Search Results (1,505)

Rheumatoid arthritis (RA) is a systemic autoimmune disease in which persistent synovitis drives interconnected cartilage degradation, bone erosion, and functional decline. Conventional synthetic, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) remain the foundation of RA management. Hydrogel-based local therapy should therefore be positioned as an adjunct for selected joints rather than as a substitute for systemic disease control. Hydrogels provide a versatile local materials platform because their injectability, tunable crosslinking, tissue retention, stimulus-responsive release, interfacial adhesion, lubrication, and extracellular matrix-mimetic properties can be tailored to the inflamed joint microenvironment. This narrative, evidence-graded review evaluates local hydrogel therapies using two complementary frameworks: the synovium–cartilage–bone pathological axis and a materials-science chain linking composition and crosslinking to structure and properties, release and degradation, and tissue-level outcomes. Evidence is classified as direct RA evidence, transferable evidence from related disease or tissue-engineering models, or conceptual evidence from mechanistic and materials-science studies. Therapeutic outcomes are separately graded as local immunomodulation, structural protection, tissue repair, or functionally validated structural disease modification. Current preclinical evidence supports the use of hydrogels for sustained local delivery and synovial immunomodulation, while selected systems demonstrate cartilage-protective or anti-erosive effects. However, durable multitissue restoration accompanied by functional recovery remains insufficiently demonstrated. Future studies should prioritize RA-relevant long-term models, in vivo intra-articular pharmacokinetics and biodistribution, standardized structural and functional endpoints, repeat-dose safety, and evaluation as add-on therapy to systemic DMARDs. Full article

Th17 cells play an important role in adaptive immunity and inflammation; however, the mechanisms regulating their migration into inflammatory tissues are not fully understood. In this study, we found that ex vivo human effector/memory but not central/memory Th17 cells express and use the discoïdin domain receptor 1 (DDR1) to migrate in collagen gels. The tyrosine kinase activity of DDR1 is essential to this process since its blockade with the DDR1 kinase inhibitor 7rh and the DDR1 kinase-dead construct inhibited the migration of human Th17 cells. Our results indicated that the DDR1 kinase activity enhanced Th17 cell migration by activating the MAPK/ERK pathway. We then examined the role of DDR1 in the inflammatory model of collagen-induced arthritis (CIA). Treatment of CIA mice with the DDR1 kinase inhibitor 7rh led to reduced arthritis severity, synovial inflammation and cartilage destruction. DDR1 expression is higher on T cells isolated from CIA mice than on those from naïve mice, and its blockade inhibited Th17 cell infiltration into the joints, which was associated with the inhibition of IL-17 levels. Along these lines, isolated T cells from 7rh-treated arthritic mice showed a drastic reduction in migration in collagen gels compared to those isolated from control arthritic mice. Further, the 7rh treatment reduced the levels of TNF-α and IL-1β and increased the levels of IL-10, thus promoting an anti-inflammatory environment. Our findings provide an important role for the DDR1 tyrosine kinase in promoting Th17 cell infiltration into inflammatory tissues, especially in collagen-rich tissues like the joints, and in the development of arthritis. Full article

Musculoskeletal (MSK) disorders—osteoporosis, osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, tendinopathy, and skeletal muscle injury—contribute the largest share of years lived with disability worldwide. Conventional therapy relies on systemic dosing or repeated intra-articular and peri-tissue injections, which suffer from off-target toxicity, poor lesional bioavailability, and low adherence. Polymer microneedles (MNs)—micron-scale projections of biodegradable, dissolving, hydrogel-forming, or composite polymers—have rapidly matured into a versatile platform for minimally invasive, spatially localized, and temporally programmable delivery of small molecules, biologics, nucleic acids, extracellular vesicles, and cells to MSK tissues. This review synthesizes 2018–2026 advances in polymer MN systems engineered specifically for MSK regeneration. We classify dominant polymer chemistries and MN architectures; map fit-for-purpose across bone, cartilage, joint, intervertebral disc, tendon, and skeletal muscle; and survey “smart” MN designs that exploit reactive oxygen species, pH, mechanical, triboelectric, optogenetic, and ultrasonic triggers. We close with a concise conclusion and forward perspective that identifies the key design levers—hybrid MN–scaffold combination products, stimuli-responsive platforms tuned to the MSK micro-environment, and cell- and EV-loaded formats—most likely to have clinical impact. Full article

Arthritis is a chronic inflammatory disease characterized by progressive joint damage, in which oxidative stress and exacerbated immune responses play a critical role. Synbiotics, defined as a combination of probiotics and prebiotics, may enhance these beneficial effects; however, their efficacy depends on maintaining microbial viability throughout gastrointestinal transit. In this study, we evaluated the anti-inflammatory and antioxidant effects of Levilactobacillus brevis LBH1070. Lacticaseibacillus paracasei ATCC 334 and phenylbutazone (PBZ) were used as probiotic and allopathic drug controls, respectively. Both probiotic strains significantly reduced paw edema by 46%, comparable to PBZ (45%), and decreased lipid oxidation (33–36%) and protein oxidation (40–45%), thereby preserving the integrity of the popliteal lymph node, the lymph node closest to the edema site. Furthermore, L. paracasei ATCC 334 and L. brevis LBH1070 reduced total T helper CD4+ lymphocyte infiltration in the popliteal lymph node by 44–54% and decreased IL-1β-producing T helper lymphocytes by 77–78%, surpassing the effect of PBZ (49%). TNF-α-producing T lymphocytes were also reduced by 60–62%, compared to PBZ (53%). These findings highlight the potential of L. brevis LBH1070, its synbiotic formulation, and L. paracasei ATCC 334 as complementary treatments to modulate immune responses and oxidative stress during arthritis. Full article

Background/Objectives: Intra-articular injections are used for temporomandibular disorders (TMDs) resistant to conservative treatment. However, many reviews assess injectable agents combined with arthrocentesis or other co-interventions, limiting interpretation of their standalone effects. This overview aimed to summarize meta-analytic evidence on standalone intra-articular injections for temporomandibular joint disorders. Methods: MEDLINE, BASE, and Europe PMC were searched on 29 March 2026. Systematic reviews with quantitative meta-analyses evaluating standalone intra-articular TMJ injections were included. Data regarding injectable substances, clinical indications, and outcome domains were extracted and synthesized descriptively. Results: Three systematic reviews with meta-analyses were included. The evidence addressed platelet-rich plasma, corticosteroids, sodium hyaluronate, and physiological saline. Reported indications included degenerative joint disease, osteoarthritis, internal derangement, and arthritis. All included agents were reported to be associated with pain reduction. Conclusions: Meta-analytic evidence on standalone intra-articular injections for TMDs remains limited and heterogeneous. Available data suggest potential benefits, mainly for pain reduction, but do not establish clear superiority of any agent. The potential therapeutic activity of physiological saline should be considered when designing future injection trials. Full article

Rheumatoid arthritis (RA) is a systemic rheumatic disease. Its most prominent characteristic is synovitis, which manifests clinically as arthritis, resulting in joint damage. Interstitial lung disease (ILD) is an extraarticular manifestation of RA that hinders therapeutic goals, affects life prognosis, and can be worsened by the administration of disease-modifying antirheumatic drugs (DMARDs). Therefore, proper management of ILD, including consideration of risk factors such as the systemic disease activity of RA and autoantibodies, and early detection with high-resolution computed tomography are required at the introduction of DMARDs. Methotrexate, a class of DMARD used as the anchor drug for RA treatment, has been recognized as likely to worsen RA-ILD. However, there are currently reports suggesting that methotrexate may have beneficial effects on RA-ILD. Conversely, several studies have also shown exacerbations of ILD with the administration of biological DMARDs, which are thought of as tolerable for patients with RA-ILD. Rheumatologists should be wary of emergence or changes in the activity of ILD and arthritis during treatment of any kind with DMARDs. Further studies are warranted to clarify underlying ethnic factors, such as the possible effects of antimelanoma differentiation-associated gene 5 antibodies on RA-ILD. Full article

Background/Objectives: The aim of this study is to analyze outcomes in patients who underwent genicular artery embolization (GAE) with respect to pain, symptoms, physical activity, quality of life, and knee joint range of motion and muscle strength of the knee joint. The study will provide evidence of the treatment’s effectiveness using both subjective and objective measurements. In addition, the study will examine the impact of the severity of radiological changes in the knee joint and the number of embolized vessels on the extent of improvement in outcomes following the procedure. Methods: Patients eligible for GAE who exhibited symptoms of chronic exudative knee arthritis, confirmed by USG and MRI with contrast, did not have laboratory markers of inflammation, nor did they respond effectively to standard non-surgical treatments. The analysis included 34 patients. Subjective parameters were assessed using the VAS and KOOS scales. Knee range of motion and muscle strength were assessed using an electronic dynamometer and goniometer. Measurements were performed according to the same schedule before GAE, and at 1, 3 and 6 months after the procedure. The results were subjected to statistical analysis. Results: In the analysis up to 6 months, a significant time effect was demonstrated for the VAS and all KOOS subscales. The improvement was visible after 1 month and continued after 3 and 6 months. No significant changes over time were demonstrated for objective parameters. Exploratory analysis demonstrated a relationship between increased knee extensor strength and pain reduction up to 3 months and increased range of motion up to 6 months after the GAE. There was no significant association between radiological changes and the number of embolized vessels with improved outcomes after GAE. Conclusions: GAE appears to be a promising minimally invasive treatment option for patients with chronic knee synovitis. Clinically meaningful improvements were observed in patient-reported outcomes. Full article

Osteoarthritis (OA) is a disabling joint disease characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Furthermore, catabolic inflammatory processes as well as dysregulated cellular signalling and oxidative stress are central to OA pathogenesis. Despite its growing global burden, currently available therapies primarily provide symptomatic relief and fail to target underlying molecular mechanisms and halt disease progression. Cold atmospheric plasma (CAP), a partially ionised, non-thermal gas that generates controlled reactive oxygen and nitrogen species (RONS), has emerged as a promising therapeutic modality capable of modulating redox-sensitive signalling pathways. CAP has demonstrated the capacity to suppress pro-inflammatory cytokine expression, enhance antioxidant defence mechanisms, influence macrophage polarisation, and stimulate tissue repair processes in rheumatoid arthritis, diabetic and dermal wound healing models. However, its potential as a disease-modifying therapy for the treatment of OA is not yet fully understood and warrants further experimental investigation. This review explores current pre-clinical evidence from different disease models, which may have implications for the potential application of CAP as a therapeutic intervention for OA, either as a disease-modifying therapy or as an adjuvant therapy for intra-articular drug delivery. Furthermore, key translational challenges including plasma parameter standardisation, interactions with synovial fluid and optimisation of joint-specific delivery strategies are discussed, identifying gaps that require further experimental investigation. Collectively, the findings of this review highlight CAP as a promising multimodal therapy with translational potential for the treatment of OA warranting further experimental validation and may open innovative avenues for future research. Full article

Background/Objectives: The interplay between oral and systemic diseases is highlighted by the shared inflammatory mechanisms and epidemiological associations between periodontitis and rheumatoid arthritis (RA). Building on previous syntheses of the effect of periodontal therapy on RA disease activity, we sought to refine the evidence base through strict restriction to randomized controlled trials (RCTs), separate analysis of the two non-interchangeable formulations of the Disease Activity Score on 28 joints (DAS28-CRP and DAS28-ESR, based on either C-reactive protein or erythrocyte sedimentation rate, respectively), and inclusion of recent randomized trials. We aimed to determine whether the first two steps of periodontal therapy (steps 1 and 2 of the 2020 EFP S3-level clinical practice guideline), delivered through supragingival professional mechanical plaque removal and subgingival instrumentation, reduce DAS28 in adults with concurrent RA and periodontitis. Methods: The review protocol was registered in PROSPERO (CRD420261400735). Five databases were searched in accordance with PRISMA 2020. Only RCTs were eligible. Risk of bias was assessed with RoB-2. DAS28-CRP and DAS28-ESR were analyzed in separate random-effects forest plots. Sensitivity analyses addressed adjunctive antibiotics and high baseline disease activity. Results: Ten trials (n = 430 randomized patients) were included. At 3 months, DAS28-CRP was significantly reduced (between-group MD = −0.84, 95% CI −1.38 to −0.29; change-from-baseline MD = −0.55, −0.92 to −0.19). On DAS28-ESR at 3 months, the change-from-baseline estimate was significant (MD = −1.27, −2.22 to −0.31) and the follow-up estimate concordant in direction but not significant (MD = −0.89, −1.85 to 0.07), with substantial heterogeneity. Conclusions: Periodontal therapy may be associated with short-term reductions in RA disease activity, particularly DAS28-CRP at 3 months, with directionally concordant but less certain effects on DAS28-ESR. The evidence remains limited by small sample sizes, risk of bias, substantial heterogeneity of the DAS28-ESR estimates, and sparse follow-up beyond 3 months. As no trial reported individual responder categories, these group-level findings support periodontal therapy as a possible adjunctive measure in RA rather than a predictable, clinically meaningful benefit at the individual patient level. Full article

Background/Objectives: Patellofemoral joint (PFJ) replacement is a bone-preserving option for isolated patellofemoral osteoarthritis; however, reported survivorship and failure patterns remain variable. This study evaluated implant survivorship, functional outcomes, reoperations, and failure mechanisms following PFJ replacement using standard second-generation implant systems, with or without patellar resurfacing. Methods: We retrospectively reviewed a consecutive cohort of 39 patients (48 knees) who underwent PFJ replacement for isolated patellofemoral osteoarthritis between 2011 and 2021. Median age at surgery was 59 years, and median body mass index (BMI) was 31 kg/m². Median follow-up for clinical and revision surveillance was 9 years (IQR 8–10). Functional outcomes were assessed using the Oxford Knee Score (OKS) and SF-12 Physical and Mental Component Scores (PCS and MCS). Implant survivorship was analyzed using Kaplan–Meier methodology, with conversion to total knee arthroplasty (TKA) as the endpoint. Statistical analyses were primarily descriptive and exploratory because only five TKA revisions occurred. Results: Median OKS improved from 19 (IQR 16–24) preoperatively to 36 (IQR 24–42) at the latest follow-up, with a median paired improvement of 17 points. SF-12 PCS improved from 25 to 47, and SF-12 MCS from 36 to 55. Eight knees (16.7%) underwent non-revision reoperation, and five knees (10.4%) underwent conversion to TKA. All TKA revisions were performed for the progression of tibiofemoral osteoarthritis. Kaplan–Meier survivorship free from TKA revision was 89.6% at 9 years (95% CI 76.8–95.5). No clear difference in TKA-free survivorship was detected between resurfaced and non-resurfaced knees. Conclusions: PFJ replacement demonstrated substantial functional improvement and mid- to long-term survivorship comparable to published registry ranges in a selected cohort with isolated patellofemoral osteoarthritis. TKA revision was uncommon and was attributable to the progression of tibiofemoral osteoarthritis. Because of the retrospective design, small cohort size, bilateral cases, and limited number of revision events, subgroup and risk-factor analyses should be interpreted as exploratory. Full article

Rheumatoid arthritis (RA) is an autoimmune disease primarily characterized by chronic, erosive polyarthritis. It is associated with a high rate of disability, and its pathogenesis remains incompletely understood. Uncontrolled chronic inflammation, synovial hyperplasia, Pannus formation, and bone destruction in RA patients remain the core challenges facing current clinical treatment, and the inflammatory response is generally considered the initiating factor for this series of pathological processes. In an inflammatory environment, the body’s metabolic rate accelerates, leading to increased local oxygen consumption and ultimately creating a hypoxic microenvironment. Research has shown that under hypoxic conditions, glycolysis serves as the body’s primary energy pathway and is essential for sustaining the inflammatory response. Furthermore, lactate, a byproduct of glycolysis, functions not only as a metabolic byproduct but also as a precursor molecule; through lactylation, it contributes to the progression of RA. Although this metabolic–epigenetic axis is a common feature of various chronic inflammatory diseases, its effects on joint pathology may contribute to RA progression. Therefore, this article focuses on the intrinsic connections among hypoxia, glycolysis, and lactylation, and systematically reviews the immunological and inflammatory mechanisms of glycolysis in RA, the relationship between glycolysis and synovial hyperplasia, Pannus formation, and bone destruction in RA, and the role of lactate modification in promoting the pathological progression of RA. It also summarizes the latest research advances in RA therapies targeting hypoxia, glycolysis, and lactate modification, aiming to provide a theoretical basis for a deeper understanding of the pathogenesis of RA and the development of targeted treatment strategies. Full article

Background/Objectives: Rheumatoid arthritis (RA) has been associated with accelerated atherosclerosis and cerebrovascular alterations. Our 2017 study compared 60 RA patients to healthy controls, assessing vascular, neurological, and cognitive parameters. The present study is a follow-up of these RA patients to evaluate disease progression and vascular changes over time, using their 2017 results as baseline. Methods: In 2023, we reassessed 43 of the original 60 RA patients using laboratory testing, carotid ultrasound, functional transcranial Doppler (TCD) and brain magnetic resonance imaging (MRI) examinations. Changes over time were analyzed within the same individuals. Results: Inflammatory markers and lipid profiles showed a trend toward improvement, though changes were not statistically significant, except for a significant increase in vitamin D (p < 0.001) and a decrease in Disease Activity Score in 28 Joints (DAS28) scores (p < 0.001). Carotid ultrasound revealed a significant increase in plaque burden (p = 0.022 on the right side and p = 0.008 on the left), while carotid intima media thickness (cIMT) showed a non-significant rise. TCD measurements indicated significantly increased pulsatility (p < 0.001 on the right, p = 0.001 on the left side) and resistance (p = 0.001 on the right, p = 0.012 on the left side) indices and reduced flow velocities (p < 0.001 on the right and p = 0.001 on the left side) in bilateral middle cerebral arteries (MCAs). The cerebrovascular reserve capacity was significantly lower on the right side overall (p = 0.013), with further decline noted in the methotrexate (MTX)-treated subgroup on the left side (p = 0.043). MRI findings showed non-significant numerical trends toward worsening lacunar small-vessel disease (p = 0.405) and cerebral atrophy (p = 0.063), with higher but stable lacunar infarction scores among MTX users (p = 0.023). Conclusions: Despite improved inflammatory control, RA patients demonstrated progressive vascular and hemodynamic alterations over time, while MRI changes should be interpreted as trends. These findings support multimodal vascular monitoring in RA. Full article

Spondyloarthritis associated with inflammatory bowel diseases (IBD-SpA), also known as enteropathic arthritis, is an independent entity belonging to the spondyloarthritis (SpA) group. In recent years, a great amount of new data has been published regarding the pathogenesis and treatment of the disease. In this narrative review we present the main pathogenetic pathways along the gut–joint axis, the genetics of IBD and SpA, the role of environmental factors and that of the microbiome, as well as the main immunopathological processes including immune cells and inflammatory mediators. We cover the clinical picture, the specifics of axial and peripheral SpA-IBD, and briefly discuss the diagnostics. There are common options in the pharmacotherapy of SpA and IBD; however, some drugs that control arthritis (e.g., NSAIDs, IL-17 inhibitors) might not be suitable for the treatment of IBD. Based on the pathogenetic role of the microbiome, it is suggested that pharmacotherapy can be supplemented with non-pharmacological remedies, such as diet including the administration of short-chain fatty acids (SCFAs). Finally, we briefly look at the future that might include rational, even personalized treatment. Full article

Background: Rheumatoid arthritis (RA) is a persistent autoimmune condition defined by widespread synovial tissue inflammation and structural joint deterioration, with an estimated global prevalence between 0.5% and 3%. The disease predominantly targets synovial joints, resulting in progressive functional impairment when therapeutic intervention is delayed or inadequate. Objective: This review aims to comprehensively examine the contributing risk factors, underlying pathophysiological processes, and recently developed immunoengineering-based therapeutic strategies applicable to the clinical management of rheumatoid arthritis. Methods: A structured review of peer-reviewed literature was undertaken through PubMed, utilizing a targeted search strategy incorporating the terms ‘rheumatoid arthritis’ and ‘immunoengineering.’ Filters were applied to restrict results to English-language publications from peer-reviewed sources. The review emphasized studies investigating genetic susceptibility, environmental determinants, immune cell behaviour, and novel therapeutic advances in RA management. Results: Multiple interdependent risk factors underpin RA development, most notably genetic variants including HLA-DRb1 alleles, alongside demographic influences such as biological sex and advancing age, as well as obesity and pathogenic microbial exposure. These factors collectively initiate a self-amplifying inflammatory process characterized by protein citrullination and the subsequent generation of anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF). The ensuing immune dysregulation—driven principally by monocyte and T-lymphocyte infiltration—propagates synovial inflammation and progressively destroys cartilaginous and bony structures. Conclusions: While considerable progress has been achieved in RA pharmacotherapy, existing treatments remain constrained by systemic side effects and incomplete therapeutic responses. Emerging immunoengineering strategies offer a targeted approach to modulating the molecular and immunological milieu of affected joints, providing improved therapeutic precision. Continued investigation in this area is anticipated to yield novel clinical pathways capable of substantially enhancing patient outcomes in rheumatoid arthritis care. Full article

Background/Objectives: The aim of this study was to develop and validate a high-frequency ultrasound radiomics-based model for quantitative assessment of metacarpophalangeal (MCP) joint cartilage damage in early rheumatoid arthritis (RA). Methods: 656 MCP joints from 99 early RA patients and 65 healthy controls were prospectively enrolled and graded according to the Outcome Measures in Rheumatology (OMERACT) system. After radiomics feature extraction, five machine learning classifiers were evaluated. Radiomics, clinical, and combined models were constructed and assessed. Radiomics scores were compared among healthy grade 0 joints, early RA grade 0 joints stratified into two risk subgroups, and RA grade ≥ 1 joints. SHapley Additive exPlanations (SHAP) analysis was used for interpretation. Results: Eight stable radiomics features were selected. Among classifiers, support vector machine achieved the highest cross-validated performance and was selected as the final radiomics classifier (validation AUC = 0.804). The combined model, integrating radiomics features with age, disease duration, and Disease Activity Score in 28 joints, achieved the best diagnostic performance (AUC = 0.855), significantly outperforming both the radiomics and clinical models. Among OMERACT grade 0 joints, the high-risk subgroup demonstrated elevated radiomics-derived scores. SHAP analysis identified original_shape2D_PerimeterSurfaceRatio as the strongest contributor. Conclusions: High-frequency ultrasound radiomics combined with clinical features demonstrated strong performance in detecting MCP joint cartilage damage in early RA and may provide a quantitative extension to conventional semiquantitative assessment. Full article