Search Results (1,262)

Porous Ti-6Al-4V scaffold materials can be used to heal massive bone defects because they can provide space for vascularisation and bone formation. During new bone tissue development, rapid vascular ingrowth into scaffold materials is very important. Osteoblast-derived exosomes are capable of facilitating angiogenesis–osteogenesis coupling. Low-intensity pulsed ultrasound (LIPUS) is a physical therapy modality widely utilised in the field of bone regeneration and has been proven to enhance the production and functionality of exosomes on two-dimensional surfaces. The impact of LIPUS on exosomes derived from osteoblasts cultured in three dimensions remains to be elucidated. In this study, exosomes produced by osteoblasts on porous Ti-6Al-4V scaffold materials under LIPUS and non-ultrasound stimulated conditions were co-cultured with endothelial cells. The findings indicated that the exosomes were consistently and stably taken up by the endothelial cells. Compared to the non-ultrasound group, the LIPUS group facilitated endothelial cell proliferation and angiogenesis. After 24 h of co-culture, the migration ability of endothelial cells in the LIPUS group was 17.30% higher relative to the non-ultrasound group. LIPUS may represent a potentially viable strategy to promote the efficacy of osteoblast-derived exosomes to enhance the angiogenesis of porous Ti-6Al-4V scaffold materials. Full article

Degenerative scoliosis (DS), encompassing conditions like spondylolisthesis and spinal stenosis, is a common type of spinal deformity. Lumbar interbody fusion (LIF) stands as a conventional surgical intervention for this ailment, aiming at decompression, restoration of intervertebral height, and stabilization of motion segments. Despite its widespread use, the precise mechanism underlying spinal fusion remains elusive. In this review, our focus lies on endochondral ossification for spinal fusion, a process involving vertebral development and bone healing. Endochondral ossification is the key step for the successful vertebral fusion. Endochondral ossification can persist in hypoxic conditions and promote the parallel development of angiogenesis and osteogenesis, which corresponds to the fusion process of new bone formation in the hypoxic region between the vertebrae. The ideal material for interbody fusion cages should have the following characteristics: (1) Good biocompatibility; (2) Stable chemical properties; (3) Biomechanical properties similar to bone tissue; (4) Promotion of bone fusion; (5) Favorable for imaging observation; (6) Biodegradability. Utilizing cartilage-derived bone-like constructs holds promise in promoting bony fusion post-operation, thus warranting exploration in the context of spinal fusion procedures. Full article

Alveolar bone remodeling during the retention phase is essential for successful orthodontic treatment. Pulsed electromagnetic field (PEMF) therapy is an adjunctive therapy for bone-related diseases that induces osteogenesis and prevents bone loss. This study aimed to examine the role of PEMF exposure during the retention phase of orthodontic treatment in alveolar bone remodeling. A total of 36 male Wistar rats were divided into control, PEMF 7, and PEMF 14 groups; a 50 g force nickel–titanium closed-coil spring was inserted to create mesial movement in the first molar for 21 d. Furthermore, the spring was removed, and the interdental space was filled with glass ionomer cement. Concurrently, rats were exposed to a PEMF at 15 Hz with a maximum intensity of 2.0 mT 2 h daily, for 7 and 14 days. Afterwards, the cements were removed and the rats were euthanized on days 1, 3, 7, and 14 to evaluate the expression of Wnt5a mRNA and the levels of RANKL, OPG, ALP, and Runx2 on the tension side. The data were analyzed with ANOVA and post hoc tests, with p < 0.05 declared statistically significant. PEMF exposure significantly upregulated Wnt5a mRNA expression, OPG and ALP levels, and Runx2 expression, and decreased RANKL levels in the PEMF 7 and 14 groups compared to the control group (p < 0.05). This study showed that PEMF exposure promotes alveolar bone remodeling during the orthodontic retention phase on the tension side by increasing alveolar bone formation and inhibiting resorption. Full article

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with the physiological responses analyzed. Vasoconstriction was mediated by an increase in the transient receptor protein channels (TRPs), transient receptor potential ankyrin 1 (TRPA1; p = 0.012), and transient receptor potential melastatin 8 (TRPM8; p < 0.001), within cortical defects, enhancing the sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p < 0.01) and vascular endothelial growth factor expression (VEGF; p < 0.001), promoting angiogenesis, vital for bone regeneration. The increased expression of osteogenic proteins peroxisome proliferator-activated receptor gamma coactivator (PGC-1α; p = 0.039) and RNA-binding motif protein 3 (RBM3; p < 0.008) suggests that the reparative processes have been stimulated. Enhanced osteoblast differentiation and the presence of alkaline phosphatase (ALP) at day 5 (three-fold, p = 0.021) and 10 (two-fold, p < 0.001) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.019), indicating the presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy’s multifaceted effects on bone repair, offering insights for therapeutic strategies. Full article

Background/Objectives: In children, an association exists between muscle and bone, as well as between physical activity and osteogenesis. Impact loading is a factor in increasing bone accrual during growth. In this work, we explored the muscle–bone association in girls exposed to long-term physical activity at different levels of impact loading. Methods: Four groups of girls aged 7–16 were considered. The curricular (C; n = 22) group only had curricular physical activity at school (2 h/w). In addition to curricular physical activity, the girls in the dance (D; n = 21), gymnastics at lower training (GL; n = 14), and gymnastics at higher training (GH; n = 20) groups had 2 h/w, 4 h/w, and 4 h/w < training ≤ 12 h/w additional physical activity, respectively, for at least one year. A visual analysis estimated the respective amounts of impact-loading activity. The bone mineral content (BMC), areal bone mineral density (aBMD), and fat-free soft tissue mass (FFSTM) were assessed with dual-energy X-ray absorptiometry. Results: The results showed that, after adjusting for several confounders, statistically significant correlations were present between muscle mass and several bone mineral variables. A regression analysis confirmed the correlation in the data, and showed the marginal role of other body composition variables and physical activity for predicting BMC and BMD. Conclusion: Skeletal muscle mass is a major determinant of the BMC and BMD of the TBLH, as well as of the Appendicular level, in girls exposed to different amounts of long-term impact-loading physical activity. Full article

P-15 is a 15-amino-acid-long biomimetic peptide widely demonstrated to enhance osteogenesis in vivo. Despite the prevalence of polyether-ether-ketone (PEEK) in interbody device manufacturing, a growing body of evidence suggests it may produce an unfavorable immune response. The purpose of this preliminary study was to characterize the immune response and new bone growth surrounding PEEK implants with and without a P-15 peptide-based osteobiologic. A bilateral femoral defect model was conducted using New Zealand white rabbits. A total of 17 test subjects received one implant in each distal femur, either with or without bone graft material. Animals were allowed to survive to 4 or 8 weeks, at which time the femurs were collected and subjected to micro-computer tomography (microCT) or cytokine analysis. MicroCT analysis included the quantification of bone growth and density surrounding each implant. The cytokine analysis of periprosthetic tissue homogenates included the quantification of interleukins (ILs) and TNF-α expression via ELISA kits. Improvements in bone volume were observed in the P-15 cohort for the regions of interest, 500–136 and 136–0 µm from the implant surface, at 8 weeks post-op. Concentrations of IL-1β, IL-4, and IL-6 cytokines were significantly higher in the P-15 cohort compared to the PEEK cohort at the 4-week timepoint. Significant reductions in the concentrations of IL-4 and IL-6 cytokines from the 4- to 8-week cohort were observed in the P-15 cohort only. The P-15 peptide has the potential to modulate the immune response to implanted materials. We observed improvements in bone growth and a more active micro-environment in the P-15 cohort relative to the PEEK control. This may indicate an earlier transition from the inflammatory to remodeling phase of healing. Full article

Introduction: Osteogenesis imperfecta (OI) is a hereditary disorder primarily caused by mutations in type I collagen genes, resulting in bone fragility, deformities, and functional limitations. Studies on upper extremity deformities and associated functional impairments in OI are limited. This cross-sectional study aimed to evaluate upper extremity deformities and functional outcomes in OI. Methods: We included patients regardless of their OI subtypes with a minimum age of 7 years. Radiographic analysis of radial head dislocation, ossification of the interosseous membrane, and/or radioulnar synostosis of the forearm were performed, and deformity was categorized as mild, moderate, or severe. Clinical evaluation was performed using the Quick Disabilities of Arm, Shoulder, and Hand (qDASH) questionnaire and shoulder-elbow-wrist range of motion (ROM). Three-dimensional motion analysis of the upper limb was conducted using the Southampton Hand Assessment Procedure (SHAP). The SHAP quantifies execution time through the Linear Index of Function (LIF) and assesses the underlying joint kinematics using the Arm Profile Score (APS). Additionally, the maximum active Range of Motion (aRoM) was measured. Results: Fourteen patients aged 8 to 73 were included. Radiographic findings revealed diverse deformities, including radial head dislocation, interosseous membrane ossification, and radioulnar synostosis. Six patients had mild, six moderate, and two severe deformities of the upper extremity. Severe deformities and radial head dislocation correlated with compromised ROM and worse qDASH scores. The qDASH score ranged from 0 to 37.5 (mean 11.7). APS was increased, and LIF was reduced in OI-affected persons compared with non-affected peers. APS and LIF also varied depending on the severity of bony deformities. aRoM was remarkably reduced for pro-supination. Conclusion: Patients with OI showed variable functional impairment from almost none to severe during daily life activities, mainly depending on the magnitude of deformity in the upper extremity. Larger multicenter studies are needed to confirm the results of this heterogeneous cohort. Level of evidence: Retrospective clinical study; Level IV. Full article

(1) Background: This systematic review critically appraises and synthesizes evidence from in vitro studies investigating the effects of curcumin nanoparticles on titanium surface modification, focusing on cell adhesion, proliferation, osteogenic differentiation, and mineralization. (2) Methods: A comprehensive electronic search was conducted in PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar databases, yielding six in vitro studies that met the inclusion criteria. The search strategy and study selection process followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A qualitative methodological assessment was performed using the SciRAP (Science in Risk Assessment and Policy) method, which evaluated the reporting and methodological quality of the included studies. (3) Results: All six studies consistently demonstrated that curcumin-coated titanium surfaces inhibited osteoclastogenesis and promoted osteogenic activity, evidenced by enhanced cell adhesion, proliferation, osteogenic differentiation, and mineralization. The mean reporting quality score was 91.8 (SD = 5.7), and the mean methodological quality score was 85.8 (SD = 10.50), as assessed by the SciRAP method. Half of the studies used hydroxyapatite-coated titanium as a control, while the other half used uncoated titanium, introducing potential variability in baseline comparisons. (4) Conclusions: This systematic review provides compelling in vitro evidence supporting the osteogenic potential of curcumin nanoparticle-coated titanium surfaces. The findings suggest that this surface modification strategy may enhance titanium implants’ biocompatibility and osteogenic properties, potentially improving dental and orthopedic implant outcomes. However, the review highlights significant heterogeneity in experimental designs and a concentration of studies from a single research group. Further research, particularly in vivo studies and clinical trials from diverse research teams, is essential to validate these findings and comprehensively understand the translational potential of this promising surface modification approach. Full article

In adverse environments, fine dust is linked to a variety of health disorders, including cancers, cardiovascular, neurological, renal, reproductive, motor, systemic, and respiratory diseases. Although PM10 is associated with oral inflammation and cancer, there is limited research on biomaterials that prevent damage caused by fine dust. In this study, we evaluated the effects of biomaterials using microRNA profiling, flow cytometry, conventional PCR, immunocytochemistry, Alizarin O staining, and ELISA. Compared to SBE (Scutellaria baicalensis extract), the preventive effectiveness of SBEIEs (SBE-induced exosomes) against fine dust was approximately two times higher. Furthermore, SBEIEs promoted cellular differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts, periodontal ligament cells (PDLCs), and pulp progenitor cells (PPCs), enhancing immune modulation for oral health against fine dust. In terms of immune modulation, SBEIEs activated the secretion of cytokines such as IL-10, LL-37, and TGF-β in T cells, B cells, and macrophages, while attenuating the secretion of MCP-1 in macrophages. MicroRNA profiling revealed that significantly modulated miRNAs in SBEIEs influenced four biochemical categories: apoptosis, cellular differentiation, immune activation, and anti-inflammation. These findings suggest that SBEIEs are an optimal biomaterial for developing oral health care products. Additionally, this study proposes functional microRNA candidates for the development of pharmaceutical liposomes. Full article

Some cancers have a poor prognosis and often lead to local recurrence because they are resistant to available treatments, e.g., glioblastoma. Attempts have been made to increase the sensitivity of resistant tumors by targeting pathways involved in the resistance and combining it, for example, with radiotherapy (RT). We have previously reported that treating glioblastoma stem cells with an Nrf2 inhibitor increases their radiosensitivity. Unfortunately, the application of drugs can also affect normal cells. In the present study, we aim to investigate the role of the Nrf2 pathway in the survival and differentiation of normal human adipose-derived stem cells (ADSCs) exposed to radiation. We treated ADSCs with an Nrf2 inhibitor and then exposed them to X-rays, protons or carbon ions. All three radiation qualities are used to treat cancer. The survival and differentiation abilities of the surviving ADSCs were studied. We found that the enhancing effect of Nrf2 inhibition on cell survival levels was radiation-quality-dependent (X-rays > proton > carbon ions). Furthermore, our results indicate that Nrf2 inhibition reduces stem cell differentiation by 35% and 28% for adipogenesis and osteogenesis, respectively, using all applied radiation qualities. Interestingly, the results show that the cells that survive proton and carbon ion irradiations have an increased ability, compared with X-rays, to differentiate into osteogenesis and adipogenesis lineages. Therefore, we can conclude that the use of carbon ions or protons can affect the stemness of irradiated ADSCs at lower levels than X-rays and is thus more beneficial for long-time cancer survivors, such as pediatric patients. Full article

Background: Obesity poses a significant global health challenge, given its association with the excessive accumulation of adipose tissue (AT) and various systemic disruptions. Within the adipose microenvironment, expansion and enrichment with immune cells trigger the release of inflammatory mediators and growth factors, which can disrupt tissues, including bones. While obesity’s contribution to bone loss is well established, the direct impact of obese AT on osteoblast maturation remains uncertain. This study aimed to explore the influence of the secretomes from obese and lean AT on osteoblast differentiation and activity. Methods: SAOS-2 cells were exposed to the secretomes obtained by culturing human subcutaneous AT from individuals with obesity (OATS) or lean patients, and their effects on osteoblasts were evaluated. Results: In the presence of the OATS, mature osteoblasts underwent dedifferentiation, showing an increased proliferation accompanied by a morphological shift towards a mesenchymal phenotype, with detrimental effects on osteogenic markers and the calcification capacity. Concurrently, the OATS promoted the expression of mesenchymal and adipogenic markers, inducing the formation of cytoplasmic lipid droplets in SAOS-2 cells exposed to an adipogenic differentiation medium. Additionally, TGF-β1 emerged as a key mediator of these effects, as the OATS was enriched with this growth factor. Conclusions: Our findings demonstrate that obese subcutaneous AT promotes the dedifferentiation of osteoblasts and increases the adipogenic profile in these cells. Full article

Osteoporosis and other degenerative bone diseases pose significant challenges to global healthcare systems due to their prevalence and impact on quality of life. Current treatments often alleviate symptoms without fully restoring damaged bone tissue, highlighting the need for innovative approaches like stem cell therapy. Adipose-derived mesenchymal stem cells (ADMSCs) are particularly promising due to their accessibility, abundant supply, and strong differentiation potential. However, ADMSCs tend to favor adipogenic pathways, necessitating the use of differentiation inducers (DIs), three-dimensional (3D) hydrogel environments, and photobiomodulation (PBM) to achieve targeted osteogenic differentiation. This study investigated the combined effects of osteogenic DIs, a fast-dextran hydrogel matrix, and PBM at specific wavelengths and fluences on the proliferation and differentiation of immortalized ADMSCs into osteoblasts. Near-infrared (NIR) and green (G) light, as well as their combination, were used with fluences of 3 J/cm², 5 J/cm², and 7 J/cm². The results showed statistically significant increases in alkaline phosphatase levels, a marker of osteogenic differentiation, with G light at 7 J/cm² demonstrating the most substantial impact on ADMSC differentiation. Calcium deposits, visualized by Alizarin red S staining, appeared as early as 24 h post-treatment in PBM groups, suggesting accelerated osteogenic differentiation. ATP luminescence assays indicated increased proliferation in all experimental groups, particularly with NIR and NIR-G light at 3 J/cm² and 5 J/cm². MTT viability and LDH membrane permeability assays confirmed enhanced cell viability and stable cell health, respectively. In conclusion, PBM significantly influences the differentiation and proliferation of hydrogel-embedded immortalized ADMSCs into osteoblast-like cells, with G light at 7 J/cm² being particularly effective. These findings support the combined use of 3D hydrogel matrices and PBM as a promising approach in regenerative medicine, potentially leading to innovative treatments for degenerative bone diseases. Full article

Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA_(BMP-2)/CS_(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA_(BMP-2)/CS_(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration. Full article

The rising demand for effective bone regeneration has underscored the limitations of traditional methods like autografts and allografts, including donor site morbidity and insufficient biological signaling. This review examines nanoparticles (NPs) in tissue engineering (TE) to address these challenges, evaluating polymers, metals, ceramics, and composites for their potential to enhance osteogenesis and angiogenesis by mimicking the extracellular matrix (ECM) nanostructure. The methods involved synthesizing and characterizing nanoparticle-based scaffoldsand integrating hydroxyapatite (HAp) with polymers to enhance mechanical properties and osteogenic potential. The results showed that these NPs significantly promote cell growth, differentiation, and bone formation, with carbon-based NPs like graphene and carbon nanotubes showing promise. NPs offer versatile, biocompatible, and customizable scaffolds that enhance drug delivery and support bone repair. Despite promising results, challenges with cytotoxicity, biodistribution, and immune responses remain. Addressing these issues through surface modifications and biocompatible molecules can improve the biocompatibility and efficacy of nanomaterials. Future research should focus on long-term in vivo studies to assess the safety and efficacy of NP-based scaffolds and explore synergistic effects with other bioactive molecules or growth factors. This review underscores the transformative potential of NPs in advancing BTE and calls for further research to optimize these technologies for clinical applications. Full article

The incidence of osteoporosis in children is increasing because of the increased survival rate of children with chronic diseases and the increased use of bone-damaging drugs. As childhood bone fragility has several etiologies, its management requires a thorough evaluation of all potentially contributing pathogenetic mechanisms. This review focuses on the main causes of primary and secondary osteoporosis and on the benefits and limits of the different radiological methods currently used in clinical practice for the study of bone quality. The therapeutic and preventive strategies currently available and the most novel diagnostic and treatment strategies are also presented. Optimal management of underlying systemic conditions is key for the treatment of bone fragility in childhood. DXA still represents the gold standard for the radiologic evaluation of bone health in children, although other imaging techniques such as computed tomography and ultrasound evaluations, as well as REMS, are increasingly studied and used. Bisphosphonate therapy is the gold standard for pharmacological treatment in both primary and secondary pediatric osteoporosis. Evidence and experience are building up relative to the use of monoclonal antibodies such as denosumab in cases of poor response to bisphosphonates in specific conditions such as osteogenesis imperfecta, juvenile Paget’s disease and in some cases of secondary osteoporosis. Lifestyle interventions including adequate nutrition with adequate calcium and vitamin D intake, as well as physical activity, are recommended for prevention. Full article