Application of magnetic particle imaging to evaluate nanoparticle fate in rodent joints.

Nanoparticles are a promising approach for improving intra-articular drug delivery and tissue targeting. However, techniques to non-invasively track and quantify their concentration in vivo are limited, resulting in an inadequate understanding of their retention, clearance, and biodistribution in the joint. Currently, fluorescence imaging is often used to track nanoparticle fate in animal models; however, this approach has limitations that impede long-term quantitative assessment of nanoparticles over time. The goal of this work was to evaluate an emerging imaging modality, magnetic particle imaging (MPI), for intra-articular tracking of nanoparticles. MPI provides 3D visualization and depth-independent quantification of superparamagnetic iron oxide nanoparticle (SPION) tracers. Here, we developed and characterized a polymer-based magnetic nanoparticle system incorporated with SPION tracers and cartilage targeting properties. MPI was then used to longitudinally assess nanoparticle fate after intra-articular injection. Magnetic nanoparticles were injected into the joints of healthy mice, and evaluated for nanoparticle retention, biodistribution, and clearance over 6 weeks using MPI. In parallel, the fate of fluorescently tagged nanoparticles was tracked using in vivo fluorescence imaging. The study was concluded at day 42, and MPI and fluorescence imaging demonstrated different profiles in nanoparticle retention and clearance from the joint. MPI signal was persistent over the study duration, suggesting NP retention of at least 42 days, much longer than the 14 days observed based on fluorescence signal. These data suggest that the type of tracer - SPIONs or fluorophores - and modality of imaging can affect interpretation of nanoparticle fate in the joint. Given that understanding particle fate over time is paramount for attaining insights about therapeutic profiles in vivo, our data suggest MPI may yield a quantitative and robust method to non-invasively track nanoparticles following intra-articular injection on an extended timeline.

Can radiological findings detect neuropathic pain in patients with osteoarthritis of the knee undergoing surgery?

OBJECTIVES: The mechanism underlying neuropathic pain (NP) in osteoarthritis (OA) of the knee is not completely understood. This study aimed to investigate whether possible NP in patients with knee OA undergoing knee surgery is associated with specific radiological findings. METHODS: This study included 197 patients who underwent knee surgery for symptomatic knee OA. Clinical evaluation was performed using the Central Sensitization Inventory (CSI), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and PainDETECT questionnaire. Radiological evaluation was performed using the hip-knee-ankle (HKA) angle, posterior tibial slope (PTS), varus and valgus laxities, and magnetic resonance imaging OA Knee Score (MOAKS). Radiological findings were compared between patients with possible and unlikely NP. Logistic regression analysis was performed to identify the predictive factors for NP. RESULTS: There were 163 and 34 patients with unlikely NP and with possible NP, respectively. The percentage of patients with CSI score ≥ 40 was significantly higher in the possible NP group than in the unlikely NP group (17.6% vs. 6.1%). Patients with possible NP had worse WOMAC scores than patients with unlikely NP. There were no significant positive associations between the possible NP and radiological findings in knee OA. Regression analysis showed no predictive factors for possible NP. CONCLUSIONS: Possible NP is not associated with specific radiological findings in knee OA. Patients with possible NP may mediate CS and experience more severe symptoms, including decreased knee function and lower quality of life, than patients with unlikely NP.

Comparison of Clinical and Imaging Outcomes of Different Doses of Adipose-Derived Stromal Vascular Fraction Cell Treatment for Knee Osteoarthritis.

Favorable clinical outcomes of intra-articular injection of adipose-derived stromal vascular fraction (SVF) cells for knee osteoarthritis (OA) have been reported, but the effects of different doses of SVF cells have not been examined. This study aimed to compare the short-term clinical and imaging outcomes of different doses of SVF cells for knee OA treatment. This study included 60 patients with knee OA who underwent intra-articular injection of SVF cells. The follow-up period was at least 12 months. Thirty patients received an intra-articular injection of 2.5×107 SVF cells (low-dose group), and the remaining 30 patients received an intra-articular injection of 5.0×107 SVF cells (high-dose group). Clinical evaluations were performed for the Knee injury and Osteoarthritis Outcome Score (KOOS). Imaging evaluations, including the magnetic resonance imaging Osteoarthritis Knee Score (MOAKS) features (bone marrow lesions, cartilage defects, osteophytes, Hoffa's synovitis, and effusion synovitis), were also performed. All clinical and imaging evaluations were performed preoperatively and 12 months postoperatively and compared between the groups. In demographic data, no significant differences were found between the two groups. The total score of KOOS at 12 months postoperatively was significantly more favorable than the preoperative score in the high-dose groups. Pain and symptoms subscale scores of KOOS at 12 months postoperatively were significantly better in the high-dose group than in the low-dose group. The bone marrow lesions, Hoffa's synovitis, and effusion synovitis improved approximately 30-40% at 12 months postoperatively compared to baseline in both groups. However, there were no significant differences in imaging evaluations between the two groups. In conclusion, the pain and symptoms subscale scores of KOOS from baseline to 12 months postoperatively improved better in the high-dose group than in the low-dose group. Our findings suggest that intra-articular injection of SVF cells for knee OA is an innovative approach.

Clinical outcomes following injections of leukocyte-rich platelet-rich plasma in osteoarthritis patients.

BACKGROUND: Scientists are trying to discover how to repair cartilage defects in knee osteoarthritis (KOA). In our previous study, we found a fibrocartilage-rich cover over the defective portions of cartilage after administering leukocyte-rich platelet-rich plasma (LR-PRP). This study aimed to investigate the efficacy of multiple injections of LR-PRP for the treatment of KOA and determine an LR-PRP treatment protocol for KOA in actual clinical practice. HYPOTHESIS: We hypothesized that using abundant LR-PRP would improve outcomes in patients with KOA. STUDY DESIGN: Prospective, cross-sectional, interventional, randomized trial. METHODS: Intra-articular LR-PRP injections were administered to 50 knees. Patients received six injections of LR-PRP in total, which were administered at 4-week intervals. Patients were evaluated based on clinical outcomes, including visual analog scale (VAS) scores, Knee injury and Osteoarthritis Outcome Scores (KOOS), and magnetic resonance images (MRI) and radiographic findings before treatment and at 3 and 6 months after treatment. We investigated the recurrence of pain and presence/absence of MRI changes. Furthermore, we examined the Outcome Measures In Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria. RESULTS: The mean improvement rate, as assessed by VAS, was 61.6% (P < .0001). Concerning OMERACT-OARSI, 37 of 50 knees (74%) were considered responders. There was a significant difference in the follow-up MRI findings, as assessed by the MRI Osteoarthritis Knee Score for bone marrow lesions (P < .007). No significant difference in osteoarthritis grade was observed. CONCLUSION: Our LR-PRP procedure resulted in 74% of knees being classified as responders, regardless of the degree of knee deformation. Multiple injections of LR-PRP was effective for advanced grades of KOA. Thus, based on the results of our study, we believe that LR-PRP should be implemented as an additional conservative treatment option for non-operative management of OA. TRIAL REGISTRATION: Japan Medical Association Center for Clinical Trials (JMA-XXX).

Dolor en la artrosis de rodilla / Pain in knee osteoarthritis

El dolor constituye el síntoma fundamental de la artrosis, sus características e interpretación permiten el diagnóstico certero y también conocer la magnitud de esa entidad. El objetivo de este trabajo, es profundizar los conocimientos sobre los elementos más esenciales relacionados con el dolor en la artrosis de la rodilla. Se describen las causas mecánicas y bioquímicas del dolor, entre las que resaltan el dolor óseo, sinovial, así como los factores bioquímicos relacionados con ese síntoma. Se hace referencia a las principales estructuras anatómicas responsables del dolor y sus mecanismos de acción. Se mencionan la relación existente entre ese síntoma y las modalidades imagenológicas, así como los patrones del dolor. Para finalizar, se hace referencia a las escalas de dolor usadas.

Pain is the main symptom of osteoarthritis. Determining the distinctive features of pain in knee osteoarthritis allows for an accurate diagnosis. This article gives a review of the results from research work on the typical features of knee osteoarthritic pain. The mechanics and biochemical causes of pain are described including both bone and synovial biochemical symptom-related factors. The relationships between knee pain, various imaging techniques and pain mechanism are also identified. Finally, the used pain scales are presented.