Search Results (1,619)

Bone is a dynamic and multifunctional tissue that provides mechanical support, regulates mineral homeostasis, supports hematopoiesis, and relies on complex interactions among multiple cell types. The increasing incidence of bone-related diseases, such as osteoporosis, osteoarthritis, fracture non-union, and bone cancer, highlights the need for in vitro models that better reflect human bone physiology. Bone-on-a-chip technology, developed through advances in microfluidics, biomaterials, and tissue engineering, offers a promising approach to recreate key features of the bone microenvironment in vitro. By incorporating bone-mimicking materials, relevant bone cells, vascular components, fluid perfusion, and mechanical stimulation, these platforms allow more realistic investigation of bone remodeling, regeneration, disease mechanisms, and drug responses. In parallel, bone organoids and their integration with microfluidic chips have further expanded the capabilities of in vitro bone models by enabling the formation of self-organized, human-relevant bone tissues with increased cellular complexity. This review summarizes recent progress in bone-on-a-chip systems, including models for osteogenesis and bone regeneration, vascularized bone, bone marrow and hematopoietic niches, cancer bone metastasis, and mechanobiological studies. Key design principles, materials, cellular components, and applications in disease modeling, drug screening, toxicity assessment, and personalized medicine are discussed. Current challenges and future directions are also discussed to support the continued development of more physiologically relevant in vitro bone models. Full article

Endoperoxide-containing molecules based on the antimalarial drug artemisinin have demonstrated various biological properties, including modulation of calcium homeostasis. This study evaluated the toxicity and osteogenic activity of five newly developed tetraoxanes (YB1, YB9, YB11, YB17 and T2), alongside three of their non-peroxidic analogues (IC22, IC26 and IC33), in zebrafish (Danio rerio) larvae. For each compound, LC₅₀ values were first determined. Behavioural responses and morphological alterations were studied as indicators of toxicological impact. The osteogenic activity was assessed through the operculum assay, followed by the analysis of gene expression markers related to calcium homeostasis (atp2a1), oxidative stress (sod1, cat), and osteogenesis (sp7, oc2). All the compounds evaluated induced an inhibition of osteogenic activity. T2, YB11, IC33 and IC26 affected the locomotor function by decreasing swimming activity. IC26 and IC33 induced morphological toxicity, characterized by a curved trunk and alterations in larval body curvature. From all the compounds studied, YB1, YB9, YB17 and IC22 showed selective anti-osteogenic activity, without displaying significant behavioural or morphological toxicity. In conclusion, the presence of a peroxide bond in the molecular structure of the compounds increases the anti-osteogenic activity at lower concentrations. All evaluated compounds exhibited anti-osteogenic activity and can be regarded as anti-osteogenic agents. However, YB17 did not induce transcription alterations in the genes analyzed and may thus represent the most promising compound in conditions where a controlled inhibition of bone formation is desirable. Full article

Background/Objectives: Jaw osteomyelitis (OM) is a refractory purulent inflammation caused by bacterial infection, characterized by persistent infection, excessive bone resorption, and resultant bone defects. Currently, mainstream therapies for jaw OM struggle to eradicate persistent infections, avoid antibiotic resistance, and repair infected bone defects, posing a critical challenge in clinical practice. Methods: Herein, the Fe₃O₄@ZIF-8 core–shell nanoparticles (NPs) platform designed for jaw OM treatment consisted of Fe₃O₄ as the core and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Results: The core–shell platform not only integrated the pH-responsive degradation capability of ZIF-8 but also retained the superparamagnetism of Fe₃O₄ NPs. In the acidic, infectious microenvironment, Fe₃O₄@ZIF-8 NPs underwent continuous degradation, releasing Zn²⁺, thereby conferring potent antibacterial activity. The specific antibacterial mechanism of the nanoparticles lies in the fact that high concentrations of Zn²⁺ directly disrupted bacterial cell membranes and inhibited the bacterial heat shock response. This dysregulates bacterial proteostasis, rendering the bacteria more sensitive to external adverse stresses, ultimately leading to bacterial death. With ZIF-8 framework degradation, the encapsulated Fe₃O₄ NPs were released. Under static magnetic field (SMF) synergy, Fe₃O₄ NPs collaborated with Zn²⁺ to promote bone regeneration and repair infected bone defects in jaw OM lesions. Conclusions: As a multifunctional core–shell platform, Fe₃O₄@ZIF-8 NPs meet the dual clinical needs of antibiosis and osteogenesis, offering a promising translational strategy for jaw OM therapy. Full article

During aging, bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) shift their lineage commitment away from osteogenesis and towards adipogenesis, resulting in bone loss and marrow fat accumulation. We previously reported that during osteogenesis, BMSCs activate mitochondrial oxidative phosphorylation (OXPHOS) at least in part by downregulating cyclophilin D (CypD) expression and, consequently, mitochondrial permeability transition pore (MPTP) activity. We also reported that in contrast, during adipogenesis, BMSCs upregulate CypD and MPTP, activate glycolysis and inhibit OXPHOS. To further study the role of CypD in BMSC bioenergetics, adipogenesis and bone marrow fat accumulation, we used CypD loss-of-function (LOF) or gain-of-function (GOF) models in osteo-adipoprogenitors in vitro and in vivo. We found that CypD LOF and GOF are associated with impaired and enhanced BMSC adipogenesis, respectively, both in vitro and in ectopic bone grafts in vivo. In addition, bioenergetic profiling and metabolomic analyses show evidence of corresponding metabolic reprogramming in CypD LOF and GOF cells. In summary, our study demonstrates the role of CypD-regulated mitochondrial metabolism during BMSC adipogenesis, facilitating the understanding of stem cell fate determination and the molecular mechanism of age-related bone loss as well as bone marrow fat accumulation. Full article

Chronic osteomyelitis and infected bone defects are driven by recurrent infection, biofilm persistence, and dysregulated inflammation, but conventional “eradicate bacteria and fill the defect” approaches often fail to restore a regenerative microenvironment. Herein, we review biofilm-associated immune dysfunction in impaired angiogenesis/osteogenesis and summarize biomaterials that couple infection control with tissue regeneration. We integrate representative platforms into a “Time–Space–Control” framework: (i) time-programmed systems that sequence early antibiofilm/antibacterial actions with later pro-angiogenic and osteogenic cues; (ii) space-focused designs that enhance defect localization, penetration, and coverage of infected niches; and (iii) controllable strategies that enable pathology-responsive and/or externally triggered, on-demand modulation. Based on this synthesis, we propose a practical 4P principle to guide programmable therapeutic biomaterials. Overall, explicitly managing timing, localization, and controllability may improve the alignment of antimicrobial therapy, immune reprogramming, and regenerative support for chronic infected bone repair. Full article

Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift in approaches to bone regeneration, highlighting the transformative potential of biofabrication technologies that integrate tissue engineering with personalized regenerative strategies. Three-dimensional (3D) bioprinting technology enables precise control over the architecture and spatial distribution of cellular and biologically active components, facilitating the creation of complex, personalized bone constructs. Central to this process are bioinks and biomaterials that mimic the extracellular matrix (ECM) and provide an optimal microenvironment for cellular function. Despite the substantial body of accumulated data, a comprehensive theoretical framework for functional bone biofabrication has not yet been fully established, emphasizing both the challenges and the innovative potential of the field. This integrative review synthesizes current knowledge on bone biology—from embryogenesis and cell–matrix interactions to molecular and neural regulation—and links it to the opportunities offered by biofabrication. Particular attention is given to bioinks as mediators between cell biology and engineering sciences, as well as to strategies for creating biomimetic ECM, optimizing scaffold design, and guiding future research toward clinically translatable bone regeneration. Full article

Background/Objectives: Nonunion after tibiotalocalcaneal (TTC) arthrodesis remains challenging, especially in revision settings where union rates are substantially lower than in primary procedures. Biological adjuncts are commonly used to enhance healing, yet most described methods employ fibular onlay struts and cancellous autograft. To our knowledge, intramedullary placement of a fibular autograft for ankle fusion has not previously been reported. This study presents a revision of TTC arthrodesis nonunion treated with this technique and summarizes existing evidence on revision ankle arthrodesis, fibular grafting, and bone marrow aspirate concentrate (BMAC). Methods: We report a revision TTC arthrodesis nonunion managed with a decorticated intramedullary fibular autograft spanning the tibiotalar canal, supplemented with cancellous iliac crest autograft and BMAC. A review of PubMed, Scopus, and Google Scholar (search date: 1 September 2025) was performed to identify studies addressing revision ankle fusion, fibular grafting techniques, and BMAC use in foot and ankle arthrodesis. Primary outcomes included union and complications, with CT-based assessment prioritized when available. Results: At 3 months, radiographs and CT demonstrated progressive osseous bridging consistent with fusion; the patient achieved pain-free weight-bearing without complications. Conclusions: Intramedullary fibular autograft in revision TTC arthrodesis is a novel biological-mechanical strategy that leverages endosteal contact and axial stability while augmenting osteogenesis with cancellous autograft and BMAC. The review supports the biological plausibility and safety of this approach and underscores the importance of CT-based assessment. Full article

Background: Medication-related osteonecrosis of the jaw (MRONJ) remains a challenging complication associated with antiresorptive and antiangiogenic therapies, characterized by impaired bone healing, infection, and compromised vascularization. Advanced biomaterials capable of promoting bone regeneration and modulating the local microenvironment are being investigated as potential therapeutic strategies. Graphene-based biomaterials have recently emerged as promising candidates due to their unique physicochemical properties and multifunctional biological effects. Objective: This systematic review aimed to analyze and synthesize current evidence on graphene-based 3D scaffolds and related graphene-based biomaterials for bone regeneration, with particular attention to their potential relevance in MRONJ treatment and prevention. Data Sources: A systematic literature search was conducted in PubMed and Scopus databases, complemented by manual screening of reference lists from relevant publications. Eligibility Criteria: Studies investigating graphene-based scaffolds, composites, or graphene-derived biomaterials for bone regeneration were considered. Experimental in vitro and in vivo studies, as well as translational studies addressing osteogenesis, angiogenesis, antimicrobial activity, immunomodulation, or drug-delivery properties relevant to bone healing and MRONJ, were included. Editorials, conference abstracts, and non-English publications were excluded. Methods: Titles and abstracts were independently screened by the authors, followed by full-text assessment for eligibility. Data regarding scaffold composition, graphene derivatives, biological mechanisms, and regenerative outcomes were qualitatively synthesized due to heterogeneity in study designs and outcome measures. Results: The identified literature highlights the multifaceted role of graphene-based biomaterials in bone regeneration. Graphene and its derivatives enhance osteogenic differentiation, promote angiogenesis, modulate immune responses, and exhibit intrinsic antimicrobial properties. In addition, graphene-based scaffolds provide versatile platforms for drug delivery and photothermal or photodynamic therapeutic strategies. These multifunctional properties may address key pathophysiological mechanisms involved in MRONJ, including impaired bone remodeling, infection control, and tissue regeneration. Limitations: The available evidence is predominantly derived from preclinical studies, with limited direct investigation in MRONJ-specific models and considerable heterogeneity in scaffold design and experimental methodologies. Conclusions: Graphene-based 3D scaffolds represent a promising and versatile platform for bone regenerative strategies potentially applicable to MRONJ management. Further translational research and well-designed preclinical and clinical studies are required to clarify their safety, efficacy, and therapeutic applicability. Registration: This review was conducted according to PRISMA 2020 guidelines. The review protocol was not registered. 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

Advances in regenerative medicine have positioned platelets and their derivatives—including platelet-rich plasma, platelet-rich fibrin, platelet lysate, extracellular vesicles, and purified growth factors—as promising interventions specifically for skin and bone aging, two clinically accessible tissues with robust preclinical and clinical evidence for platelet-derived component-based rejuvenation and regeneration. Because much of the available evidence comes from injury models or age-associated inflammatory/degenerative diseases, we explicitly distinguish pathology-targeted inflammation resolution/repair from rejuvenation under physiological aging. This review summarizes the composition and core bioactivities of platelet-derived products and delineates their putative anti-aging mechanisms, encompassing proangiogenic signaling, immunomodulation, attenuation of oxidative stress, regulation of extracellular matrix turnover, and stimulation of osteogenesis. We further evaluate emerging applications that expand therapeutic performance, such as platelet-mimetic delivery vehicles, engineered and sustained-release formulations, and targeted use of subcellular structures. Evidence from recent preclinical and clinical studies indicates favorable safety profiles and signals of efficacy across cutaneous rejuvenation and skeletal regeneration, while underscoring persistent challenges related to product standardization, dosing, and outcome measures. Collectively, platelet-based therapeutics represent a versatile platform with broad applicability to anti-aging interventions in skin and bone and strong potential for translation through continued bioengineering and clinical validation. However, because most available evidence comes from injury models or age-associated diseases (e.g., photoaging, chronic wounds, osteoarthritis, osteoporosis), direct extrapolation to physiological aging is limited; throughout, we explicitly contrast these contexts, specify their indication-specific endpoints, and summarize the main translational limitations. 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

Midfacial hypoplasia is a developmental defect caused by insufficient growth of the nasal placodes and maxillary prominences. While genetic studies in mice have identified key genes involved in midfacial development, the regulation of these genes during craniofacial development remains poorly understood. In this study, we demonstrate that microRNAs, short non-coding RNAs, play a crucial role in regulating genes involved in midfacial development. We identified 224 genes associated with midfacial malformations in mice. Through bioinformatics analyses, we predicted that several microRNAs, specifically miR-129-5p, miR-381-3p, miR-124-3p, miR-136-5p, miR-448-3p, miR-374, miR-96, and miR-882, could regulate the expression of these genes. Among these, we experimentally focused on the top four candidate microRNAs: miR-129-5p, miR-381-3p, miR-124-3p, and miR-136-5p. Our findings revealed that the overexpression of these microRNAs inhibited cell proliferation and osteogenesis in nasal process mesenchymal cells. These microRNAs regulated genes associated with midfacial malformations in a dose-dependent manner. Taken together, our results emphasize the significance of pathogenic microRNA–gene networks in the cause of midfacial malformations. 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: Despite extensive preclinical evidence that statins enhance osteogenesis and the widespread clinical use of platelet-rich fibrin (PRF), the clinical effectiveness of statin-incorporated PRF (SIM-PRF) in limiting peri-implant crestal bone loss remains insufficiently validated. Objectives: To address the mentioned gap, we integrated in vitro assays on human periodontal ligament stem cells (hPDLSCs) with a controlled clinical trial to test whether SIM-PRF reduces early and 12-month marginal bone loss versus PRF alone and PRF with bone graft. Methods: In vitro, cytotoxicity, migration and osteogenic differentiation were assessed, in addition to the effect on basal inflammatory markers. Clinically, 24 immediate-implant cases were randomized to receive PRF, PRF+SIM, or PRF+bone graft, with CBCT-based crestal bone change measured at 0–3, 3–6, and 6–12 months. Results: Flow cytometry confirmed the mesenchymal identity of the isolated hPDLSCs, which exhibited dose-dependent responses to SIM treatment. Lower SIM concentrations (0.1 μM) enhanced osteogenic differentiation, as evidenced by increased mineralization, alkaline phosphatase activity, and expression of osteogenic markers (RUNX2 and osteocalcin), while maintaining cell viability and migration. Both SIM concentrations (0.1 μM and 1 μM) significantly reduced basal pro-inflammatory cytokine expression (TNF-α and IL-6). Radiographic analysis revealed significantly reduced crestal bone loss (p < 0.001) in the PRF-SIM and PRF-Bone groups compared to PRF alone, particularly during early postoperative intervals (0–3 and 3–6 months). Notably, no significant difference was observed between the PRF-SIM and PRF-Bone groups (p > 0.05) in preserving the peri-implant bone. Conclusions: These findings highlight the potential of SIM-loaded PRF as an effective, biocompatible, and patient-friendly approach to enhance bone regeneration and implant success. Full article