Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy.

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

Clinical efficacy of multiple intra-articular injection for hip osteoarthritis.

Aims: Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods: This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results: In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion: Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes.

[Therapy of degenerative changes in the ankle joint with US-guided linear hyaluronic acid injections. A review].

The article discusses the issue and our own experience of local therapy for osteoarthritis of the ankle joint with injections of linear hyaluronic acid under ultrasound navigation. Since the ankle joint is difficult in terms of surgical treatment in general and endoprosthetics in particular, a course of intra-articular injection of 1% Flexotron® Forte hyaluronate, especially in the early stages of dystrophic changes in cartilage, is a promising method for relieving pain, chondroprotection and preserving the biomechanics of the joint, and ultrasound navigation when performing manipulation, it ensures the most accurate introduction of the drug into the joint cavity.

The effect of sodium hyaluronate on dry eye and corneal epithelial thickness following cataract surgery.

PURPOSE: To evaluate the effects of sodium hyaluronate drops on dry eye parameters and corneal epithelial thickness following cataract surgery. METHODS: The study included 84 patients who underwent uncomplicated phacoemulsification. In Group A, 0.15% sodium hyaluronate drops were added to the postoperative antibiotic/anti-inflammatory treatment. In Group B, only antibiotic/anti-inflammatory treatment was applied. Preoperatively and at 1 week and 1 month postoperatively, all the patients were evaluated in respect of tear break-up time (TBUT), the Schirmer test under anesthesia, the corneal fluorescein staining (CFS) score, mean central corneal thickness (CCT) and mean central corneal epithelial thickness (CCET), and the two groups were compared. RESULTS: A statistically significant difference was determined between the two groups at postoperative 1 month in respect of TBUT, Schirmer test, CFS score, and CCET (p < 0.01). In Group A, a statistically significant increase was determined in the TBUT and Schirmer values at 1 month postoperatively (p < 0.01, p = 0.01, respectively) and in Group B, these values were decreased compared to preoperatively (p < 0.01). The CCET was determined to be significantly thinner in Group B 1 month postoperatively (p < 0.01). A significant increase in CCT was observed in both groups at postoperative 1 week (p < 0.01) and preoperative values were reached at 1 month postoperatively. CONCLUSION: In the patient group using sodium hyaluronate, significant differences were determined in all dry eye parameters and CCET. The use of hyaluronate sodium drops after cataract surgery was seen to improve dry eye parameters and contribute to a healthy ocular surface by ensuring continuity of the corneal epithelium.

Viscosupplementation with High Molecular Weight Hyaluronic Acid for Hip Osteoarthritis: a Systematic Review and Meta-Analysis of Randomised Control Trials of the Efficacy on Pain, Functional Disability, and the Occurrence of Adverse Events.

PURPOSE OF THE STUDY: Hip osteoarthritis (OA) has a prevalence of around 6.4% and is the second most commonly affected joint. This review aims to assess the clinical outcomes of intra-articular high molecular weight hyaluronic acid (HMWHA) in the management of hip osteoarthritis. MATERIAL AND METHODS: We conducted a comprehensive search across PubMed, Google Scholar, and the Cochrane Library for randomised trials investigating the effectiveness of high molecular weight hyaluronic acid (HMWHA) in the treatment of hip osteoarthritis. Quality and risk of bias assessments were performed using the Cochrane RoB2 tool. To synthesise the data, we utilised the Standardised Mean Difference (SMD) for assessing pain relief through the Visual Analogue Scale (VAS) and the Lequesne index (LI) for evaluating functional outcomes. Risk Ratio (RR) was calculated to assess the occurrence of complications. RESULTS: A total of four studies involving HMWHA and control groups were included. The standardised mean difference (SMD) for the Visual Analogue Scale (VAS) (SMD -0.056; 95% CI; -0.351, 0.239; p = 0.709) and the Lequesne index (SMD -0.114; 95% CI; -0.524, 0.296; p = 0.585) were not statistically significant. Analysis for complications demonstrated an overall relative risk ratio (RR) of 0.879 (95% CI; 0.527, 1.466; p = 0.622), and was not statistically significant. DISCUSSION AND CONCLUSIONS: Intra-articular HMWHA in hip OA can significantly reduce pain and improve functional recovery when compared with the condition before treatment. However, there is no significant difference between HMWHA, or saline, or other therapeutic treatments. Currently, available evidence indicates that intra-articular HMWHA in hip OA would not increase the risk of adverse events. KEY WORDS: hip osteoarthritis, hyaluronic acid, intra-articular, molecular weight, viscosupplementation.

Air bubble guide for adequacy of ophthalmic viscosurgical device during phacoemulsification.

Phacoemulsification in hard cataracts is a challenge. The use of dispersive ophthalmic viscosurgical devices (OVDs) to protect the endothelium is a routine step in such scenarios. However, as OVD is transparent, it is difficult to spot within the anterior chamber. Therefore, surgeons may not be aware when the OVD coating of the endothelium disappears during surgery. Consequently, there may be too frequent OVD injections, resulting in a waste of resources. On the contrary, the surgeon may fail to inject OVD at an appropriate time, leading to greater endothelial damage. We propose a novel technique of using an air bubble as a guide that helps in identifying the time when OVD disappears from the anterior chamber, thereby suggesting the surgeon to reinject before proceeding further.

A Low Transition Temperature Mixture-based viscosupplementation complemented with celecoxib for osteoarthritis treatment.

Viscosupplementation consists of hyaluronic acid (HA) intra-articular injections, commonly applied for osteoarthritis treatment while non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered for pain relief. Here, HA and a NSAID (celecoxib) were combined in a formulation based on a low transition temperature mixture (LTTM) of glycerol:sorbitol, reported to increase celecoxib's solubility, thus rendering a potential alternative viscosupplement envisioning enhanced therapeutic efficiency. The inclusion of glucosamine, a cartilage precursor, was also studied. The developed formulations were assessed in terms of rheological properties, crucial for viscosupplementation: the parameters of crossover frequency, storage (G') and loss (G'') moduli, zero-shear-rate viscosity, stable viscosity across temperatures, and shear thinning behaviour, support viscoelastic properties suitable for viscosupplementation. Additionally, the gels biocompatibility was confirmed in chondrogenic cells (ATDC5). Regarding drug release studies, high and low clearance scenarios demonstrated an increased celecoxib (CEX) release from the gel (6 to 73-fold), compared to dissolution in PBS. The low clearance setup presented the highest and most sustained CEX release, highlighting the importance of the gel structure in CEX delivery. NMR stability studies over time demonstrated the LTTM+HA+CEX (GHA+CEX) gel as viable candidate for further in vivo evaluation. In sum, the features of GHA+CEX support its potential use as alternative viscosupplement.

Tear film stability in patients with symptoms of dry eye after instillation of dual polymer hydroxypropyl guar/sodium hyaluronate vs single polymer sodium hyaluronate.

PURPOSE: This study evaluated the tear film stability in patients with symptoms of dry eye after installation of dual polymer hydroxypropyl guar/sodium hyaluronate (DPHG/SH) vs single polymer SH. METHODS: Patients with recently diagnosed mild to moderate dry eye disease (OSDI score 23-32 points) were included. For each patient, the right eye was randomized to receive DPHG/SH or 0.15% SH. Just after the administration of the drop to the right eye, the fellow eye received the other eye drop. The first non-invasive Keratograph first break-up time (NIKBUT), average NIKBUT and tear meniscus height (TMH) were measured before administration of the eye drops, at 1-min, 15 min, 30 min, 60 min, 90 min, and 120 min after instillation. RESULTS: A total of 29 patients aged 22.8 ± 2.2 years participated in the study (21 women). No differences between the eye receiving DPHG/SH and single polymer SH were observed for the first NIKBUT (p = 0.45) and average NIKBUT (p = 0.24) variables at any time point. Both DPHG/SH and single polymer SH increased the TMH (p of time effect < 0.001), but with no difference between groups (p = 0.95). CONCLUSION: Both DPHG/SH and single polymer SH solutions provide lubrication of the eye surface, however, with no difference in NIKBUT and TMH evaluations for up to two hours following administration.

Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score. METHOD: Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies-of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines. RESULT: Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001). CONCLUSIONS: Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.

Gait kinematics of osteoarthritic knees after intra-articular viscosupplementation: A double-blinded randomized controlled trial.

BACKGROUND: The utilization of subjective questionnaires for assessing conservative treatment in knee osteoarthritis may present challenges in identifying differences due to inadequate statistical power. Objective tools, such as three-dimensional (3D) kinematic analysis, are accurate and reproducible methods. However, no high-quality studies assessing the effects of intra-articular viscosupplementation (VS) have been published. Therefore, the objective of the study was to evaluate gait kinematics of patients with advanced knee osteoarthritis after VS. METHODS: Forty-two patients were randomized to receive either VS or saline injection (placebo). They underwent 3D kinematic gait analysis before and at 1, 6, and 12 weeks after treatment and knee angles during stance phase were determined. Patients and the healthcare team responsible for data collection, processing, and analysis were blinded to group allocation. Between-group comparisons were conducted using linear mixed models. RESULTS: Compared with placebo, the VS increased the maximum knee extension (3.2° (0.7-5.7)) and decreased the maximum knee flexion (-3.6° (-6.1 to -1.2)) on the sagittal plane at 1 week. At 6 weeks, the VS group sustained a reduced maximum knee flexion (-2.6° (-5.2 to 0.0)). On the axial plane, the VS group demonstrated an increase in maximum internal rotation at 12 weeks (3.9° (0.3 to 7.7)). The VS group exhibited reduced single-leg stance time at 1 week and increased total stance time at 12 weeks. CONCLUSIONS: VS led to short- and long-term kinematic improvements in the sagittal and axial planes, leading to a gait pattern closer to that observed in individuals with less severe osteoarthritic knees.

Platelet-Rich Plasma, Bone Marrow Aspirate Concentrate, and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months. METHODS: A literature search was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews. Level I to II randomized clinical trials with a minimum follow-up of 6 months that investigated the treatments of interest were included. Patient-reported outcome scores for pain and function at baseline and at latest follow-up were extracted, and the change in scores was converted to uniform 0 to 100 scales. Arm-based Bayesian network meta-analysis using a random-effects model was created to compare the treatment arms in pain and function. RESULTS: Forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was HA (40.9%), followed by placebo (26.2%), PRP (21.5%), CS (8.8%), and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared with placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo. Surface under the cumulative ranking curves (SUCRAs) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function, with overall SUCRA scores of 91.54, 76.46, and 53.12, respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70, respectively. CONCLUSIONS: At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared with BMAC, HA, and CS. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I to II studies.

Evaluation of single and multiple hyaluronic acid injections at different concentrations with high molecular weight in the treatment of knee osteoarthritis.

BACKGROUND: Knee osteoarthritis is severe progressive and most commonly diagnosed articular disease and its incidence is increasing around the world depending on age. This pathologic condition which limits daily activity of patients can be characterized by degeneration of cartilage and inflammation. Although non-steroidal anti-inflammatory (NSAII) agents and other analgesics are routinely used treatment options, the potential effects of intraarticular injections including hyaluronic acid (HA) have also been demonstrated by various studies. However, few studies compare the efficacy of a single high molecular weight (HMW) high dose and a triple HMW low dose. This study aimed to compare the efficacy of single high molecular weight (HMW) high dose (2 mL / 60 mg) and triple HMW low dose (2 mL /30 mg) intra-articular injection of HA in knee osteoarthritis (OA) patients by evaluating function and pain parameters during 12 months. METHODS: This is a single-center, retrospective clinical study that included and involved 128 patients. Group I (n=64) patients received triple 30 mg HA injections (SEMICAL®) with one-week intervals, while Group II (n=64) patients received a single 60 mg HA injection (SEMICAL®). Lequesne Index, WOMAC and VAS scores were recorded to assess pain and function during a 12-month period. RESULTS: There was no significant difference in characteristics of patient demographics. Our finding indicate that WOMAC, VAS score, and Lequesne Index values during follow-up visits exhibited a decrease, signifying improvement in the clinical condition. Notably, scores were significantly more favorable with the 30 mg of HA injection compared to the 60 mg of HA injection. CONCLUSION: This study suggests that the triple low-dose injection of HMW HA is more effective in improving WOMAC, VAS scores and Lequesne Index values than a single high-dose injection.

Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

OBJECTIVE: This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery. METHODS: The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses. RESULTS: Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I2=48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I2=0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation. CONCLUSION: Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes.

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

BACKGROUND: There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. OBJECTIVE: The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. METHODS: For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. RESULTS: The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. CONCLUSION: A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Application frequency - key indicator for the efficiency of severe dry eye disease treatment - evidence for the importance of molecular weight of hyaluronan in lubricating agents.

PURPOSE: Lubricant eye drops are the main therapeutic resource for dry eye disease (DED), with each drop representing the equivalent of ocular surface disease treatment. Thus, any reduction in the frequency of eye drop application reflects a degree of therapeutic success. Considering also the socioeconomic burden of DED, we investigated eye drop application frequency (DF) as a parameter to potentially track the success of therapy in severe DED. Hyaluronan (HA)-containing eye drops have become the first choice for tear substitution in many countries, and recent data indicate that the average molecular weight (Mw) of HA determines the therapeutic efficacy of such eye drops. This post-hoc subgroup analysis of a previously published multicentre prospective randomized open-label study, HYLAN M, is set out to compare the effects of very high Mw HA (hylan A) eye drops to comparator eye drops, containing lower Mw HA (control). METHODS: Patients with severe DED (n = 47), recruited as part of the larger HYLAN M prospective, multicentre, open-label study, were randomized into two groups: hylan A and control group. In the hylan A group, 24 patients replaced their HA-containing eye drops with eye drops containing 0.15% hylan A, whereas the 23 control patients continued to use comparator HA eye drops. The DF was recorded daily by all participants over 8 weeks, and other subjective and objective parameters of DED were assessed at the time of inclusion (baseline), as well as at week 4 and 8. RESULTS: There was a significant decrease in DF in the hylan A users between the baseline and week 4 (p = 0.004), remaining stable until week 8. Indeed, in contrast to the baseline, the hylan A group had a significantly lower DF than the control group at weeks 4 (p = 0.018) and 8 (p = 0.008). Likewise, the ocular surface disease index (OSDI) improved significantly between the time of inclusion and week 4 (p < 0.001) in hylan A users, remaining stable until week 8. The OSDI was similar in both groups at the baseline but it was significantly lower in the hylan A group than in the control group at week 4 (p = 0.002), remaining lower at week 8. Such a decrease in the DF and OSDI was not witnessed in the control group at any time point. The objective parameters assessed did not differ significantly within or between the two groups. CONCLUSION: When treating severe DED, the DF can be significantly reduced by using very high Mw HA (3 MDa) lubricant eye drops, which better alleviate DED symptoms and decrease the OSDI scores. These drops not only provide an attractive and comfortable alternative for patients with severe DED but also offer the possibility of reducing the disease's socioeconomic burden, both for affected individuals and society as a whole.

Different doses of hyaluronic acid injections in patients with knee osteoarthritis: A multicenter, randomized, prospective, single-blind, clinical study.

BACKGROUND: Many formulations and dosing regimens are available for hyaluronic acid (HA). OBJECTIVE: To compare different doses of linear, high-molecular weight (HMW) HA injections among patients with knee osteoarthritis (OA). METHODS: Hundred patients were included in this randomized, single-blinded trial and randomly divided into three HA injection groups. The first group received five weekly 20 mg HA injections, the second group received three weekly 32 mg HA injections, and the third group received a single 48 mg HA injection. Patients were evaluated at baseline, 1, 3, and 6 months after the last injection for pain, stiffness, and function using the visual analog scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Quality of life, patient's global assessment, and Timed Up and Go (TUG) test scores were also evaluated. RESULTS: There was significant improvement in the WOMAC, VAS-pain, quality of life, patient's global assessment, and TUG test mean scores at all follow-up time points (p< 0.001). However, the groups showed no significant differences in WOMAC, VAS-activity pain, and patient global scores at any follow-up point. CONCLUSION: Intra-articular injections of different doses of linear HMW HA can improve pain, stiffness, function, and quality of life in patients suffering from knee OA over a six-month period.

Intra-articular Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review of Product Properties.

INTRODUCTION: There are many intra-articular hyaluronic acid (IA-HA) products on the market that have known intrinsic differences in molecular size, source, and structure. The current review summarizes existing evidence describing and assessing these differences, while also identifying whether these differences have an impact on clinical outcomes. METHODS: This systematic review summarized all literature that specifically addresses IA-HA product differences. Included studies summarized basic science and mechanism of action comparisons of IA-HA product differences, or systematic reviews that assess differences in clinical outcomes between IA-HA product differences. RESULTS: A total of 20 investigations assessed basic science differences between IA-HA products, while 20 investigations provided assessments of the clinical outcome differences between IA-HA product characteristics. The published basic science literature provided a differentiation between low molecular weight (LMW) and high molecular weight (HMW) HA with regard to changes within the synovial fluid, driven by the interactions that these molecules have with receptors in the joint space. These differences in receptor interaction manifest within clinical outcomes, as meta-analyses comparing pain relief after IA-HA suggest that pain reduction is superior in patients who receive HMW HA as opposed to LMW HA. CONCLUSION: This review highlights differences between IA-HA characteristics, and how important the molecular weight, derivation of the product, and structure are to variances in reported clinical outcomes to treat osteoarthritis (OA) of the knee. HMW IA-HAs have shown greater efficacy compared to the alternative of LMW products, while avian-derived and cross-linked products have potentially demonstrated an increase in inflammatory events over non-avian-derived, non-cross-linked HAs.

[Hyaluronic acid in the treatment of osteoarthritis of various localization: A review].

The article discusses the treatment of osteoarthritis (OA), the prevalence of which is high, and according to some forecasts it will increase by 50% in the next 20 years. The authors emphasize the high comorbidity among patients suffering from OA and high cardiovascular and gastrointestinal risks with frequent use of NSAIDs, the volume of consumption of which is constantly increasing. Discussing recommendations for the treatment of patients with OA, the article focuses on the use of hyaluronic acid (HA) preparations in the treatment of OA. The mechanisms of anti-inflammatory and chondroprotective actions of HA in the joint, its effect on cartilage and synovial membrane are discussed. Attention is drawn to the fact that, despite more than 30 years of experience in the effective use of HA preparations in the treatment of OA, this procedure is still a subject of controversy among international professional communities. The article presents data from meta-analyses and systematic reviews confirming the effectiveness of the use of intra-articular management of HA preparations in OA of various localization (knee joints, hip joints, hand joints). In conclusion, the recommendations of the technical expert group established at the International Symposium on Intra-Articular Treatment are given to determine the criteria for the successful administration of HA in OA of various localizations, as well as predictors of success and non-success of therapy with HA drugs. The experts identified indications, contraindications for intra-articular administration of HA preparations, as well as conditions associated with an increased risk of therapy failure. In conclusion, the authors draw conclusions about the importance of using HA preparations for intra-articular administration for the treatment of OA, starting from the early stages, following the recommendations of experts.

Co-formulations of adalimumab with hyaluronic acid/polyvinylpyrrolidone to combine intraarticular drug delivery and viscosupplementation.

Polymer-based formulations present an attractive strategy in intraarticular drug-delivery to refrain biologicals from early leakage from the joint. In this study, co-formulations of hyaluronic acid and polyvinylpyrrolidone were investigated for their potential as viscosupplements and their influence on the transsynovial loss of adalimumab. For this purpose, polymer mixtures were evaluated for their viscosity and elasticity behavior while their influence on the permeation of adalimumab across a porcine ex-vivo synovial membrane was determined. Hyaluronic acid showed strong shear thinning behavior and exhibited high viscosity and elasticity at low motions, while combinations with polyvinylpyrrolidone provided absorption and stiffness at high mechanical stress, so that they can potentially restore the rheological properties of the synovial fluid over the range of joint motion. In addition, the formulations showed significant influence on transsynovial permeation kinetics of adalimumab and hyaluronic acid, which could be decelerated up to 5- and 3-fold, respectively. Besides viscosity effects, adalimumab was retained primarily by an electrostatic interaction with hyaluronic acid, as detected by isothermal calibration calorimetry. Furthermore, polymer-mediated stabilization of the antibody activity was detected. In summary, hyaluronic acid - polyvinylpyrrolidone combinations can be efficiently used to prolong the residence of adalimumab in the joint cavity while simultaneously supplying viscosupplementation.

A composite device for viscosupplementation treatment resistant to degradation by reactive oxygen species and hyaluronidase.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.