Search Results (62)

Background: Knee osteoarthritis (KOA) is a degenerative joint disorder marked by cartilage degradation, synovial inflammation, and altered synovial fluid (SF) rheology, resulting in pain and impaired joint function. Intra-articular hyaluronic acid (IA-HA) injections aim to restore SF viscoelasticity and improve lubrication; however, their efficacy may be potentiated when combined with physiotherapy (PT). This monocentric observational study evaluated whether the addition of a multimodal PT program to IA-HA therapy enhances SF rheologic properties compared to IA-HA alone. Methods: A total of 52 patients (aged 47–61) with radiographically confirmed moderate KOA (Kellgren–Lawrence grade 2) were enrolled. Patients were assigned to a pilot group (PG; n = 37) receiving IA-HA (Kombihylan^®, 3 MDa) combined with a multimodal PT protocol, or a control group (CG; n = 15) receiving IA-HA alone. The PT program included ten sessions of transcutaneous electrical nerve stimulation, low-level laser therapy, therapeutic ultrasound, progressive exercise, and cryotherapy. SF samples were collected immediately after the first injection and again at six weeks, then analyzed rheologically using the Kinexus Pro+ rheometer. Viscosity parameters were assessed via steady and oscillatory shear tests. Results: At baseline, both groups demonstrated comparable SF viscosity profiles. After six weeks, the PG exhibited significantly higher shear viscosity values across all measured percentiles and reduced variability in rheological parameters, suggesting a more stable intra-articular milieu. Rheometric analysis indicated enhanced SF viscoelasticity, potentially mediated by reduced inflammation and stimulation of endogenous HA synthesis. In contrast, the CG showed inconsistent viscosity changes, reflecting variable responses to IA-HA monotherapy. Conclusions: Combining IA-HA with multimodal PT significantly improves SF rheological properties in moderate KOA patients compared to IA-HA alone. These findings support the role of mechanical stimulation in enhancing joint lubrication and homeostasis, offering a more consistent and effective approach to viscosupplementation. Full article

Intra-articular hyaluronan injections represent a widely used and generally safe therapeutic approach for knee osteoarthritis (OA). However, the side effects of this treatment remain insufficiently studied. Acute post-injection reactions, particularly those arising from an improper technique resulting in the deposition of the therapeutic agent into joint tissues, are well-documented. In contrast, chronic hyaluronan-induced inflammatory responses have received scant attention in the scientific literature. The aim of this study is to characterize for the first time the morphological patterns of chronic granulomatous inflammation induced by exogenous hyaluronan (e-HA) in osteoarthritic knees, focusing on three distinct tissue reactions: synovitis, adipositis, and osteomyelitis. Using a three-case series approach and morphological analysis, we identified e-HA penetration pathways; described associated foreign body responses in the synovial, adipose, and bone tissues of the joints; and emphasized the clinical relevance of these underreported adverse effects. These observations highlight an understudied phenomenon—an active conflict between e-HA and joint tissues that recognize it as a foreign body. The prevalence, clinical significance, and prognostic implications of this phenomenon require further investigation. Full article

Background/Objectives: Intra-articular injections of hyaluronic acid (HA) or platelet-rich plasma (PRP) have been used in the treatment of temporomandibular joint (TMJ) arthrocentesis to improve lubricative properties and influence regenerative processes. This study aimed to evaluate the potential clinical benefits of complementary bioviscosupplementation with hyaluronic acid (HA) and platelet-rich plasma (PRP) in patients undergoing double-portal TMJ arthrocentesis. Methods: A total of forty-six patients (33 females, 13 males; mean age of 45.83 ± 20.62 years) with arthrogenous temporomandibular disorders, identified through clinical and imaging examinations, were randomized into HA+PRP (23 patients) or HA-alone (23 patients) groups. The primary outcome variable was TMJ arthralgia; the secondary outcome was maximum mouth opening (MMO). All the outcome variables were assessed preoperatively (T0) and at several follow-ups (T1—1 month, T2—3 months, T3—6 months, T4—12 months follow-up). Results: The HA+PRP group presents lower TMJ arthralgia levels than the HA group at every follow-up moment (p < 0.05, r ≈ 0.3). At T3 and T4, the HA+PRP group presented a higher MMO average than the HA group (p = 0.03 and p = 0.02; r ≈ 0.3). At T4, the HA group’s success rate was lower than the HA+PRP group (65% vs. 96%), and a higher number of postoperative reinterventions were observed (35% vs. 4%). Conclusions: In this study, complementary intra-articular bioviscosupplementation (HA+PRP) following double-portal TMJ arthrocentesis was associated with better clinical outcomes regarding TMJ arthralgia reduction, MMO improvement, and reduced risk of future TMJ reintervention. Full article

Background/Objectives: Intra-articularly administered hyaluronic acid (HA) products improve the mechanical properties of the synovial fluid (SF) in an osteoarthritic (OA) joint and thus improve joint motion quality. However, current diagnostic methods, used to assess the clinical effectiveness of HA-based therapy are based on subjective tools, and are unable to deliver solid data about the actual impact of this molecule on joint functioning. Consequently, the aim of this study was to objectively assess the effect of HA IA injection on joint motion quality with vibroarthrography (VAG) and the subsequent evaluation of patient clinical status. Methods: A total of 40 patients with knee OA and 50 healthy individuals as the control group were enrolled in this non-randomized clinical and were subjected to therapy consisting of a single IA administration of highly concentrated HA gel (Biolevox™ HA ONE). The therapy assessment included an evaluation of joint motion quality with the VAG method and a subsequent evaluation of the knee joint function using the WOMAC questionnaire for up to 60 days after the therapy. Results: A single IA injection of HA led to an immediate and sustained improvement of the motion quality of OA-affected synovial joints, as proven by the significant reduction in all measured vibroacoustic emissions (VMS, R4, P1, and P2). Furthermore, this was followed by a significant improvement in all WOMAC sub-scales, observed at 30 and 60 days after the therapy. Conclusions: The results of this study demonstrate that an IA-HA injection can improve the motion quality of OA-affected joints. Importantly, the observed improvement in joint motion quality is directly correlated with early recovery of joint function. These findings provide objective evidence that HA effectively enhances OA-affected joint biomechanics, contributing to a better understanding of the actual impact of this prevalent OA therapy on knee joint motion quality. Full article

In a world where the incidence of non-specific lower back pain (LBP) is steadily increasing, researchers are still searching for effective solutions for patients. Hyaluronic acid (HA) viscosupplementation is commonly used to restore lubrication in osteoarthritis (OA) and other medical applications, but its rapid metabolism limits efficacy. This study evaluates whether an HA derivative can replace native HA for the treatment of non-specific LBP while maintaining or enhancing its frictional properties and improving in vivo stability. Six HA-based lubricants, both native and derivatized, were tested in a tribological rabbit fascia model and a new synthetic model. Reduced HA derivative showed better tribological properties and longer in vivo residence time compared to native HA, as demonstrated in pharmacokinetic studies in rabbits. The 316 kDa HA and reduced HA exhibited the most stable tribological properties, which were influenced by their molecular weight and concentration. These findings suggest that both native and reduced HA are promising viscosupplements for intrafascial injection in the treatment of LBP, with reduced HA potentially enhancing effectiveness through a prolonged effect. Full article

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage breakdown, synovial inflammation, and pain, which leads to significant disability. IAHA is widely used because of its viscoelastic properties, which restore synovial fluid homeostasis and reduce symptoms. However, emerging evidence suggests that IAHA exerts additional biological effects including chondroprotection, inflammatory modulation, oxidative stress reduction, and pain modulation, which may influence disease progression. Objective: This narrative review examines the biological mechanisms underlying IAHA’s role in OA management. The review explored IAHA’s effects on synovial fluid viscoelasticity, inflammatory cytokine modulation, cartilage preservation, oxidative stress regulation, and pain pathways, emphasizing the influence of molecular weight variations on therapeutic efficacy. Additionally, this review evaluates IAHA’s integration into multimodal treatment strategies, its potential disease-modifying effects, and future directions for personalized treatment approaches. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, EMBASE, Scopus, and Web of Science for studies published between January 2000 and March 2024. The search focused on IAHA’s molecular, cellular, and biochemical effects in OA and clinical findings assessing its impact on joint function, pain relief, and disease progression. Results: IAHA improves synovial fluid lubrication, reduces proinflammatory cytokines (IL-1β, TNF-α), inhibits matrix metalloproteinases (MMPs), scavenges reactive oxygen species (ROS), and modulates nociceptive pathways. High-molecular-weight IAHA demonstrates superior efficacy in advanced OA, while low-molecular-weight formulations may be better suited for early-stage disease. Although IAHA’s symptom relief is comparable to corticosteroids and NSAIDs, its favorable safety profile and emerging disease-modifying potential support its long-term use in OA management. Conclusions: IAHA represents a multifaceted therapeutic approach bridging symptomatic relief and regenerative strategies. While long-term efficacy, optimal administration protocols, and patient-specific responses remain subjects of ongoing research, refining treatment selection criteria, dosing regimens, and combination strategies may enhance clinical outcomes. Future studies should explore biomarker-driven approaches, standardize treatment protocols, and assess IAHA’s synergy with regenerative medicine to optimize its role in OA management. Full article

Synovial fluid (SF) plays a critical role in joint lubrication, load distribution, and maintaining homeostasis within the synovial cavity. Its rheological properties, primarily influenced by hyaluronic acid (HA) and other macromolecules, are essential for normal joint function. However, alterations in the physicochemical characteristics of SF can occur due to septic conditions, including septic arthritis (SA) and periprosthetic joint infections (PJIs), which significantly impact joint health. Bacterial colonization in infected joints often leads to the formation of biofilms, microbial aggregates encased in an extracellular matrix, which confer resistance to antibiotics and host immune responses. Biofilm formation in SF-altered environments is a major challenge in treating joint infections, particularly in patients with prosthetic implants. Viscosupplementation, primarily through intra-articular hyaluronic acid (HA) injections, has been widely used to restore SF viscosity and function in degenerative joint diseases. More recently, polyacrylamide (PAA)-based gels have emerged as an alternative viscosupplementation strategy. However, concerns have been raised regarding the potential impact of viscosupplements on biofilm formation and bacterial adhesion in septic joints, as changes in SF viscosity and composition may influence bacterial colonization and persistence. This review aims to assess the interaction between viscosupplementation and biofilm formation in septic joint pathologies, examining the effects of HA and PAA on SF rheology and bacterial adhesion. Understanding these interactions is crucial for optimizing therapeutic strategies and mitigating the risk of biofilm-associated infections in patients undergoing viscosupplementation. Full article

Objective: to evaluate the efficacy, safety, and cost-effectiveness of intra-articular hyaluronic acid (IAHA) in treating osteoarthritis (OA), considering innovations in formulations, comparative outcomes, and variability in guidelines. This review aims to synthesize evidence supporting the role of IAHA in multimodal treatment strategies. Materials and Methods: A general, narrative, umbrella review of systematic reviews and meta-analyses was conducted. Clinical practice recommendations and guidelines for IAHA use were also reviewed and evaluated. A comprehensive search was conducted across the main medical data sources. Inclusion criteria focused on studies evaluating the efficacy, safety, and impact of IAHA. Key outcomes included pain reduction (e.g., WOMAC, VAS), functional improvement, safety, and cost-effectiveness. Results: IAHA showed moderate efficacy in pain relief and functional improvement, especially in early-to-moderate OA. The results indicate that hybrid formulations and combination therapies show better clinical outcomes, with expanded efficacy and potential chondroprotection. However, heterogeneity between studies was noted, reflecting variability in patient populations and intervention protocols. International guidelines varied significantly, with some opposing routine use (e.g., AAOS, NICE) and others endorsing IAHA more or less conditionally (e.g., ESCEO, OARSI). Conclusions: IAHA remains a treatment modality in the arsenal of selected populations of people with OA, especially for early and moderate disease. High-quality, standardized studies are still needed to refine IAHA’s role and establish personalized guidelines for individual patients. A concerted effort to harmonize global recommendations and economic strategies, such as tiered pricing, can increase equitable access and optimize IAHA’s integration of multimodal treatment for OA. Full article

Post-traumatic osteoarthritis (PTOA) is a common cause of lameness in the horse. There is no cure, therefore treatments are aimed at reducing pain and improving the joint environment by modifying inflammatory pathways or by viscosupplementation. Here, we report the safety and efficacy of the biolubricant (poly(2-methacryloyloxyethyl phosphorylcholine; pMPC) to mitigate the physical, gross, histological, and biochemical effects of arthritis. We created an osteochondral fragment in the middle carpal joint of one limb in 16 horses to induce PTOA; the contralateral limb served as a sham-operated joint. Two weeks postoperative, half (n = 8) of the horses received a single injection of pMPC in the PTOA joint, while the other half received saline. All sham-operated joints (n = 16) received saline. We conducted clinical evaluations weekly while synovial fluid biomarkers were measured biweekly during the 70-day study period. Subsequently, we performed postmortem gross and histologic analyses. Horses in which PTOA joints were treated with pMPC exhibited mild increases in clinical data, including lameness, effusion, and flexion scores. Similarly, synovial cell count, total protein, and prostaglandin E₂ values were higher for pMPC-treated joints. Radiographic changes included significantly higher osteophyte scores in pMPC-treated joints at the terminal timepoint. The biolubricant may demonstrate some chondroprotective effects with lower total erosion scores and higher cartilage glycosaminoglycan content. In summary, when pMPC is administered to PTOA joints, the biolubricant induces a mild inflammatory response but may offer some chondroprotective effects in horses. Full article

Aims: Intra-articular (IA) injection therapy, particularly IA hyaluronic acid (HA), is a common treatment for knee osteoarthritis, but it does have limitations. The injection of IA polynucleotide (PN) has emerged as an alternative, potentially offering superior clinical outcomes. This study investigates current practice patterns and the perceived effectiveness of PN among clinicians for treating knee osteoarthritis in the Republic of Korea. Methods: Based on a survey conducted among clinicians who use PN in clinical practice, we explored the current practices and assessed the perceived effectiveness of IA PN in treating knee osteoarthritis. Results: A total of 265 clinicians who used IA PN for knee osteoarthritis participated in the survey. Most clinicians (73.3%) used PN therapy for the treatment of chronic pain, with varying administration frequencies. In addition, 25.8% of clinicians used PN for the treatment of acute flare-ups. In cases of knee effusion, 55.5% of clinicians removed the effusion prior to administering PN. Clinicians rated PN as more effective than HA for both chronic pain and acute flare-ups, with higher scores for cushioning, anti-inflammatory effects, and delaying joint degeneration. The clinicians stated that patients expressed a higher satisfaction with IA PN compared with IA HA, noting improvement in joint smoothness, noise reduction, pain relief, and a reduction in heat sensation and swelling. Conclusions: The results of the present study highlight the extensive use and perceived benefits among clinicians of IA PN for knee osteoarthritis in the Republic of Korea. Further research is warranted to explore the effectiveness of PN in acute flare-ups and to validate these findings in broader populations. Full article

Temporomandibular disorders (TMD) are a public health problem that affects around 12% of the global population. The treatment is based on analgesics, non-steroidal anti-inflammatory, corticosteroids, anticonvulsants, or arthrocentesis associated with hyaluronic acid-based viscosupplementation. However, the use of hyaluronic acid alone in viscosupplementation does not seem to be enough to regulate the intra-articular inflammatory process. So, we propose to develop and evaluate the physicochemical and biological properties in vitro of hyaluronic acid hydrogels (HA) associated with ketoprofen (KET) as a new therapeutic treatment for TMD. The hydrogels were synthesized with 3% HA and 0.125, 0.250, 0.500, or 1% KET. Physicochemical analyses of Attenuated Total reflectance-Fourier transform infrared spectroscopy (FTIR), Thermogravimetry (TGA), Rheology by Frequency, Amplitude sweeps, temperature ramp, and scanning electron microscopy (SEM) were performed with or without sterilization and cycled. Cytocompatibility and genotoxicity (micronucleus assay) were performed in mouse macrophages (RAW 264-7) for 24 h. Results: FTIR spectrum showed characteristic absorptions of HA and KET. In the TGA, two mass loss peaks were observed, the first representing the water evaporation at 30 and 100 °C, and the second peaks between 200 and 300 °C, indicating the degradation of HA and KET. Rheology tests in the oscillatory regime classified the hydrogels as non-Newtonian fluids, time-dependent, and thixotropic. Mouse macrophages (RAW 264-7) presented viability of 83.6% for HA, 50.7% for KET, and 92.4%, 66.1%, 65.3%, and 87.7% for hydrogels, in addition to the absence of genotoxicity. Conclusions: Hyaluronic acid associated with ketoprofen shows satisfactory physicochemical and biological properties for use as viscosupplementation. As a limiting point of this study, further research is needed to evaluate the pharmacodynamic, toxicological, and pharmacokinetic characteristics of a complete organism Full article

Background: Viscosupplementation consists of intraarticular hyaluronic acid injections applied to treat pain and improve joint mobility. The objective of the study was to analyze the improvement of the range of mobility of the first metatarsophalangeal joint with a single dose of cross-linked hyaluronic acid. Methods: Ten fresh frozen specimens of feet sectioned below the knee were selected. Before and after the infiltration procedure, the range of flexion was calculated for all specimen’s metatarsophalangeal joints. To detect complications due to the procedure, five feet were dissected and five were sectioned with a diamond saw. Results: The range of the first metatarsophalangeal joint flexion differences between the preoperative and the postoperative period was as follows: (1) 47° (range, 37–51.5) to 58° (range, 49–69.5) degrees of loaded dorsiflexion (p > 0.006); (2) 41° (range, 40–51.5) to 58° (range, 52.5–66.5) degrees of unloaded dorsiflexion (p > 0.009); and (3) 14° (range, 10.5–24.25) to 16° (range, 14.25–28.5) degrees of unloaded plantarflexion (p > 0.083). No injuries of anatomical structures were observed either by anatomical dissection or in the anatomical sections. Conclusions: The results obtained in this viscosupplementation study demonstrate the improvement of the range of mobility of the first metatarsophalangeal joint without evidence of extravasation and lesions of the periarticular anatomical structures. Full article

Background/Objectives: Osteoarthritis (OA) is the most common joint disease in the adult population. OA is the result of multiple mechanisms leading to inflammation and the degradation of the cartilage. A complex series of etiological actors have been identified so far, including extracellular vesicles (EVs). The EV content of the synovial fluid (SF) can release inflammatory mediators that enhance OA progression. An intra-articular viscosupplementation of high-MW hyaluronic acid (HyA) constitutes the first-line conservative treatment for OA. Although attractive for the potential pharmacological implications, the possibility that HyA may interact with EVs in the context of OA has not yet been specifically investigated; therefore, the present study aimed to fill this gap. Methods: We studied the effect of a HyA preparation (a blend of crosslinked and linear polymers, CLHyA) on the relevant inflammatory markers in chondrocytes (HC cells or primary chondrocytes isolated from patients with advanced OA) exposed to the EVs collected from IL-1β-stimulated THP-1 human monocytes (EVs+). Results: EVs+ caused specific inflammatory responses in chondrocytes that could be prevented by coincubation with CLHyA. This anti-inflammatory activity is likely dependent on the direct binding of CLHyA to CD44 receptors highly expressed in EVs+ and on the subsequent hindrance to EVs+ diffusion and docking to target cells. Conclusions: On the whole, the tight interactions identified herein between HMW HyA and EVs+ represent a novel, pharmacologically exploitable mechanism potentially relevant in the context of OA treatment. Full article

Background/Objectives: osteoarthritis (OA) is a leading cause of disability. With an aging population and rising obesity rates, OA presents a growing challenge to health systems worldwide. Current OA treatments involve a mix of pharmacological and nonpharmacological interventions. Viscosupplementation with hyaluronic acid (HA) has proven effective, especially in knee OA, leading to its recommendation in international guidelines. This study investigates the sustained benefits of a single intra-articular HA injection beyond one year in patients coming from the SOYA trial, considering the EU MDR 2017/745 emphasis on post-market follow-up. Methods: A prospective, observational, open, post-marketing study in a cohort of patients that participated in the SOYA trial. Follow-up was carried out by means of a telephone survey, and the data were anonymized and coded so that patients could not be identified. The study was approved by the Alcorcón Hospital Institutional Review Board (Alcorcón, Madrid, Spain). Results: In the follow-up of the SOYA trial, 81.5% of patients sustained positive effects for over 6 months after the trial ended. This correlated with improved daily functioning, enhanced mood, and high patient satisfaction. Younger age and milder OA grades were associated with prolonged treatment effects. Notably, 82% of patients with >6 months of improvement did not require additional medication. Conclusions: the results of this study support the safety and performance of Adant^® Plus as a treatment for patients with mild and moderate knee OA, with results lasting more than one year. Post-marketing studies are particularly relevant to examine the experience gained with the use of the device in routine clinical practice. Full article

Background/Objectives: There is a gap between the very positive opinion of patients and doctors regarding knee viscosupplementation (VS) and the contrasting results of controlled studies. The objective of this study was to evaluate the overall satisfaction and predictors of satisfaction with VS in patients with knee osteoarthritis treated with VS. Methods: Post-hoc analysis of a cross-sectional study in patients with knee OA treated with one injection of a mannitol-modified cross-linked HA (HANOX-M-XL). The primary outcome was satisfaction, self-assessed semi-quantitatively by the patients. Demographics, radiological features, comorbidities, OA and comorbidities treatments, and lifestyle associated with satisfaction were studied in bivariate and multivariate analysis. Results: 89 patients (124 knees) were analyzed. A total of 88.7% were satisfied with the treatment. Satisfaction was correlated with duration of effectiveness (DoE) and negatively correlated with BMI. Satisfaction was higher in active versus sedentary patients, in tibiofemoral involvement, in Kellgren-Lawrence grade 1–3 versus 4, and in subjects not requiring intraarticular corticosteroid (IACS) concomitantly to VS. Satisfied subjects were older than dissatisfied ones. In multivariate analysis, older age, K–L grade < 4, absence of IACS, and longer DoE were associated with higher rates of satisfaction. Conclusions: We identified several predictive factors of patient satisfaction after VS of the knee. Alongside these objective factors, there are probably subjective factors linked to patient beliefs, fears, and expectations impacting satisfaction. Full article