was used for coating the CpTi discs with TaON at different time durations, i.e., 4, 6, and 8 h. The surface properties of the coated and non-coated discs were studied using X-ray diffraction (XRD) analysis, energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), and contact angle measurement. Results and Conclusions: The results showed that 8 h was the best coating duration. The XRD analysis showed the presence of a new peak in the case of the TaON-coated CpTi disc that was absent in the non-coated CpTi disc. Furthermore, the SEM analysis revealed that the TaON-coated CpTi disc showed a better distribution of surface roughness compared to the non-coated disc. The non-coated CpTi discs showed lower wettability compared to the TaON-coated CpTi discs. The result shows the importance of a TaON coat in changing the surface properties of CpTi which will be used in dental implants; this result will enhance the idea of surface treatment and its relationship with the enhancement and acceleration of bone formation around dental implants in future. The novelty of the newly modified reactive plasma sputtering technique used in this study as a coating technique for CpTi discs lies in the promising tantalum oxynitride, as Ta had no toxicity effect in cytotoxicity tests and promoted adhesion, proliferation, differentiation, the mineralisation of osteoblasts and bone regeneration in vitro and in vivo. The mean target of the work is to enhance the osseointegration of CPTi dental implants with different surface coatings including Ta oxide, nitride and oxynitride. The results of the first two coatings are already published, and the third coating technique is investigated in this study. Full article

This narrative review summarizes current evidence on the molecular and cellular effects of low-dose methotrexate (LD-MTX) on bone tissue. In addition, it critically examines the limited and heterogeneous data on LD-MTX-associated osteopathy, a rare and incompletely understood condition that may be underrecognized in clinical practice. Finally, the review highlights key knowledge gaps and outlines future research directions aimed at improving diagnosis, management, and prevention. In total, 451 relevant articles were retrieved, and 71 studies were included in our review. Methotrexate (MTX) has been shown to prevent bone loss associated with inflammatory rheumatic diseases, primarily through its anti-inflammatory properties. However, current evidence highlights a variety of negative effects on bone associated with LD-MTX therapy, including osteoblast dysfunction, increased osteoclastogenesis, and endothelial damage. Collectively, these effects may result in deterioration of microarchitecture, impaired bone healing and insufficiency fractures. Despite the long and successful use of MTX in rheumatology, our knowledge of its effects on bone and awareness of LD-MTX osteopathy remain limited, potentially leading to delayed or missed diagnoses. Recent clinical studies highlight the potential underestimation of this condition and emphasize the need for further research to establish clear diagnostic criteria and treatment guidelines, as well as to achieve a more comprehensive understanding of the complex pathophysiology underlying LD-MTX osteopathy. Full article

Fracture healing is a multistage regenerative process requiring the coordinated regulation of inflammation, osteogenesis, and bone remodeling, yet pharmacological agents that effectively modulate these processes remain limited. Adenophorae Radix (AR), a traditional medicinal herb used for tissue repair, has not been mechanistically investigated in skeletal regeneration. In this study, a mouse femoral fracture model was employed to evaluate the effects of short-term (7 days) and long-term (5 weeks) oral administration of AR. Bone regeneration was assessed using micro-computed tomography, histological staining, and quantitative real-time polymerase chain reaction. Network pharmacology and molecular docking were applied to predict bioactive AR constituents and their target pathways, followed by in vivo validation. Short-term AR treatment significantly upregulated osteogenic markers, including RUNX2 and osteocalcin, in the bone marrow, indicating early activation of osteoblast differentiation. Long-term administration enhanced bone mineral density, trabecular organization, and callus maturation. Network pharmacology analysis identified cycloartenol acetate, β-sitosterol, and mandenol as major active compounds targeting osteogenesis- and osteoclast-related pathways, converging on HIF1A, PTGS2, and PPARG. Molecular docking demonstrated strong binding affinities between these compounds and their predicted targets, which was supported by increased expression of HIF1A, PTGS2, and PPARG in AR-treated femora. Collectively, these findings suggest that AR promotes fracture healing by regulating osteogenic differentiation and bone remodeling through multi-target transcriptional networks. Full article

Photobiomodulation (PBM) has shown promising potential to enhance bone regeneration; however, its optimal delivery parameters and interactions with osteoconductive scaffolds remain insufficiently defined. This preclinical study is the first to incorporate a pilot dosimetry evaluation to standardize 980-nm PBM delivery and ensure that effective irradiance reached the target surface of critical-size calvarial defects in mice. The primary aim was to evaluate the effectiveness of this novel 980-nm PBM protocol delivered using either flat-top (FT) or standard Gaussian (ST) handpieces in enhancing bone regeneration in critical-size defects (CSDs), both with and without Bio-Oss^® grafting. A total of 120 adult mice were allocated into twelve experimental groups (n = 10 per group): untreated (control), Bio-Oss^® alone, PBM alone, and PBM combined with Bio-Oss^®, using either FT or ST handpieces, and evaluated at 30 and 60 days. Animals received 980 nm irradiation at 0.6 W (nominal power output–set on laser interface) in continuous-wave mode for 60 s, three times per week, for two consecutive weeks. Pilot dosimetry included power meter measurements to determine the therapeutic power reaching the defect surface area and temperature monitoring to ensure safe energy delivery. The dosimetry study demonstrated that, after accounting for the optical properties of mouse shaved skin and the Bio-Oss^® graft covered with Bio-Gide^® membrane, the effective irradiance reaching the base of the defect surface area was 1.131 W/cm² for the FT handpiece and 0.413 W/cm² for the ST handpiece. This dose was sufficient to induce significant regenerative effects. Histological, Masson’s trichrome, and immunohistochemical analyses for Runx2, OCN, GLI1, CD34, and CTSK were performed to characterize early and late osteogenic events. The combination of PBM and Bio-Oss^® significantly accelerated bone regeneration compared with PBM alone, with the FT handpiece producing the most uniform and advanced osteogenesis. PBM enhanced progenitor activation, osteoblast differentiation, angiogenesis, matrix deposition, and late-stage remodeling, demonstrating a synergistic effect with the scaffold, whereas Bio-Oss^® alone or defect alone showed limited early regenerative potential. These findings highlight the effectiveness of this novel standardized PBM dosimetry and uniform beam profile (FT), supporting their use as a foundation for future randomized controlled trials in craniofacial bone repair. Full article

Developing novel anabolic agents for bone regeneration remains a clinical priority. Polydeoxyribonucleotide (PDRN) exhibits tissue-regenerative properties, but its direct cellular effects on bone remodeling remain unclear. This in vitro study investigated PDRN’s effects on osteoblast (MC3T3-E1) and osteoclast (primary bone marrow-derived macrophages) differentiation. We evaluated metabolic activity, gene/protein expression, and specific differentiation markers using MTS, qRT-PCR, Western blotting, and functional assays (ALP, Alizarin Red S, TRAP, pit formation). In osteoblasts, PDRN dose-dependently modulated metabolic activity while upregulating the early transcription factor Runx2. PDRN significantly enhanced osteoblast differentiation, evidenced by increased ALP activity, elevated mineralized matrix deposition, and robust upregulation of osteocalcin and Runx2. Conversely, PDRN exhibited no direct effect on osteoclast precursor metabolic activity, differentiation, or resorptive function. These findings support a working hypothesis in which PDRN selectively promotes osteoblast differentiation without directly affecting osteoclastogenesis. While further pharmacological investigations are required to definitively elucidate the specific purinergic receptor mechanisms, our results highlight PDRN as a promising candidate anabolic agent for bone regeneration. Full article

Background/Objectives: Bone metastases are a common complication of breast cancer. In our previous study, we reported that extracellular vesicles released by osteotropic human (MDA-MB-231) and murine (4T1) breast cancer cells disrupt bone homeostasis by enhancing osteoclast differentiation and impairing osteoblast function. Based on these findings, we investigated whether microRNAs contained within tumour-derived EVs could mediate these bone-altering effects. Methods: MDA-MB-231- and 4T1-EVs were tagged with the RNA-specific fluorophore SYTORNA and employed to treat mouse primary bone marrow macrophages (BMMs) and osteoblasts (OBs). We also performed RNAseq on MDA-MB-231- and 4T1-EVs to assess their miRNAs content. Finally, we evaluated the effect of selected miRNA-mimics on OBs, BMMs and HUVEC cells. Results: Fluorescence microscopy demonstrated EV-RNAs shuttling to recipient cells, while RNA sequencing on MDA-MB-231- and 4T1-EVs revealed that, of the top 20 expressed miRNAs, 10 were common. Among them, we first focused on the following four: miR-26a-5p, miR-24-3p, miR-29a-3p, and miR-29b-3p, which were linked to bone biology. We confirmed their presence in MDA-MB-231-/4T1-EVs by qPCR. Then, we evaluated their EV-mediated shuttling to BMMs and OBs using affinity tags. Among all the conditions tested, miR-29a and miR-29b were the best-shuttled miRNAs, with efficiency between 50–100% in both OBs and BMMs, both for MDA-MB-231- and 4T1-EVs. Finally, to test whether miR-29a and miR-29b could have a functional role in bone cells, OBs were transfected with miR-29a and 29b-mimics, discovering that this treatment reduced collagen1α1 and 1α2 mRNA as well as the OBs’ mineralisation ability, while the same miRNA mimics were found to have no effect on osteoclastogenesis or on in vitro angiogenesis. Conclusions: MDA-MB-231- and 4T1-EVs shuttle miRNAs to bone cells, which likely contributes to OBs’ activity impairment. Full article

Regenerative medicine based on Mg alloy implants is considered a modern approach to address bone defects. It represents a promising alternative to traditional grafting strategies (auto-, allo-, and xenografts) by potentially mitigating complications such as donor-site morbidity and limited supply, which are discussed in this paper. In line with this global topic, attention is devoted to an innovative manufacturing route for Mg-Nd and Mg-Zn implants for the treatment of small bone defects. First, the proposed manufacturing method is described in detail, including the materials used and the manufacturing steps, and then a comparison between the reference (cast alloys) and implant samples is performed. The mechanical properties, weight loss in simulated body fluid (SBF), surface analysis (contact angle and roughness measurements), and cytotoxicity were evaluated to determine whether the developed implants are suitable for consideration as future bone implants. The main conclusions of the study were that both Mg-based implants exhibited mechanical properties (compressive strength and Young’s modulus) with values very close to those of the human bone, reduced mass loss (a fact that is in a direct relationship with an increase in corrosion resistance due to MgF₂ conversion coating, which is a secondary result of the proposed manufacturing route), and finally, a good biocompatibility sustained by cell culture and cytotoxicity assessment, as well as by apoptosis and necrosis analysis on a human patella-derived osteoblastic cell line. Full article

Prenatal exposure to aflatoxin B₁ (AFB₁) poses a significant risk to fetal development and is associated with reduced birth weight in humans. Experimental studies consistently show that AFB₁ induces fetal abnormalities, with skeletal malformations and ossification defects being the most common. However, the specific impact of AFB₁ on fetal osteogenesis remains unclear. Given this knowledge gap, this study aimed to review the existing literature concerning the pathogenesis of AFB₁ and its potential influence on bone development. The primary mechanisms implicated in AFB₁’s impact on bone include dysfunction in vitamin D and calcium metabolism, alterations in parathyroid hormone production and function, induction of inflammatory responses, and oxidative stress. Collectively, these mechanisms have the potential to impair osteoblast and osteoclast function and, consequently, compromise ossification. Based on these findings, studies should explore and elucidate the effects of AFB₁. Elucidating these mechanisms is crucial for mitigating the deleterious impacts of AFB₁ on fetal skeletal development. Full article

Background: Bone remodeling depends on the dynamic balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Follistatin-like 1 (FSTL1) has been reported as an osteoclast-secreted protein that inhibits osteoclast differentiation, but its direct effects on osteoblast differentiation remain unclear. This study aimed to determine whether FSTL1 regulates osteoblast differentiation and mesenchymal stem cell migration and characterizes its role in osteoclast-osteoblast cellular cross-talk under in vitro conditions. Methods: Bone marrow-derived macrophages (BMMs) and stromal cells (BMSCs) from mice were used to induce osteoclast and osteoblast differentiation, respectively. Chemotaxis was assessed by Transwell migration, and osteoblast differentiation was evaluated in BMSC and MC3T3-E1 cells using staining, qRT-PCR, Western blotting, and proliferation assays. Results: FSTL1 significantly suppressed osteoclast differentiation and resorptive activity, confirmed by TRAP staining and pit assay, respectively. Expression of osteoclast markers such as NFATc1, TRAP, and DC-STAMP was reduced under FSTL1 treatment. In BMSCs, FSTL1 did not affect proliferation but significantly enhanced chemotaxis. Moreover, FSTL1 promoted osteogenic differentiation and mineralization, as demonstrated by increased ALP activity and Alizarin Red S staining. In MC3T3-E1 pre-osteoblasts, FSTL1 increased cell proliferation and mineralization by MTS and Alizarin Red staining. Key osteogenic markers, including Runx2 and osteocalcin, were also upregulated. Conclusions: Osteoclast-derived FSTL1 significantly suppresses osteoclastogenesis and promotes mesenchymal cell chemotaxis and osteogenic differentiation, indicating a role in regulating osteoclast–osteoblast cellular interactions in vitro. Targeting FSTL1 signaling may represent a promising therapeutic strategy for osteoporosis and other disorders of impaired bone remodeling. Full article

Osteal macrophages (“osteomacs”) are resident bone macrophages that support osteoblast differentiation and bone formation. Despite their importance in bone homeostasis, their function in human bone metabolism and osteoporosis remains poorly understood, largely due to the lack of a standardized isolation protocol. Here, we present a protocol for isolating primary human osteomacs from femoral head specimens obtained during arthroplasty. After the removal of bone marrow to minimize contamination with marrow-derived macrophages, bone fragments were enzymatically digested and osteomacs were isolated using CD14-based MACS^® or CD14/CD45/ALP-based FACS. Immunofluorescence confirmed macrophage identity and revealed expression of markers associated with both M1-like and M2-like activation states. Isolated cells displayed heterogeneous morphology and could be maintained in culture. This protocol enables reproducible isolation of human osteomacs and provides a foundation for translational studies investigating osteoimmune interactions in bone disease and osteoporosis. Full article

From a mechanical stimulation perspective, this study aims to explore the mechanisms by which dance training affects bone metabolism and to clarify its potential as a preventive and therapeutic measure for osteoporosis (OP). A comprehensive search was conducted on the PubMed, Web of Science, and China National Knowledge Infrastructure databases, utilizing search terms related to dance, mechanical stimulation, and OP. The present study incorporated a wide range of research methodologies, including randomized controlled trials, observational studies, systematic reviews, and narrative reviews, with the overarching objective of encompassing all pertinent concepts within the purview of our investigation. The synthesis and description of the search results were conducted through a narrative approach. A preliminary investigation of extant literature suggests that studies that comprehensively delineate the mechanism of action between dance and OP are few and far between. However, a thorough review of the extant literature indicates that dance training can enhance bone density and promote skeletal health by influencing mechanical characteristics. Concurrently, dance can function as a mechanical stimulus, thereby regulating bone metabolism by activating relevant cellular signaling pathways, thus contributing to the reduction of bone loss. Dance training, as a form of mechanical stimulation, has the potential to play a crucial role in the prevention and treatment of OP. However, the precise nature of the dance styles, the training intensities and frequencies remains unclear. It is recommended that future research endeavors concentrate on the comprehensive integration of these measures, with the objective of addressing the existing knowledge gaps. This approach is expected to provide a more robust evidence base for the utilization of dance-based strategies in the prevention and management of OP. Full article

Background and Objectives: Soft tissue regeneration in oral surgery has undergone remarkable progress in the last decade, supported by the development of innovative laser technologies, advanced biomaterials, platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), and three-dimensional (3D) printing. Lasers are increasingly used not only for incision and coagulation but also for photobiomodulation, promoting cellular proliferation, angiogenesis, and tissue healing. The purpose of this review is to analyze the current advances in soft tissue regeneration, with a particular focus on the clinical use of lasers and their integration with other regenerative strategies. In parallel, hard tissue regeneration has evolved through the synergistic use of bioactive scaffolds, recombinant human growth factors (rhBMP-2, rhPDGF-BB), MSCs, and 3D-printed constructs. These innovations have enhanced alveolar bone regeneration, implant osseointegration, and periodontal tissue repair, offering predictable clinical outcomes. Materials and Methods: A review of the literature published between 2015 and 2025 was conducted through PubMed, Scopus, Web of Science, Embase, and Google Scholar. Clinical and preclinical studies on the use of CO₂, Nd:YAG, Er:YAG, diode, and 445 nm lasers, biomaterials, PRP, MSCs, growth factors, and 3D-printed scaffolds were included. Results: Laser applications demonstrated significant benefits in epithelialization, biostimulation, and reduction in postoperative discomfort in soft tissues. For hard tissues, the combined use of MSCs, bioactive scaffolds, and growth factors promoted osteogenic differentiation, bone volume preservation, and improved mechanical stability. Photobiomodulation enhanced osteoblastic activity and accelerated bone remodeling, while 3D-printed scaffolds provided personalized architecture for optimal integration. Conclusions: Regenerative approaches integrating lasers, biomaterials, PRP, MSCs, growth factors, and 3D printing represent safe, minimally invasive, and effective strategies for the regeneration of both soft and hard oral tissues. These multidisciplinary techniques improve healing quality, functional recovery, and esthetic outcomes, reflecting the growing trend toward precision and technology-driven regenerative oral surgery. Full article