Search Results (1,498)

Platelet-rich plasma (PRP) is widely used as a second-line treatment for chronic tendinopathy that persists despite structured conservative care, yet outcomes and imaging correlates remain heterogeneous. This review outlines PRP biology and preparation, summarises quantitative imaging techniques for monitoring tendon response, and presents the experience of a single centre integrating these methods into routine supraspinatus and lateral elbow PRP workflows. PRP is described as an autologous platelet concentrate with variable leukocyte and fibrin content, with leukocyte-rich formulations commonly selected for chronic tendinopathy. Quantitative approaches—including ultrasound shear-wave elastography and radiomics, MRI T2/T2* mapping, CT-based bone metrics, PET/CT, and optical techniques—offer numerical biomarkers of tendon structure, mechanics, and inflammation but are rarely implemented in PRP trials. At the authors’ centre, leukocyte-rich PRP is injected under ultrasound guidance after failed physiotherapy, and follow-up combines validated questionnaires with grey-level run-length matrix texture analysis of ultrasound and 3.0 T MRI T2 distribution profiling. A pilot ultrasound study in supraspinatus and common extensor tendinosis showed uniform short-term clinical improvement and significant changes in most texture features, with selected parameters correlating with symptom relief. A prospective supraspinatus cohort demonstrated significant six-month clinical gains in both tendinosis and small partial-thickness tears, whereas only the tendinosis group exhibited T2 profile convergence toward asymptomatic patterns. These data indicate that quantitative ultrasound radiomics and whole-length T2 profiling are feasible imaging biomarkers that capture PRP-induced tendon remodelling beyond qualitative imaging and may help tailor PRP protocols to specific tendon phenotypes. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by persistent joint inflammation and systemic immune dysregulation. While bone marrow activation has been linked to RA pathogenesis, direct access to bone marrow tissue for progenitor analysis remains limited by ethical and technical constraints. Analysis of progenitor cells in peripheral blood can serve as a surrogate reflecting bone marrow activation. In this study, we analysed peripheral blood cells from 12 RA patients and 9 healthy controls using high-dimensional spectral flow cytometry with a nine-marker panel (CD45, CD31, CD235, CD133, CD34, CD105, CD271, CD90, PDPN). Flow Self-Organizing Map (FlowSOM) clustering identified 20 distinct cell populations. Additionally, a complementary flow cytometry panel was used to assess CD31 expression on immune subsets in peripheral mononuclear cells (PBMCs) from 9 RA and 9 healthy donors of this cohort. RA patients showed increased CD45⁺CD31⁻ immune cells, but not their putative progenitors. Conversely, putative CD45⁺CD31^int progenitors and CD45⁺CD31^int mature cells were reduced, along with CD31 expression on T cells. Levels of CD235a⁺ putative erythroid precursors and CD45⁺CD31⁺ progenitors were significantly increased in RA patients. Three putative stromal cell populations were detected in circulation. Together, these findings reveal expanded erythroid precursor populations and reduced CD31 expression on T cells in RA. Our data underscore broad systemic alterations in cellular homeostasis in RA patients. In conclusion, our results suggest that the loss of CD31 expression on immune cell precursors plays a role in age-associated immune remodelling and immune activation in RA and provides the rationale for further studies on erythroblast differentiation and the functional role of erythroblasts in chronic inflammation. Full article

Bioactive glass (BAG) S53P4 is a clinically approved bone substitute with antibacterial, osteoconductive and osteostimulatory properties. Its antibacterial effect is associated with ion release, local pH elevation and osmolality, but the precise biochemical and biophysical mode-of-action is unclear. This study investigates the antibacterial mechanism of BAG S53P4 eluates. BAG eluates, collected at 2, 4, 8, and 24 h, eradicated Staphylococcus aureus. Elemental analysis revealed an early increase in concentrations of Si and Na, a later rise in Ca, depletion of P over time and rapid loss of Mg. Membrane disturbances occurred within 5 min, evident by permeability for SYTOX, aligning with time-kill kinetics for S. aureus and Bacillus subtilis. In B. subtilis, 2h-BAG-eluate induced rapid delocalization of marker proteins for cell division and DNA repair, signaling membrane potential collapse and nucleoid condensation. Transcriptomics revealed early transcription remodeling reflecting ionic and energetic imbalance, including disruption of central metabolism, redox homeostasis, and translational stability. Scanning electron microscopy revealed severe cell surface damage and particulate deposits on S. aureus. Transmission electron microscopy showed cell envelop disruptions and cytoplasmic leakage. Energy dispersive X-ray analysis identified Si on bacterial cell surface at 4 h and intracellular accumulation in punctured, empty cells at 24 h. Overall, BAG ionic dissolution products kill bacteria through a stepwise mechanism involving membrane damage, protein delocalization and metabolic impairment, accompanied by Si deposition on bacterial surfaces and loss of Mg. This finally leads to cell wall degradation, cytoplasmic content leakage and further Si deposition on the cells and inside cell ghosts. Full article

Titanium and its alloys are widely used for orthopedic implants, but their intrinsic bioinertness may hinder osseointegration. In this study, titanium dioxide nanotube (TNT) arrays were fabricated on Ti-6Al-4V scaffolds via anodization, and their effects on the adhesion behavior of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Surface characterization showed that anodization successfully generated ordered TNT layers, increased surface roughness, enhanced protein adsorption, and induced an apparent superhydrophilic wetting response. Compared to the untreated scaffold and TNT50, the small-diameter TNT10 surface significantly promoted hBMSC adhesion and proliferation. Microscope imaging further revealed enhanced cell spreading, F-actin organization, and vinculin expression on TNT surfaces, with the most prominent focal adhesion-related staining observed in TNT10. Quantitative proteomic analysis showed that TNT10 was associated with coordinated remodeling of adhesion- and cytoskeleton-related molecular programs, including focal adhesion, cell–substrate junction, and regulation of the actin cytoskeleton. In contrast, TNT50, despite supporting obvious cytoskeletal remodeling, was more compatible with a dynamic, higher-turnover adhesion state. Overall, these findings suggest that small-diameter TNTs provide a more favorable interfacial microenvironment for stable early hBMSC adhesion on porous titanium scaffolds. Full article

Background: The combination of pharmacological therapy and exercise is frequently recommended for osteoporosis management; however, whether antiresorptive agents may interfere with exercise-induced bone adaptation remains unclear. This study aimed to investigate the independent and combined effects of zoledronate and treadmill exercise on bone microarchitecture and mechanical strength in an ovariectomized rat model. Methods: Twenty-four female Sprague Dawley rats underwent ovariectomy and were assigned to four groups: Control, zoledronate (ZA), treadmill exercise (T), and combined zoledronate and exercise (ZA + T). An additional sham-operated group was included. Zoledronate was administered as a single subcutaneous injection, and a 6-week treadmill exercise routine was implemented. Bone microarchitecture was assessed using micro-computed tomography, and a three-point bending test was employed for evaluation of mechanical properties. Results: The combined ZA + T group demonstrated significant improvements in trabecular bone parameters, including bone volume/tissue volume and trabecular number, compared with the Control group. Mechanical strength parameters, including maximum load and stiffness, were also significantly enhanced in the ZA + T group. Cortical bone parameters exhibited no significant changes. Conclusions: Treadmill exercise did not attenuate the effects of zoledronate, and may offer additive benefits in enhancing trabecular bone microarchitecture and mechanical strength. These findings suggest that exercise therapy can complement bisphosphonate treatment and contribute to optimizing therapeutic strategies for osteoporosis, supporting the potential utility of combined pharmacological and exercise-based interventions for improving bone health. Full article

Current evidence suggests that achieving the desired level of osseointegration necessitates a hierarchical approach to implant design. This is particularly relevant for osseointegration around implant systems such as those presenting vertical decompression chambers and acid-etched surfaces which could further be augmented by non-thermal plasma (NTP) treatment. Three implant systems were compared in this study: (i) ND (GM Helix Acqua Implant; Neodent^®, Curitiba, PR, Brazil—hybrid, acid-etched thread design treated with isotonic sodium chloride solution), (ii) Sin (Epikut Plus; S.I.N. Implant System, São Paulo, Brazil—V-shaped, acid-etched thread design treated with nano-hydroxyapatite), and (iii) Mp (Maestro; Implacil De Bortoli, São Paulo, Brazil—buttress, acid-etched thread design with decompressing vertical chambers). The ND and Sin implants were used directly as supplied by the manufacturer. For the Mp implants, the manufacturer-supplied surface was subjected to supplemental acid etching with 37% hydrochloric acid followed by Argon-based NTP treatment administered with a pulsed plasma generator prior to implantation into the iliac crest of n = 12 adult female sheep. Histomorphometric analysis was conducted at 3- and 12-week post-implantation (n = 6 sheep per time point) to assess bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). After 3 weeks in vivo, the healing chambers of all implant groups consisted predominantly of newly forming woven bone. By 12 weeks, bone maturation was observed, with the presence of remodeling sites and some areas of well-organized lamellar structures occupying the healing chambers. At both 3 and 12 weeks, the Mp implants demonstrated significantly higher BAFO values relative to ND (p = 0.015 and p = 0.008, respectively). The combination of vertical healing chambers, acid etching, and NTP treatment promoted early vascular infiltration and sustained bone deposition. Full article

Bone regeneration requires tight coordination between mesenchymal stem cells (MSCs), immune signaling, and extracellular matrix remodeling. Yet, how atypical immune receptors contribute to this process remains unclear. Here, we identify Toll-like receptor 10 (TLR10) as a key regulator of osteogenic differentiation in human adipose-derived MSCs. Herein, ASC/TERT1 MSCs were engineered to overexpress or silence TLR10 using lentiviral vectors, and osteogenic differentiation (0–14 days) was assessed by metabolic assays—RT-qPCR of COL1A2, ALPL and BGLAP—Alizarin Red S staining, and quantitative mass spectrometry. Enhancing TLR10 expression promoted osteogenic gene programs, extracellular matrix organization, metabolic adaptation, and robust matrix mineralization, whereas TLR10 suppression maintained proliferative states and impaired osteoblast maturation. Proteomic analyses revealed that TLR10 selectively activates osteogenic, ECM-remodeling, and vitamin D-responsive pathways, while restraining programs antagonistic to differentiation. Notably, active vitamin D induced TLR10 expression and partially restored osteogenesis in TLR10-deficient cells, indicating that TLR10 is associated with vitamin D-driven bone formation. Together, beyond its established role in innate immunity, TLR10 emerges as a vitamin D-responsive regulator of mesenchymal stem cell osteogenesis, highlighting a potential therapeutic axis to enhance bone regeneration and osteogenic outcomes. Full article

Background: Individuals with type 1 diabetes (T1D) have an increased fracture risk, but no clear biomarkers have been linked to this risk. ApoA1 and ApoB were selected due to their association with metabolic disturbances in T1D. Copeptin was included given emerging evidence that ADH influences bone remodeling and glucose metabolism. The aim of this study was to identify biomarkers associated with fractures in patients with T1D. Methods: This prospective, population-based study included 473 individuals with T1D and 465 individuals without diabetes. Fasting blood samples were collected at baseline, and fracture outcomes were assessed after approximately 10 years. ApoA1, ApoB, CRP, GFR, copeptin, and HbA1c were analyzed. Cox regression was used to evaluate associations with fracture risk, and results were calculated per unit increase. Results: In total, 91 fractures occurred. A Kaplan–Meier analysis was performed to compare fracture risk between the control group and individuals with T1D. The results demonstrated a higher risk of fractures over time in patients with T1D compared to controls (p-value 0.037). When we divided the population by patient/control status, we found that, after adjustment for all investigated variables (HbA1c, GFR, CRP, copeptin, age, smoking, cortisone treatment, physical activity, lipid-lowering medication, and gender), both ApoA1 (HR 4.290, CI 1.871–9.837, p-value < 0.001) and ApoB (HR 7.625, CI 1.995–29.138, p-value 0.003) remained independently associated with fracture risk in the T1D group. Conclusions: Higher ApoA1 and ApoB levels are associated with increased fracture risk in individuals with T1D, independently of confounders. Additionally, individuals with T1D have a higher overall fracture risk compared to controls. Full article

Periodontal disease represents a major global health burden, beginning with gingivitis and progressing to periodontitis, which causes connective tissue breakdown, alveolar bone resorption, and eventual tooth loss. Beyond local pathology, periodontitis is a chronic inflammatory condition with systemic associations, including cardiovascular disease, diabetes, and metabolic disorders. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have emerged as promising candidates for periodontal regeneration. This review aimed to map the current evidence on MSC-derived EVs (MSC-EVs) in periodontal regeneration, focusing on their mechanisms of action, therapeutic potential, and translational challenges. A comprehensive literature search was conducted across a major biomedical database (PubMed) to identify preclinical and clinical studies investigating MSC-EVs in the context of periodontitis. Data were charted on EV cargo composition, biological functions, regenerative outcomes, and reported limitations. Evidence indicates that MSC-EVs encapsulate bioactive molecules—including antimicrobial peptides, proteins, lipids, and microRNAs—that modulate immune responses, suppress pro-inflammatory signaling, and promote angiogenesis and tissue repair. In periodontal models, MSC-EVs attenuate osteoclast activity, enhance fibroblast proliferation, and stimulate extracellular matrix remodeling, supporting regeneration of periodontal ligament and alveolar bone. Exosome-based approaches demonstrate advantages such as reduced immunogenicity, improved safety, and feasibility for storage and standardization. However, most findings remain preclinical, with limited human data available. To bridge the translational gap, well-designed clinical trials are needed to confirm efficacy and safety while addressing regulatory challenges, GMP standards, and outcome measures. Harnessing their regenerative capacity while mitigating side effects may guide precision-targeted therapies, and continued mechanistic studies with standardized production will be key to advancing MSC-EVs into clinical practice. Full article

Objective: Back pain is a multifactorial condition commonly associated with degenerative spinal changes. Spondylophytes are frequent outgrowths of the vertebral bodies that may be influenced by arterial hypertension via a possible increased pulsation of the aorta and its effects on bone remodeling. If it can be demonstrated that an increased pulse pressure in the aorta due to hypertension promotes the growth of spondylophytes and thereby increases the likelihood of back pain, future studies may investigate how the effectiveness of blood pressure management can be improved in order to reduce the prevalence of degenerative changes in the spine and, consequently, prevent back pain. This study investigated the association between arterial hypertension and thoracic spondylophyte formation using whole-body MRI data from the population-based Study of Health in Pomerania (SHIP). Materials and Methods: Spondylophyte presence and area were assessed for their association with hypertension status in 859 SHIP-START-3 participants who underwent whole-body MRI. Right-sided spondylophytes at T8-T11 were measured on axial T2-weighted sequences. Hypertension was defined by self-report or antihypertensive medication use; a sensitivity analysis was conducted using the 2024 European Society of Cardiology definition (systolic blood pressure ≥ 140 mmHg). Multivariate regression models adjusted for age, sex, obesity, and smoking were used to assess associations. Machine learning algorithms were applied for validation. Results: Spondylophytes were present in 87.7% of participants. Hypertension was significantly associated with spondylophyte presence (OR = 2.07, 95% CI: 1.15–3.81) but not consistently associated with spondylophyte size. Spondylophyte size increased from T8 to T11, and was associated with age, male sex, and obesity. Sensitivity analyses widely confirmed robustness of the analysis. Conclusions: This population-based MRI study investigates the still insufficiently studied relationship between arterial hypertension and the formation of thoracic spondylophytes. The findings are consistent with the hypothesis that hypertension may be associated with spinal bone remodelling, though causal inference remains limited by the cross-sectional study design. Further longitudinal studies are needed to clarify causality and clinical relevance for spinal degeneration and back pain. Full article

Bone marrow-derived mesenchymal stem cells (BMSCs), owing to their osteoblastogenic differentiation potential, are crucial for maintaining bone homeostasis and remodeling. Nevertheless, in aging and age-related bone diseases like osteoporosis, BMSCs show significantly diminished osteogenic potential, with a concomitant increase in adipogenic differentiation. The aged BMSCs also become desensitized to BMP2 stimulation to a large extent and exhibit aberrations in BMP2 signaling. However, the molecular mechanisms facilitating this shift in lineage commitment and mediating the cellular dysfunctions remain elusive. This knowledge gap hinders the development of regenerative strategies for skeletal aging and osteoporosis. This study employed an integrative tandem mass tag (TMT)-based phosphoproteomic and total proteomic profiling on BMSCs isolated from young (6-month) and aged (15-month) C57BL/6 (B6) mice to elucidate global alterations in both protein activity and expression. The analysis identified more than 500 proteins that underwent significant alterations (BH-adjusted p-value <0.05) either in phosphorylation or expression between young and aged BMSCs. Many lineage-specific markers also underwent changes in both phosphorylation and expression with aging. Additionally, key biological processes, including cellular metabolism, clathrin-mediated endocytosis, and nucleocytoplasmic transport mechanisms, were enriched for the deregulated proteins. Signaling proteins, ERK-1/2, had increased activating phosphorylation in the aged BMSCs, while transcription factors Lrrfip1, Ruvbl1, and Ruvbl2 also exhibited dysregulated activity and abundance in the aged BMSCs. The findings from the study adds significant mechanistic insights into how aging disrupts signal transduction, metabolism, and transcriptional program in BMSCs, contributing to age-associated loss of bone mass and reduced skeletal regenerative capabilities. Through the identification of key mediators of BMSC dysfunction seen in aging, this work offers a strong foundation in devising potential therapeutic strategies to restore diminished osteogenic potential and treat osteoporosis. Full article

Clinically, bone mineral density (BMD) accounts for only approximately 50% of the observed variance in bone fragility fractures. This review examines the dynamic and mechanistic role of the non-collagenous organic matrix, specifically proteoglycans (PGs) and glycosaminoglycans (GAGs), in maintaining bone toughness and bone quality. During aging, bulk cortical GAG levels decrease by up to ~17% and are highly associated with reduced bone tissue toughness. We analyze how this age-related loss may arise from uncoupled bone remodeling and tissue aging, including the accumulation of older, interstitial tissue and dysregulated osteocyte-mediated matrix maintenance. We then discuss the functional importance of PG/GAG composition, maturation, and catabolism and how perturbations in these processes can promote pro-inflammatory signaling that accelerates matrix degradation and contributes to systemic aging. Lastly, we discuss potential interventions to preserve or restore GAGs/PGs in bone and improve overall bone quality. Full article

Background: Atrophy of the alveolar ridge in the posterior maxilla often requires sinus floor elevation prior to implant placement. Photobiomodulation using low-level laser therapy (LLLT) has been suggested as a supportive approach for bone healing, although data based on histological evaluation are still limited. Methods: This study presents histological and radiological secondary outcomes of a randomized clinical trial on bone regeneration after lateral window sinus augmentation. Twenty patients were allocated according to grafting material (allogeneic or xenogeneic) and the use of adjunctive LLLT. After 6 months, bone core biopsies were obtained at the time of implant placement and processed for histological analysis. Radiological bone gain was assessed using CBCT. Results: Bone gain was achieved in all groups, allowing implant placement in every case. Mean bone gain reached 7.53 ± 3.32 mm in LLLT-treated sites and 7.02 ± 2.00 mm in controls, with no statistically significant differences. Histological analysis confirmed trabecular bone formation across all groups. Mild inflammatory cell infiltrates were observed more frequently in LLLT-treated sites (p = 0.029), although this finding was not associated with impaired tissue organization or compromised healing. Conclusions: Both allogeneic and xenogeneic grafts showed good biocompatibility and supported effective bone regeneration after sinus augmentation. The addition of photobiomodulation did not demonstrate statistically significant clinical or radiological benefits within this exploratory cohort, but it may be associated with subtle differences in tissue remodeling. Full article

Temporomandibular disorders (TMDs) are multifactorial conditions traditionally attributed to excessive mechanical loading on the temporomandibular joint, leading to clinical manifestations ranging from joint sounds to structural deformation. Contributing factors include trauma, occlusal abnormalities, psychological stress, and bruxism. However, immune and molecular alterations associated with early disease activity are not systematically integrated into structure-centered TMD frameworks. Emerging evidence indicates that temporomandibular joint osteoarthritis (TMJOA) involves activation of innate immunity caused by damage-associated molecular patterns (DAMPs) generated through mechanical loading, together with non-antigen-specific adaptive immune responses, including macrophage polarization and T helper 17 (Th17) and regulatory T (Treg) cell imbalance. Inflammatory and mechanical inputs converge through shared signaling modules and mechanoresponsive transcriptional programs, promoting extracellular matrix degradation, fibrotic remodeling, and subchondral bone remodeling. This review synthesizes the current immunopathological and mechanobiological evidence and introduces temporomandibular immunologic disease (TMID) as a mechanism-oriented framework, characterized by a reinforcing cycle between mechanically induced tissue damage and immune activation within the temporomandibular joint (TMJ) microenvironment. TMID complements TMJOA and Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) structural diagnostic categories while excluding antigen-specific autoimmune arthritides such as rheumatoid arthritis, thus functioning as a mechanistic overlay framework for the integration of immuno-mechanical signaling networks in immune-active, mechanically driven TMJ pathology. Full article

Local antibiotic delivery has gained a central role as an adjunct to radical debridement in chronic osteomyelitis, allowing high antimicrobial concentrations at the infection site while reducing systemic toxicity. This narrative review summarizes the current clinical evidence on commercially available antibiotic-loadable bone substitutes, with particular focus on calcium sulfate (CaSO₄)-based systems and biphasic calcium sulfate/hydroxyapatite (CaS/HA) composites. Nineteen studies were included. Differences in formulation, resorption kinetics, antibiotic elution profile and osteoconductive behavior are discussed, alongside clinical outcomes including recurrence of infection, reoperation rates and complication patterns. Finally, based on the currently available evidence and expert recommendations, practical guidance is proposed to support carrier selection in different clinical scenarios (cavitary vs. corticomedullary defects; high-risk soft tissue; polymicrobial or resistant infections). Across published series, although heterogeneous, infection eradication rates are generally high when local carriers are integrated into structured surgical protocols. Calcium sulfate carriers provide rapid resorption and robust early antibiotic release but are associated with higher rates of sterile wound drainage. In contrast, CaS/HA biocomposites demonstrate more gradual remodeling and radiographic integration, potentially improving defect consolidation and reducing wound-related morbidity, although leakage and cost considerations remain relevant. Full article