Search Results (3,075)

Electrospun nanofibrous membranes have gained considerable attention in bone tissue engineering due to their ability to mimic the extracellular matrix and provide a suitable environment for cell attachment and proliferation. This study investigates the fabrication, characterization, and biocompatibility of poly(L-lactic acid) (PLA)-based membranes enhanced with periclase (MgO) and gold nanoparticles (AuNPs). The membranes were fabricated using an optimized electrospinning process and subsequently characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FT-IR), and contact angle measurements. Additionally, in vitro biodegradation studies in simulated body fluid (SBF) and cytocompatibility tests with osteoblast-like cells were conducted. The results demonstrated that the incorporation of MgO and AuNPs significantly influenced the structural and chemical properties of the membranes, improving their wettability and bioactivity. SEM imaging confirmed uniform fiber morphology with well-distributed nanoparticles. FT-IR spectroscopy indicated successful integration of bioactive components into the PLA matrix. Cytocompatibility assays showed that modified membranes promoted higher osteoblast adhesion and proliferation compared to pristine PLA membranes. Furthermore, biodegradation studies revealed a controlled degradation rate suitable for guided bone regeneration applications. These findings suggest that electrospun PLA membranes enriched with MgO and AuNPs present a promising biomaterial for GBR applications, offering improved bioactivity, mechanical stability, and biocompatibility. Full article

A thermosensitive collagen-based gel (TSV gel), containing type I and III collagen, has been developed to improve the handling and stability of bone graft materials. However, its direct effect on osteoblasts is not well understood. This in vitro study evaluated the biological response of human oral osteoblasts to four bone substitutes: OsteoBiol^® GTO^® (larger granules with 20% TSV gel), Gen-OS^® (smaller granules), Gen-OS^® combined with 50% TSV gel (Gen-OS^®+TSV), and TSV gel alone. Cell proliferation, adhesion, morphology, collagen and calcium deposition, alkaline phosphatase (ALP) activity, gene expression of osteogenic markers and integrins, and changes in pH and extracellular calcium and phosphate levels were investigated. All materials supported osteoblast activity, but Gen-OS+TSV and GTO showed the most pronounced effects. These two groups promoted better cell adhesion and proliferation, higher ALP activity, and greater matrix mineralization. GTO improved cell adhesion, while the addition of TSV gel to Gen-OS enhanced biological responses compared with Gen-OS alone. Integrins α2, α5, β1, and β3, important for cell attachment to collagen, were notably upregulated in Gen-OS+TSV and GTO. Both groups also showed increased expression of osteogenic markers such as BMP-2, ALP, and osteocalcin (OCN). Higher extracellular ion concentrations and a more alkaline pH were observed, particularly in conditions without cells, suggesting active ion uptake by osteoblasts. In conclusion, combining TSV gel with collagen-based granules improves the cellular environment for osteoblast activity and may support bone regeneration more effectively than using either component alone. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Heterotopic ossification (HO) refers to the pathological formation of bone in soft tissues, typically following trauma, surgical procedures, or as a result of genetic disorders. Notably, injuries to the central nervous system significantly increase the risk of HO, a condition referred to as neurogenic HO (NHO). This review outlines the cellular and molecular mechanisms driving HO, focusing on the inflammatory response, progenitor cell reprogramming, and current treatment strategies. HO is primarily fuelled by a prolonged and dysregulated inflammatory response, characterized by sustained expression of osteoinductive cytokines secreted by M1 macrophages. These cytokines promote the aberrant differentiation of fibro-adipogenic progenitor cells (FAPs) into osteoblasts, leading to ectopic mineralization. Additional factors such as hypoxia, BMP signalling, and mechanotransduction pathways further contribute to extracellular matrix (ECM) remodelling and osteogenic reprogramming of FAPs. In the context of NHO, neuroendocrine mediators enhance ectopic bone formation by influencing both local inflammation and progenitor cell fate decisions. Current treatment options such as nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, and surgical excision offer limited efficacy and are associated with significant risks. Novel therapeutic strategies targeting inflammation, neuropeptide signalling, and calcium metabolism may offer more effective approaches to preventing or mitigating HO progression. Full article

Titanium–aluminum–vanadium (Ti6Al4V) is a material chosen for spine, orthopedic, and dental implants due to its combination of desirable mechanical and biological properties. Lasers have been used to modify metal surfaces, enabling the generation of a surface on Ti6Al4V with distinct micro- and nano-scale structures. Studies indicate that topography with micro/nano features of osteoclast resorption pits causes bone marrow stromal cells (MSCs) and osteoprogenitor cells to favor differentiation into an osteoblastic phenotype. This study examined whether the biological response of human MSCs to Ti6Al4V surfaces is sensitive to laser treatment-controlled micro/nano-topography. First, 15 mm diameter Ti6Al4V discs (Spine Wave Inc., Shelton, CT, USA) were either machined (M) or additively manufactured (AM). Surface treatments included no laser treatment (NT), nanosecond laser (Ns), femtosecond laser (Fs), or nanosecond followed by femtosecond laser (Ns+Fs). Surface wettability, roughness, and surface chemistry were determined using sessile drop contact angle, laser confocal microscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Human MSCs were cultured in growth media on tissue culture polystyrene (TCPS) or test surfaces. On day 7, the levels of osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), and vascular endothelial growth factor 165 (VEGF) in the conditioned media were measured. M NT, Fs, and Ns+Fs surfaces were hydrophilic; Ns was hydrophobic. AM NT and Fs surfaces were hydrophilic; AM Ns and Ns+Fs were hydrophobic. Roughness (Sa and Sz) increased after Ns and Ns+Fs treatment for both M and AM disks. All surfaces primarily consisted of oxygen, titanium, and carbon; Fs had increased levels of aluminum for both M and AM. SEM images showed that M NT discs had a smooth surface, whereas AM surfaces appeared rough at a higher magnification. Fs surfaces had a similar morphology to their respective NT disc at low magnification, but higher magnification revealed nano-scale bumps not seen on NT surfaces. AM Fs surfaces also had regular interval ridges that were not seen on non-femto laser-ablated surfaces. Surface roughness was increased on M and AM Ns and Ns+Fs disks compared to NT and Fs disks. OCN was enhanced, and DNA was reduced on Ns and Ns+Fs, with no difference between them. OPN, OPG, and VEGF levels for laser-treated M surfaces were unchanged compared to NT, apart from an increase in OPG on Fs. MSCs grown on AM Ns and Ns+Fs surfaces had increased levels of OCN per DNA. These results indicate that MSCs cultured on AM Ns and AM Ns+Fs surfaces, which exhibited unique roughness at the microscale and nanoscale, had enhanced differentiation to an osteoblastic phenotype. The laser treatments of the surface mediated this enhancement of MSC differentiation and warrant further clinical investigation. Full article

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion. Full article

Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article

Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article

Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article

Porosity and roughened surfaces of implant materials have been shown to lead to improved cellular attachment and enhanced osseointegration. These topography changes in the surface also aid in the mechanical interlocking of the material to the bone. Polyetheretherketone (PEEK) has emerged as a popular alternative to titanium-based implants due to its lack of stress-shielding effect, radiolucency, and high chemical resistance. However, PEEK is bioinert, thus requiring surface modifications to elicit appropriate cellular responses that lead to successful osteointegration of the material in vivo. Sulfonation is a process used to modify the surface of PEEK, which can be controlled by varying parameters such as soak time and soak temperature, thereby fabricating a porous surface on the material. This work aimed to ensure the repeatability of a previously optimized sulfonated and hydrothermally treated PEEK surface and subsequently observe the mechanical properties, bacterial attachment, and cellular response of pre-osteoblast MC3T3-E1 cells on the surface. This study found that while all PEEK surfaces had similar cell and Staphylococcus aureus attachment, the sulfonated and hydrothermally treated PEEK (peak mean load of 605 N, p ≤ 0.0001) and the sulfonated only PEEK (peak mean load of 495 N, p = 0.0240) had a higher level of performance in expulsion testing than smooth PEEK due to its mechanical interlocking ability. Imaging and contact angle analysis confirm that a surface with repeatable porosity can be achieved. Full article

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

Xylosyltransferase-I (XT-I) plays a crucial role in skeletal development and cartilage integrity. An XT-I deficiency is linked to severe bone disorders, such as Desbuquois dysplasia type 2. While animal models have provided insights into XT-I’s role during skeletal development, its specific effects on adult bone homeostasis, particularly in human mesenchymal stem cell (hMSC) differentiation, remain unclear. This study investigates how XT-I deficiency impacts the differentiation of hMSCs into chondrocytes, osteoblasts, and adipocytes—key processes in bone formation and repair. The aim of this study was to elucidate for the first time the molecular mechanisms by which XT-I deficiency leads to impaired bone homeostasis. Using CRISPR-Cas9-mediated gene editing, we generated XYLT1 knockdown (KD) hMSCs to assess their differentiation potential. Our findings revealed significant disruption in the chondrogenic differentiation in KD hMSCs, characterized by the altered expression of regulatory factors and extracellular matrix components, suggesting premature chondrocyte hypertrophy. Despite the presence of perilipin-coated lipid droplets in the adipogenic pathway, the overall leptin mRNA and protein expression was reduced in KD hMSCs, indicating a compromised lipid metabolism. Conversely, osteogenic differentiation was largely unaffected, with KD and wild-type hMSCs exhibiting comparable mineralization processes, indicating that critical aspects of osteogenesis were preserved despite the XYLT1 deficiency. In summary, these results underscore XT-I’s pivotal role in regulating differentiation pathways within the bone marrow niche, influencing cellular functions critical for skeletal health. A deeper insight into bone biology may pave the way for the development of innovative therapeutic approaches to improve bone health and treat skeletal disorders. Full article

Osteoclastogenesis—the activation and differentiation of osteoclasts—is one of the pivotal processes of bone remodeling and is regulated by RANKL/RANK signaling, the decoy function of osteoprotegerin (OPG), and a cascade of pro- and anti-inflammatory cytokines. The disruption of this balance leads to pathological bone loss in diseases such as osteoporosis and rheumatoid arthritis. FFAR4 (Free Fatty Acid Receptor 4), a G protein-coupled receptor for long-chain omega-3 fatty acids, has been confirmed as a key mediator of metabolic and anti-inflammatory effects. This review focuses on how FFAR4 acts as the selective receptor for the omega-3 fatty acid docosahexaenoic acid (DHA). It activates two divergent signaling pathways. The Gαq-dependent cascade facilitates intracellular calcium mobilization and ERK1/2 activation. Meanwhile, β-arrestin-2 recruitment inhibits NF-κB. These collective actions reshape the cytokine environment. In macrophages, DHA–FFAR4 signaling lowers the levels of TNF-α, interleukin-6 (IL-6), and IL-1β while increasing IL-10 secretion. Consequently, the activation of NFATc1 and NF-κB p65 is profoundly suppressed under TNF-α or RANKL stimulation. Additionally, DHA modulates the RANKL/OPG axis in osteoblastic cells by suppressing RANKL expression, thereby reducing osteoclast differentiation in an inflammatory mouse model. Full article

Bioactive glass materials have been used for decades in orthopedic surgery, traumatology, and oral and maxillofacial surgery to repair bone defects. This study aimed to evaluate in vitro the survival and proliferation of MG63 human osteosarcoma-derived cells on S53P4 bioactive glass (BonAlive^® granules). Microscopic visualization was performed to directly observe the interactions between the cells and the material. Osteoblast-like cells were examined on non-adherent test plates, on tissue culture (TC)-treated plates and on the surface of the bioglass to assess the differences. Cell survival and proliferation were monitored using a CCK-8 optical density assay. Comparing the mean OD of MG63 cells in MEM on TC-treated plates with cells on BG, we detected a significant difference (p < 0.05), over each time of observation. The sustained cell proliferation confirmed the non-cytotoxic property of the bioglass, as the cell number increased continuously at 48, 72, 96, and 168 h and even did not plateau after 168 h. Since the properties of bioglasses can vary significantly depending on their composition and environment, a thorough characterization of their biocompatibility is crucial to ensure their effective and appropriate application—for example, during hip and knee prosthesis insertion. Full article