Search Results (678)

Osteoarthritis (OA) is increasingly recognized as a mechanically driven whole-joint disease in which abnormal mechanotransduction initiates a cascade of mitochondrial dysfunction, chronic inflammation, and progressive cartilage degeneration. Among the mechanosensitive molecules identified to date, Piezo1 has emerged as a key mechanosensitive regulator linking pathological mechanical loading to intracellular calcium signaling and downstream cellular responses. Growing evidence indicates that persistent Piezo1 activation promotes mitochondrial calcium overload, excessive reactive oxygen species production, ATP depletion, mitochondrial membrane depolarization, and impaired mitophagy, ultimately amplifying chondrocyte dysfunction and extracellular matrix degradation. In parallel, mitochondrial damage triggers immunometabolic reprogramming through activation of the cGAS–STING pathway and the NLRP3 inflammasome. It also promotes pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6. Together, these responses may contribute to a self-perpetuating cycle of inflammation and tissue destruction. This review provides a comprehensive synthesis of recent advances regarding the role of Piezo1 in OA, focusing on the mechanistic links between mechanotransduction, mitochondrial dysfunction, mitophagy, and immunometabolic dysregulation. We further discuss the contribution of mitochondrial quality-control pathways, including PINK1/Parkin-, BNIP3-, and FUNDC1-mediated mitophagy, as well as alterations in mitochondrial dynamics involving DRP1, MFN1, MFN2, and OPA1. Emerging experimental models are discussed as valuable tools for accelerating therapeutic discovery. Finally, we critically evaluate current therapeutic strategies targeting the Piezo1–mitochondria axis, including mechanosensitive channel modulation, mitochondrial protection, mitophagy enhancement, gene therapy, biomaterial-assisted delivery, and nanomedicine. Collectively, current evidence supports the Piezo1–mitochondria–immune axis as an important mechanistic framework contributing to OA pathogenesis and as a potential therapeutic target. Integrating mechanobiology, mitochondrial medicine, and precision-engineered experimental models may facilitate the development of next-generation disease-modifying therapies capable of slowing or preventing osteoarthritis progression. Full article

Background: Physical activity is widely recommended for preserving musculoskeletal health and managing osteoarthritis-related pain, although its benefits are commonly framed in terms of muscle strengthening, weight control, and physical performance. This narrative review aimed to examine movement more broadly as a physiological regulator of synovial joint homeostasis, sensory calibration, and functional adaptation. Methods: A structured literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science from database inception to 1 February 2026. Experimental studies, observational studies, clinical trials, systematic reviews, meta-analyses, and selected narrative reviews addressing movement-responsive joint biology or pain regulation were considered. Evidence was synthesized across four interrelated domains: mechanical, fluidic, immune-metabolic, and sensory regulation. Results: The narrative synthesis indicates that the concept of the synovial joint as a dynamic mechano-fluidic organ in which cartilage, synovium, synovial fluid, capsule, subchondral bone, periarticular tissues, and sensory pathways interact continuously. Repeated physiological movement may promote synovial fluid exchange, lubrication, cartilage nutrition, hyaluronic acid and lubricin function, matrix turnover, anti-inflammatory signaling, proprioceptive control, and exercise-induced hypoalgesia. In contrast, inactivity and unloading may impair fluid dynamics, promote muscle inhibition, stiffness, inflammatory persistence, sensory deconditioning, and loss of function. Excessive or poorly distributed loading may also disrupt homeostasis through matrix injury, inflammation, fatigue, and nociceptive sensitization. These findings informed the proposed adaptive loading window, a hypothesis-generating conceptual framework rather than a clinically validated threshold, describing the dynamic range of movement within which joint function and pain regulation may be supported without sustained tissue or symptom aggravation. Conclusions: Movement should be viewed not only as a therapeutic intervention, but also as a continuous regulator of joint biology and perception. Its clinical value may depend on identifying an individualized loading range that supports adaptation, function, and confidence in movement while avoiding both underloading and overload. Full article

Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degeneration, chronic low-grade inflammation, and disruption of tissue homeostasis. Although the mechanosensitive ion channel Piezo1 has been implicated in OA pathogenesis, its expression may also be modulated by inflammatory stimuli independently of applied mechanical loading. This study established a scaffold-free three-dimensional co-culture organoid model comprising human bone marrow-derived mesenchymal stem cell-derived chondrocyte-like cells and M-CSF/RANKL-differentiated RAW264.7-derived osteoclast-like cells to investigate Piezo1-associated molecular responses, inflammatory signaling, and mitophagy-related markers under lipopolysaccharide (LPS)-induced inflammatory conditions. Osteoclast-like differentiation was validated in parallel monolayer cultures by tartrate-resistant acid phosphatase staining and the presence of multinucleated cells before the corresponding differentiated cultures were used for organoid generation. Histological staining, immunofluorescence, CellTiter-Glo 3D viability assay, lactate dehydrogenase cytotoxicity assay, RT-qPCR, and Western blotting were used to evaluate extracellular matrix formation and inflammatory, catabolic, and mitochondrial quality-control-associated markers. LPS stimulation increased the expression of Piezo1, HIF-1α, phosphorylated CaMKII, NLRP3, cleaved Caspase-1, and MMP13, together with alterations in mitophagy- and autophagy-associated markers. Among the evaluated compounds, curcumin produced the greatest improvement in viability relative to the LPS-treated group and was selected for subsequent molecular analyses. Curcumin treatment was associated with reduced inflammatory and catabolic marker expression and partial preservation of cartilage-associated matrix markers. These findings demonstrate inflammation-associated changes in Piezo1 expression and related molecular markers but do not establish mechanically activated Piezo1 signaling or Piezo1-dependent causality. The organoid system therefore represents an exploratory LPS-induced inflammatory model exhibiting selected OA-relevant molecular and matrix-associated features. Full article

Articular cartilage defects remain a significant clinical challenge due to the limited intrinsic regenerative capacity of cartilage and the inability of many current therapeutic approaches to restore the structure and function of native hyaline tissue. As a result, considerable research efforts have been directed toward the development of tissue-engineering and biomaterial-based strategies capable of promoting more effective regeneration. Among these, hydroxyapatite–hydrogel (HAp–hydrogel) composites have emerged as particularly promising candidates because they combine the biological functionality of HAp with the structural versatility of hydrogel networks. Hydrogels provide a highly hydrated, extracellular matrix-like environment that supports cell survival, facilitates matrix deposition, and enables the localized delivery of therapeutic agents. At the same time, their physicochemical properties can be tailored through a variety of crosslinking approaches and advanced responsive design strategies. The incorporation of HAp, either in nano- or microscale form, contributes to mechanical reinforcement, supports subchondral bone regeneration, and influences cellular behavior through both biochemical and mechanotransductive mechanisms. Beyond promoting chondrogenic differentiation, HAp–hydrogel composites have also been investigated for their capacity to modulate inflammation, stimulate angiogenesis within the subchondral region, provide antibacterial protection, and maintain a microenvironment conducive to tissue repair. This review critically examines recent advances in the development and application of HAp–hydrogel composites for cartilage regeneration, highlighting material design principles, fabrication strategies, healing mechanisms, and the key challenges that continue to influence their clinical translation. Full article

By damaging target tissues and compromising the host immune system, Myxobolus cerebralis and Tetracapsuloides bryosalmonae remain persistent threats to salmonids. RNA sequencing was used to assess transcriptome modulation in the kidney and head cartilage (HC) of rainbow trout during single and co-infections with these two myxozoan parasites. Fish were exposed to M. cerebralis (Mc) and T. bryosalmonae (Tb), and 30 days later, half of the fish from each group were subjected to sequential co-infections (Mc⁺ and Tb⁺). This assessment aimed to evaluate the combined effects of both pathogens. Transcriptomic analysis was conducted using kidney and HC tissues collected 60 days post-co-infection. The results showed that infection order altered host transcriptional profiles in a tissue-dependent manner. In the kidney, Tb fish showed pronounced transcriptional alterations linked to chronic inflammation, immune complex clearance, and IL-8-mediated responses. Tb⁺ fish exhibited broad immune activation in the kidney, suggesting dysregulated inflammatory responses likely associated with subsequent infection with M. cerebralis. In the kidney of Mc⁺ fish, the immune response was characterized by macrophage and IL signaling pathways. In HC, Mc fish activated Th17, IL-23, phagolysosome, and IL-6 cytokine pathways. In contrast, Mc⁺ fish showed increased pathogen processing and enhanced metabolic responses accompanied by suppression of cytokines and tissue repair processes. HC responses in Tb⁺ fish shifted toward IL-23, Th17-driven responses, alongside reduced developmental and extracellular matrix processes. The study establishes that host responses to myxozoan co-infection are shaped by tissue tropism and infection sequence, with distinct immune and tissue remodeling pathways activated in the target organs. These findings enhance the understanding of sequential T. bryosalmonae and M. cerebralis infections and provide a basis for identifying tissue-specific biomarkers and key immune targets. The findings may help identify methods for improved monitoring and management of myxozoan infections in salmonids. Full article

Rheumatoid arthritis is a chronic inflammatory joint disease often accompanied by depressive symptoms, in which functional impairment does not always reflect the extent of structural joint damage. Sertraline, a selective serotonin reuptake inhibitor, may influence behavioural and neuroimmune pathways, but its effects on the relationship between joint pathology and functional performance remain unclear. This study evaluated whether sertraline affects functional performance independently of histopathological joint damage in collagen-induced arthritis. Male Wistar rats with collagen-induced arthritis were assigned to untreated or treatment groups receiving sertraline, methotrexate, combined methotrexate and sertraline, infliximab, or tocilizumab. Functional performance was assessed by spontaneous wheel-running activity, body weight, and joint swelling. At week 12, ankle joints underwent histopathological evaluation, and haematological parameters and serum cytokines were analysed. Sertraline did not reduce synovial inflammation, cartilage damage, or bone erosion, although sertraline-treated rats showed a smaller numerical decline in spontaneous wheel-running activity than rats with untreated collagen-induced arthritis. In contrast, methotrexate and biologic therapies improved both structural damage and functional outcomes. Functional performance did not consistently correlate with histopathological severity or circulating cytokine levels. Sertraline did not produce a significant improvement in histopathological outcomes compared with untreated collagen-induced arthritis, while the smaller numerical decline in exploratory wheel-running activity should be interpreted cautiously. Full article

Background/Objectives: Fibroblast-like synoviocytes (FLS) are key contributors to rheumatoid arthritis (RA) pathogenesis, driving synovial inflammation, cartilage degradation, bone erosion and disease persistence. Recent advances have revealed substantial FLS heterogeneity, with distinct fibroblast subsets exhibiting different pathogenic roles within the rheumatoid synovium. Although disease-modifying antirheumatic drugs (DMARDs) constitute the cornerstone of RA treatment, their effects on FLS have not been comprehensively characterised. This review summarises and compares the effects of conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) on RA-FLS. Methods: A non-systematic literature review was conducted to identify studies investigating the effects of DMARDs on RA-FLS. Studies evaluating the impact of csDMARDs, bDMARDs and tsDMARDs on FLS proliferation, apoptosis, migration, invasion, inflammatory mediator production, extracellular matrix remodelling and osteoclastogenic activity were included. Results: Available evidence indicates that DMARDs modulate multiple pathogenic functions of RA-FLS. Methotrexate, leflunomide, hydroxychloroquine and sulfasalazine regulate inflammatory signalling, apoptosis, autophagy and ferroptosis. Biologic agents, particularly tumour necrosis factor alpha (TNF-α) and interleukin (IL)-6 receptor inhibitors, suppress cytokine production, matrix metalloproteinase expression, osteoclastogenic signalling and FLS migration. Targeted synthetic DMARDs, particularly Janus kinase inhibitors (JAKis), exhibit broad activity across inflammatory, angiogenic, metabolic and tissue-destructive pathways. Despite their distinct molecular targets, all DMARD classes ultimately attenuate key pathogenic FLS functions associated with synovial inflammation and joint destruction. Conclusions: JAKis exert broad effects on RA-FLS function in vitro, likely reflecting their ability to block multiple cytokine-dependent signalling pathways. However, clinical evidence linking these effects to patient outcomes remains limited; further validation is therefore required. Full article

Background: Sports-related musculoskeletal injuries, including tendon, ligament, muscle, and cartilage damage, often heal slowly and incompletely. Current treatments may not fully restore tissue function, necessitating regenerative therapies. Objective: This study was conducted to review the therapeutic potential of stem cell-derived extracellular vesicles (EVs) and conditioned medium (CM) as cell-free approaches to treating musculoskeletal injuries in sports medicine. Methods: A narrative review of preclinical and early clinical studies investigating the biological mechanisms and regenerative effects of mesenchymal stem/stromal cell (MSC)-derived EVs and CMs published between 2019 and 2026 was performed by searching Scopus, PubMed, Web of Science, and Google scholar. Results: EVs and CMs contain bioactive molecules, including microRNAs, cytokines, and growth factors, that modulate inflammation, promote tissue repair, enhance angiogenesis, and support extracellular matrix remodeling. Preclinical studies demonstrate improved healing of tendons, ligaments, muscles, and cartilage, while early clinical evidence suggests favorable safety and promising therapeutic outcomes. However, the variety of MSC sources, EV separation methods, characterization procedures, and treatment protocols present major challenges in determining the reliability and therapeutic efficacy of these therapies. Notably, the number of clinical studies on EV and CMs is still limited, and most of the available studies are in vitro studies. Conclusions: MSC-derived EVs and CMs represent promising cell-free regenerative therapies for sports-related musculoskeletal injuries. The available evidence, which demonstrates their ability to enhance healing while avoiding the challenges associated with cell-based therapies, highlights their translational potential. However, most of the studies that are now available are preclinical or early-stage clinical studies, and there is still a limited number of clinical trials. Further well-designed clinical studies are needed to establish standardized protocols and confirm long-term safety. Full article

Background and Objectives: Osteoarthritis (OA) is the most common degenerative joint disease and a leading cause of pain and disability worldwide. Increasing evidence indicates that dysregulated iron metabolism contributes to joint degeneration by promoting inflammation, oxidative stress, and cartilage damage. Hemophilic arthropathy (HA), a severe complication of hemophilia caused by recurrent hemarthroses, represents a unique model of iron-driven joint degeneration. This narrative review summarizes current evidence on the contribution of iron deposition to the pathogenesis of hemophilic arthropathy and discusses its relevance to knee osteoarthritis (KOA). Materials and Methods: The literature was reviewed using the PubMed, Scopus, and Web of Science databases, focusing on published studies addressing iron deposition, synovial inflammation, angiogenesis, oxidative stress, cartilage degeneration, subchondral bone remodeling, and dysregulated iron metabolism. Results: Current evidence indicates that iron stored primarily as hemosiderin promotes persistent synovial inflammation and progressive joint destruction. Several pathological pathways associated with iron accumulation, including chronic low-grade inflammation, extracellular matrix degradation, and altered bone remodeling, are shared by HA and KOA. Conclusions: These findings suggest that iron-mediated mechanisms may provide important insights into OA pathogenesis and support further investigation of iron as a potential diagnostic and therapeutic target in degenerative joint diseases. Full article

Chronic synovial inflammation is a hallmark of osteoarthritis progression and is tightly regulated by synovial macrophages. Recently, voltage-gated sodium channels (NaV) have emerged as potent modulators of macrophage-driven inflammation, positioning them as novel therapeutic targets. Among selective NaV channel blockers, neosaxitoxin exerts remarkable anesthetic and immunomodulatory effects; however, its effects on joint inflammation upon intra-articular delivery remain unexplored. Using an equine model of bilateral carpal osteoarthritis, this study evaluated the immunomodulatory and tissue-preserving effects of intra-articular neosaxitoxin. Sixteen horses were randomized into two experimental groups (n = 8/each): Neosaxitoxin in one joint and triamcinolone (+control) in the contralateral joint; or neosaxitoxin in one joint and saline (−control) in the contralateral joint. Clinical parameters, synovial fluid cytology and cytokine profiles, and histological changes in synovium and cartilage were assessed over 30 days. Neosaxitoxin reduced synovial inflammation, evidenced by decreased synovial effusion and surface temperature, along with improved joint flexion. Furthermore, synovial fluid from neosaxitoxin-treated joints exhibited lower counts of erythrocytes, neutrophils, total protein, and key pro-inflammatory mediators (IL-1β and IL-6) compared to saline-treated controls. Histologically, neosaxitoxin-treated joints exhibited modest synovial inflammatory cell infiltration and minor cartilage abnormalities. In contrast, control joints exhibited synovial hyperplasia, fibrovascular proliferation, and cartilage degeneration. Our data suggests that intra-articular neosaxitoxin better preserved joint homeostasis by limiting synovial inflammation and cartilage damage. These results warrant further investigation on Neosaxitoxin as a candidate treatment for inflammatory arthropathies. Full article

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease defined by persistent synovial inflammation, progressive cartilage and bone erosion, and extra-articular manifestations. Current treatments, such as disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, and non-steroidal anti-inflammatory drugs (NSAIDs), control disease activity but are limited by toxicity, reduced response over time, and are expensive, demonstrating the need for safer and more effective adjuncts. The marine environment is a rich, largely untapped source of structurally diverse bioactive molecules that could be used to develop new therapeutics. This review compiles current evidence on anti-inflammatory and immunomodulatory compounds from marine organisms relevant to RA, including macroalgae, true marine microalgae, marine microorganisms (bacteria and fungi, including deep-sea taxa), sea cucumbers, sponges, mussels, corals, and jellyfish. Recurring mechanisms of action include inhibition of the NF-κB, MAPK, and JAK/STAT signalling cascades; suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2); reduced production of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6; and activation of the Nrf2 antioxidant response. Particular attention is given to functional lipids (eicosapentaenoic and docosahexaenoic acids, prostaglandin-like oxylipins) and pigments (astaxanthin, fucoxanthin, β-carotene) from marine microalgae and heterotrophic protists, which recent literature identifies as the most clinically advanced marine leads. To clarify translational status, compounds are grouped by their development stage (marketed nutraceutical, clinical trial, or preclinical) and summarised in a dedicated table. Some compounds, such as green-lipped mussel extract, microalgal omega-3 oils, and astaxanthin, have reached the stage of randomised controlled trials for arthritis. However, most other potential treatments are still in the early, preclinical phase. It is worth noting that ocean-derived compounds appear generally safe, but more thorough studies, especially in living organisms and in clinical settings, are needed to confirm their effectiveness for rheumatoid arthritis before any claims can be made about their therapeutic benefits. Full article

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by inflammation and cartilage destruction, partly mediated by interleukin (IL)-1β-induced nucle factor (NF)-κB activation. Ectoine (Ec) is a natural osmoprotectant with anti-inflammatory properties; however, its effects on NF-κB signaling in OA remain unclear. This study investigated whether ectoine attenuates IL-1β-induced inflammation in chondrocytes by suppressing NF-κB activation and mitigates OA progression in a rat model. Methods: Primary rat chondrocytes were pretreated with ectoine (0–3.0% w/v) and then stimulated with IL-1β (10 ng/mL). Cell viability was evaluated. RT-qPCR and Western blotting were used to determine the expression of inflammatory markers (inducible nitric oxide synthase [iNOS], cyclooxygenase [COX]-2, tumor necrosis factor [TNF]-α, and matrix metalloproteinase [MMP]-3/13), and NF-κB pathway activity was assessed through p65 phosphorylation and inhibitor of NF-κB alpha (IκBα) degradation. In vivo, OA was induced using the modified Hulth method, followed by intra-articular injection of ectoine alone or combined with hyaluronic acid (HA). Cartilage integrity was assessed using Osteoarthritis Research Society International (OARSI) scoring at 8 weeks. Results: Ectoine at 1.5% significantly inhibited IL-1β-induced NF-κB activation, reducing p65 phosphorylation by 59% and IκBα degradation by 41%. This inhibition decreased proinflammatory mediators (iNOS 43%, COX-2 35%, TNF-α 41%) and matrix-degrading enzymes (MMP-3 23%, MMP-13 31%), while increasing type II collagen by 84%. In vivo, ectoine reduced cartilage erosion (OARSI score: 7.0 vs. 10.2 in OA group). The Ec–HA combination improved cartilage retention by 43% compared with ectoine alone. Conclusions: These preclinical findings suggest that ectoine was associated with reduced NF-κB activation markers and attenuated OA-like changes in rat models. The enhanced effect observed with HA supports further investigation of combined therapeutic strategies for OA management. Full article

Introduction/Objectives: Temporomandibular joint osteoarthritis (TMJOA) causes pain, mandibular dysfunction, fibrocartilage degradation, and synovial inflammation. Current therapies are mainly palliative and limited by rapid intra-articular clearance and insufficient disease-modifying effects. This review summarizes injectable hydrogels for TMJOA as regenerative scaffolds, drug delivery systems, joint lubricants, and mechanical buffers. Methods: Relevant studies were identified from PubMed/MEDLINE, Web of Science and Google Scholar using terms related to TMJOA, injectable hydrogels, intra-articular delivery, tissue engineering, cartilage repair, lubrication, viscosupplementation and mechanical buffering. Studies were selected if they addressed hydrogel design, biological function, mechanical performance, biosafety or translational evaluation. Results: Injectable hydrogels have been investigated mainly as bioactive regenerative scaffolds and acellular functional biomaterials. Bioactive systems may regulate inflammation and oxidative stress, deliver cells, exosomes, drugs or growth factors, and support fibrocartilage repair. Acellular systems primarily aim to improve intra-articular retention, lubrication, viscoelastic adaptation and mechanical buffering. However, current evidence remains largely preclinical, with limited validation of long-term residence, degradation behavior, TMJ-specific mechanical performance, repeat dosing, biosafety and functional outcomes. Conclusions: Injectable hydrogels represent promising multifunctional platforms for TMJOA treatment. Cell-, exosome-, and growth factor-loaded systems show regenerative potential but face manufacturing, safety, regulatory, and long-term validation challenges. Acellular multifunctional hydrogels may be more feasible for near-term translation. Clinical Significance: Injectable hydrogels may provide minimally invasive, locally sustained treatment for TMJOA by integrating symptom control, microenvironment modulation, and mechanical adaptation. Full article

Background: Septic arthritis (SA) is a serious and rapidly progressive condition that can result in significant morbidity and mortality. Current clinical guidelines endorse a combination of surgical debridement and targeted antibiotic therapy as the gold standard treatment for adults with knee SA. Despite the effectiveness of this approach, patients often experience prolonged inflammation, leading to long-term complications such as cartilage degeneration and chronic pain. Since inflammatory cytokines contribute to cartilage destruction, it is considered to be possible that mitigating their levels through the use of steroids could potentially prevent cartilage damage. Methods: This study is designed as a multicenter, open-label, randomized controlled trial aimed at evaluating the efficacy of intravenous dexamethasone as an adjunctive therapy for adults diagnosed with knee joint SA. Participants aged 18 years and older will be randomized to receive either standard treatment (surgical debridement and antibiotics) or the same regimen with the addition of dexamethasone. The primary objective is to assess pain reduction at four days post-surgery using the EQ-VAS scale and knee joint effusion, while secondary objectives will include the evaluation of additional surgical interventions, pain control over time, joint function, normalization of inflammatory markers, and overall healthcare resource utilization. Discussion: While corticosteroids have demonstrated efficacy in pediatric populations with septic arthritis, the evidence for their use in adults remains limited. This trial aims to ascertain whether the anti-inflammatory effects of corticosteroids can mitigate complications and enhance clinical outcomes in adult patients with SA. The findings from this study could provide critical insights into optimizing treatment strategies for this complex condition, ultimately improving patient quality of life. Full article

Osteoarthritis (OA) is a significant clinical problem that places a substantial burden on both patients and the healthcare system. Characterized by progressive cartilage degeneration, synovial inflammation, and subchondral bone remodeling, OA is a rapidly growing and increasingly studied disease affecting millions around the world. Growing evidence has expanded on the traditional view of OA as a mechanical “wear-and-tear” disease, highlighting that disease progression is driven not only by mechanical stress but also by chronic dysregulation of the osteoimmune environment. Activation of innate and adaptive immune pathways, macrophage M1 polarization, and dysregulated cytokine signaling all contribute to progressive joint degeneration. While current therapeutics often focus on managing symptoms or restoring joint mechanics, interventions often overlook the role of osteoimmunology in disease progression. This review summarizes the biological and bioengineering strategies emerging to address OA. These platforms include bioceramics, metal-based scaffolds, hydrogels, nanoparticles, and microsphere systems. Furthermore, small molecules, cell-based therapies, and gene-modified systems have also been shown to modulate the inflammatory microenvironment, enhance regulatory immune responses, and restore cartilage homeostasis. Together, these approaches represent the evolving research landscape, shifting away from just symptom alleviation and towards targeted disease-modifying therapies, including osteoimmunomodulation. However, significant barriers to clinical translation remain, such as limited large animal studies and species immune system differences, which need to be addressed for the development of clinically applicable interventions. Full article