Objective To evaluate the safety and clinical performance of a high-purity, non–cross-linked 1.0% sodium hyaluronate administered via intra-articular injection in patients with symptomatic knee osteoarthritis (OA). Design This 30-week, single-center, open-label post-market clinical performance evaluation enrolled adults with radiographically confirmed knee OA. Participants received five weekly intra-articular injections of 1.0% sodium hyaluronate. Resting pain (VAS), Kellgren–Lawrence (KL) grade, and patient satisfaction were assessed through Week 30, and adverse events were monitored throughout. Results Mean VAS pain scores decreased by 48.3% at Week 8 and 42.8% at Week 30 compared with baseline (both p < 0.001). KL grades were generally stable over time, with no clear radiographic worsening observed during follow-up. Approximately 90% of patients reported satisfaction with treatment, and no treatment-related serious adverse events occurred. Conclusions Five weekly intra-articular injections of 1.0% sodium hyaluronate were well tolerated and were associated with reductions in resting pain and stable radiographic findings over 30 weeks, supporting its role as a well-tolerated viscosupplementation option in routine clinical care for knee OA.
Background Cell-based approaches for focal knee cartilage repair include cartilage- and chondrocyte-based procedures, mesenchymal stromal cell (MSC)-based strategies, and combinations of these approaches. However, the amount and type of evidence available for these treatments differ considerably. Objective To map the clinical and preclinical evidence for cell-based regenerative strategies used for focal chondral and osteochondral defects of the knee, compare cartilage-based, MSC-based, and hybrid approaches, and identify areas where evidence remains limited. Methods This scoping review was prospectively registered on the Open Science Framework and reported according to PRISMA-ScR. PubMed, Scopus, and Web of Science were searched for studies published from January 2000 to December 2025. Eligible studies evaluated in vivo cartilage-derived, MSC-based, or hybrid regenerative interventions for focal knee chondral or osteochondral defects. Two reviewers independently screened the records and charted study characteristics and outcomes using a standardized form. Because of substantial heterogeneity in interventions, study designs, models, outcomes, and follow-up periods, the findings were summarized descriptively rather than pooled. Results Seventy-five publications met the eligibility criteria. Cartilage-based approaches were evaluated in 29 publications, including 21 clinical and 8 preclinical studies. MSC-based approaches were evaluated in 43 publications, including 12 clinical and 31 preclinical studies. Three publications examined hybrid strategies, including two clinical reports from the same 35-patient cohort and one preclinical study. Cartilage-based evidence was therefore mainly clinical (72.4%), whereas MSC-based evidence was mainly preclinical (72.1%). Clinical studies used a wide range of outcome measures, and comparative studies did not show a consistent advantage of one more complex cell-based approach over another. Evidence for hybrid strategies remained limited to one preclinical study and one clinical programme reported at 18 months and 5 years. Conclusion The available evidence differs considerably across cartilage-based, MSC-based, and hybrid approaches. Cartilage-based techniques have been studied more extensively in clinical settings, whereas most MSC research remains preclinical. Hybrid cartilage and MSC strategies have been investigated in only a small number of studies. A framework based on structural or chondrogenic input, biological signaling, and the combination of these components may be useful for organizing future research, but it should currently be considered a hypothesis rather than a validated treatment model.
Background Post-traumatic osteoarthritis (PTOA) following intra-articular fractures (IAFs) remains a common sequela after injury. Cartilage degeneration after injury is influenced by multiple factors, including elevated proinflammatory cytokines produced by synovial fluid fracture hematoma (SFFH). Targeting this inflammatory response may reduce cartilage damage. This study evaluated cartilage injury and inflammatory mediator changes caused by SFFH, assessing whether commercially available anti-inflammatory agents can suppress the inflammatory cascade implicated in PTOA and reduce chondrocyte death. Methods Ankle synovial fluid was collected from 54 patients with IAFs. Human cartilage discs harvested from talar allografts were cultured in standard chondrocyte media (SCM) and initial media was collected. Explants were randomized into five groups: (1) control (SCM only), (2) sequential exposure SFFH representing acute (days 0–2), intermediate (days 3–9), and late (≥10) phases, (3) Group 2 with interleukin-1 receptor antagonist (IL-1Ra), (4) Group 2 with dexamethasone, and (5) Group 2 with doxycycline. After exposure, spent media was collected. Samples were analyzed for cytokines, matrix metalloproteinases (MMPs), C-terminal telopeptides of type II collagen (CTX-II), and sulfated glycosaminoglycans (sGAGs), with histological assessment performed to evaluate viability and proteoglycan content. Results SFFH exposed cartilage showed increased levels of proinflammatory cytokines, MMPs, and cartilage breakdown products compared to controls. Treatment with IL-1Ra, dexamethasone, or doxycycline all reduced inflammatory cytokines and MMP levels. Safranin O staining, indicating proteoglycan content, was lowest in group 2. No significant difference in chondrocyte survival was observed among groups. Conclusion Sequential exposure to SFFH creates a sustained proinflammatory and catabolic environment that promotes biochemical cartilage degradation. IL-1Ra, dexamethasone, and doxycycline reduced inflammatory cytokine and MMP concentrations while cartilage matrix degradation markers remained elevated and histologic preservation was not significantly improved. These findings suggest that suppression of inflammatory pathways alone may be insufficient to fully prevent cartilage injury under cumulative SFFH exposure. Clinical Relevance Acute anti-inflammatory therapy following IAF may modulate inflammatory and catabolic mediator production within the post-fracture joint environment. Further in vivo investigation is required to determine whether these biological effects translate into durable cartilage preservation or altered PTOA risk. Level of Evidence Laboratory study.
Objective Data evaluating knee flexion contracture (FC)-associated regional changes on femoral articular cartilage are lacking. We compared regional femoral articular cartilage outcomes of people with knee osteoarthritis (OA) with and without FC using quantitative MRI data. Methods Articular cartilage of the medial and lateral femoral condyles were segmented into internal, central, and external subregions on MRI. Goniometry measured knee extension. We tested for regional differences in cartilage thickness and percent denuded bone (i.e., 0mm cartilage thickness) in the presence or absence of FC, and for associations between cartilage outcomes with quantitative knee extension range of motion (ROM) using a linear model for 596 participants. Results For FC versus no FC, cartilage thickness in the central lateral subregion was higher (2.36±0.42mm vs. 2.29±0.43mm; p<0.05), with higher percent denuded bone in the central lateral (0.92±3.5% vs. 0.39±2.2%; p<0.05) and central medial subregions (4.61±12.88% vs. 3.17±11.66%; p<0.05). Lost knee extension was associated with increased percent denuded bone in the internal lateral ( r= 0.095; p<0.05), central lateral ( r =0.90; p<0.05), and central medial subregions ( r =0.117 ; p<0.01) but with increased central lateral cartilage thickness ( r =0.110; p<0.01). After correcting for clinical factors, an association between lost knee extension and increased percent denuded bone remained in the central lateral femur [ β =0.059; (95% CI 0.003–0.114)]. Conclusion Conclusion: Lost knee extension was associated with increased percent denuded bone in the central lateral and external medial femur. Interventions to maintain and/or restore knee ROM may benefit femoral cartilage health. Longitudinal studies evaluating the impact of lost knee ROM on femoral cartilage are warranted.
Background The aim of this study was to investigate the depth related spatial distribution of biochemical and structural components in articular cartilage at different topographical sites experiencing different loading within the juvenile equine metacarpophalangeal joint in two groups of foals subjected to different exercise conditions. Methods Sixteen Warmblood foals were included in the study and were randomly assigned into 1 of 2 exercise groups (box rest and box rest plus training) during the first 5 months of life and subsequently euthanized. Osteochondral plugs were harvested from two sites which have previously been shown to experience different load levels and sectioned into 100 μm thick slices. Cartilage slices were analysed for glycosaminoglycan, DNA, and total collagen content, as well as content of hydroxylysine residues (HYL) in collagen and the collagen cross-link Hydroxylysylpyridinoline (HP). Collagen fibril architecture (Orientation Angle and Parallelism Index) was determined using quantitative polarized light microscopy. Results The constantly loaded site 2 exhibited higher glycosaminoglycan (GAG) and HP content with HYL higher in the superficial and middle layers of the trained group, while the intermittently peak loaded site 1 showed greater collagen accumulation in deeper layers but lower cross-link density. Structural analyses (Oa and PI) confirmed that collagen fibril orientation and alignment adapt regionally, with training enhancing fibril organization in superficial zones. Conclusion This study illustrates that mechanical loading is a key driver of functional adaptation, resulting in distinct zonal and topographical differences in the biochemical and structural composition of equine cartilage at 5 months.
