The results of preventing postoperative achilles tendon adhesion using cross-linked and non-cross-linked hyaluronic acid, a study with rat model.

BACKGROUND: There are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries. PURPOSE: This study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair. METHODS: Twenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments. RESULTS: Non-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects. CONCLUSIONS: Non-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.

Can Hyaluronic Acid Combined with Chondroitin Sulfate in Viscosupplementation of Knee Osteoarthritis Improve Pain Symptoms and Mobility?

The objective of the present study was to assess the effect of intra-articular Hyaluronic acid (HA) and Chondroitin sulfate (CS) supplementation (Hialurom® Hondro (HH)) on pain symptoms and joint mobility. In total, 60 mg/mL sodium hyaluronate and 90 mg/mL CS were administered to 21 patients (17 females and 4 males) respecting the in-force requirements, excluding patients with some specific comorbidities. In addition to the clinical study (where the pain intensity (severity) and joint mobility were assessed), rheological characterization was conducted evaluating the following parameters: elastic modulus (G'), loss modulus (G″) oscillatory frequency (fc) at 0.5 Hz and 2.5 Hz, crossover frequency (fc), relaxation time (λ) where it was noticed that the addition of chondroitin sulfate (CS) to sodium hyaluronate (SH) significantly enhances and improves the viscoelastic properties, particularly at higher shear frequencies. A significant decrease in pain intensity felt by the subjects was found, from 7.48 (according to Wong-Baker scale)-pain close to 8 (the patient is unable to perform most activities), to more reduced values of 5.86-at 6 weeks after injection, 4.81-at 3 months after injection, and 5.24-at 6 months after injection, improvements in symptoms was fast and durable. Data related to the evolution of joint mobility show that at 6 weeks after injection, the mobility of joints increased by 17.8% and at 6 months by 35.61%. No serious adverse events were reported with undesired effects so that they would impose additional measures. Better resistance to enzymatic degradation and free radicals could be expected from the synergic combination of sodium hyaluronate and chondroitin sodium sulfate, this having a special importance for the patients, granting them the ability to perform more ample movements and reducing dependency on attendants, thus increasing quality of life.

A Meta-Analytical Way of Systematizing the Use of Hyaluronan Gels for the Relief of Osteoarthritis, Compared with New Treatment Alternatives.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for the viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement but for its use adapted to the peculiarities of the disease manifestation and of the patients. A "broad" comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation therapy and its main challenger of clinical interest, the platelet-rich plasma treatment. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using algorithms implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, we adhere in a documented way to the opinion that HA-based products, currently under circumspection, are still clinically useful.

Comparison of outcomes with intra-articular hyaluronic acid vs corticosteroids after TMJ arthrocentesis: a systematic review and meta-analysis.

OBJECTIVE: This review aimed to examine differences in outcomes with the use of intra-articular hyaluronic acid (HA) vs corticosteroids (CS) after temporomandibular joint (TMJ) arthrocentesis. METHODS: Studies were searched on PubMed, Embase, Web of Science, and Google Scholar up to 15th January 2024. Randomized controlled trials (RCTs) comparing HA with CS after TMJ arthrocentesis were included. The outcomes were pain and maximal mouth opening (MMO). RESULTS: Ten articles corresponding to nine RCTs were included. There was no statistically significant difference in pain scores at 1 week (MD: -0.30 95% CI: -1.25, 0.65 I2=0%), 1 month (MD: -0.55 95% CI: -1.23, 0.13 I2=0%), and 6 months (MD: -0.57 95% CI: -2.10, 0.96 I2=58%) between the two groups. However, pain scores were found to be significantly lower in the HA group at 3 months (MD: -1.07 95% CI: -1.84, -0.31 I2=0%). No statistically significant difference was noted in MMO at 1 week (MD: 0.78 95% CI: -1.79, 3.35 I2=0%), 1 month (MD: 0.32 95% CI: -1.83, 2.46 I2=0%), and 3 months (MD: -0.41 95% CI: -3.90, 3.07 I2=0%) between the two groups. Descriptive analysis for studies not included in the meta-analysis also presented similar results. CONCLUSIONS: Low-quality evidence suggests that both intra-articular HA and CS have similar efficacy in improving pain scores and MMO after TMJ arthrocentesis.

Ultrasound-Guided Hip Injections with High Density Hyaluronic Acid: Outcome at One Year Follow Up.

Background: The ultrasound-guided viscosupplementation of the hip joint with hyaluronic acid (HA) is considered a standard procedure among the conservative treatments for hip arthritis. The aim of this study was to evaluate the clinical benefit and the incidence of adverse events of the technique in an observational study at one year follow up. Methods: We evaluated a consecutive series of 85 patients with a diagnosis of symptomatic arthritis who underwent intra-articular ultrasound-guided hyaluronic acid injections. The scales used for evaluation were modified Harris Hip Score (mHHS), WOMAC (Western Ontario and McMaster University), and Hip Outcome Score (HOS) with subscale Sport (HOSs), for pain the Visual Analogic Scale (VAS). The patients were classified according to Tonnis' radiological classification of arthritis (range 0-3): 20 patients (grade 0), 32 (grade 1), 18 (grade 2), 15 (grade 3). Results: At last follow up, all the scales increased: mHHS from 59.35 to 82.1, HOS from 69.45 to 78.53, HOss from 47.4 to 58.11, VAS from 6.09 to 3.97, WOMAC from 33.2 to 31.5 (p < 0.05 for all the parameters); the results were elaborated with GraphPad Prism v5.0 (Prism Software La Jolla, CA, USA) using Wilcoxon's test. A total of 13 patients out of 85 needed arthroplasty, all classified as Tonnis grade 3. No serious adverse events were noted due to the procedure. Conclusions: Based on our findings, indication for the use of hyaluronic acid is limited to patients with mild to moderate arthritis. Patients in advanced arthritis refusing replacement surgery and asking for this treatment should be informed about the poor results of the technique even in the short term.

A Cross-Sectional Study of Factors Predicting the Duration of the Efficacy of Viscosupplementation in Knee Osteoarthritis.

Background: An advanced radiological stage and obesity are predictive of poorer and shorter responses to viscosupplementation in patients with knee osteoarthritis (OA). Very little is known regarding the impact of other factors such as sport practice, comorbidities, or anatomical features of OA. Methods: This study aimed to investigate patients' and OA characteristics associated with the duration of the effectiveness (DE) of viscosupplementation in patients with knee OA. It was a cross-sectional, single-centre clinical trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigators collected data regarding demographic and radiographic features (Kellgren-Lawrence grade and involved knee compartments), dosing regimen (single or repeat injections), the presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, the number of previous viscosupplementations, and comorbidities. Patients completed a questionnaire including the self-assessment of DE (the number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, or athletic), and the level of sport activity (light, moderate, or intensive). Predictors of the DE were studied in bivariate and multivariate analyses. Results: In total, 105 patients (149 knees) were analysed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m2). The mean DE was 48.2 ± 24.8 weeks. In bivariate analysis, the predictors of a shorter DE were BMI > 27.5 kg/m2, more than three previous viscosupplementations, Kellgren-Lawrence grade 4, sedentary patients, and multicompartmental involvement. In the multivariate analysis, four independent factors remained associated with a shorter DE: BMI > 27.5 kg/m2, multicompartmental knee involvement, number of viscosupplementations >3, and sedentary lifestyle. A statistically significant association between a longer DE and arterial hypertension was found, suggesting a beneficial effect of certain antihypertensive medications. Conclusions: This study confirms that being overweight significantly reduces the duration of the effectiveness of viscosupplementation. It also shows that viscosupplementation is more lastingly effective in unicompartmental OA and among active or athletic patients. The duration of effectiveness decreases when the treatment is repeated more than three times.

Three once-weekly intra-articular injections of Hylan G-F 20 significantly improve pain relief compared with placebo in patients with chronic idiopathic knee osteoarthritis: a single-centre, evaluator-blinded and patient-blinded, randomized controlled trial.

Background: Clinical trials on the use of viscosupplementation with hyaluronic acid (HA) in patients with knee osteoarthritis (KOA) are inconsistent, making it challenging to determine its value in clinical practice. One issue is the availability of various HA products on the market; differences in their chemical features can impact patient outcomes. Herein, we assess the efficacy and safety of three once-weekly intra-articular (IA) injections of Hylan G-F 20, a high-molecular-weight and highly crosslinked HA product, in patients with KOA. We hypothesized that Hylan G-F 20 would provide significant pain relief with no increased safety risk compared with IA saline (placebo). Methods: This was a 26-week, patient-blinded and evaluator-blinded, single-centre, randomized placebo- controlled trial. Men or women ≥18 years of age with Larsen grade II or III KOA were included. Patients received IA injections of either Hylan G-F 20 or placebo once a week for 3 weeks. The primary endpoints were the week 12 and 26 visits. Primary efficacy outcomes included visual analogue scale (VAS) pain scores, patient activity level and an overall assessment of clinical condition. Secondary outcomes included adverse events (AEs) that emerged during treatment. The primary analysis included the intention-to-treat population. An alpha level of 0.05 was used in the statistical analysis. Results: Thirty patients were included in the intention-to-treat population (15 per group). All efficacy outcomes were statistically significant in favour of Hylan G-F 20, except night pain and inactivity stiffness, for both patient- assessed (all p=0.0001 at week 12) and evaluator-assessed (all p=0.0001 at week 12 and p=0.0004-0.0180 at week 26) measurements. There was also a greater proportion of symptom-free patients and those with a >50% improvement in their VAS scores, except night pain, in the Hylan G-F 20 group (p=0.001-0.003 in patient-assessed scores and p<0.0001 to 0.002 in evaluator-assessed scores at week 12). Two patients, one in each group, experienced an AE; no sequelae occurred, and no special treatment was required for either AE. No patients withdrew from the study prematurely due to an AE. Conclusion: In patients with chronic idiopathic KOA, Hylan G-F 20 provides significant improvements in pain relief compared with placebo with no added safety concerns.

Efficacy of new active viscosupplements on the behavior of an experimental model of osteoarthritis. / Eficacia de nuevos viscosuplementos activos en el comportamiento de un modelo experimental de osteoartritis.

OBJECTIVE: To evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs. MATERIAL AND METHODS: Experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V). In groups II to V, the infiltration of the corresponding compound was carried out spaced one week apart. Macroscopic histological analysis was performed using a scale based on the Outerbridge classification for osteoarthritis. RESULTS: We observed that this osteoarthritis model is reproducible and degenerative changes similar to those found in humans are observed. The groups that were infiltrated with hyaluronic acid with curcumin-loaded nanoparticles (V), followed by the dexamethasone group (IV) presented macroscopically less fibrillation, exposure of subchondral bone and sclerosis (better score on the scale) than the control groups (I) (osteoarthritis without treatment), group (II) treated with commercial hyaluronic acid and hyaluronic acid with nanoparticles without drug (III). CONCLUSIONS: The use of active viscosupplements could have an additional effect to conventional hyaluronic acid treatment due to its antioxidant and anti-inflammatory effect. The most promising group was hyaluronic acid with nanoparticles that encapsulate curcumin and the second group was the one that encapsulates dexamethasone.

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.

Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.

INTRODUCTION: Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. METHODS: Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren-Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. RESULTS: Of 83 patients with KOA (Kellgren-Lawrence Grade, 2-3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. CONCLUSIONS: A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA.

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.

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.

Intra-articular injection of hyaluronic acid after arthroscopic surgery fails to provide additional benefit for symptomatic degenerative arthropathy patients: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study aimed to provide the evidence of the role of addition hyaluronic acid immediate after arthroscopy in pain relief and functional recovery. Methods: A multiple databases search of the PubMed, the Cochrane Library, and Embase was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to identify randomized controlled trials that evaluate the effect the hyaluronic acid compared with placebo addition immediately after arthroscopy for degenerative arthropathy. Data related to postoperative pain using the visual analog scale, and functional scores, were extracted and analyzed using the RevMan software. Results: A total of five randomized controlled trials were included in this study. All patients showed significant pain relief after surgery at 2 weeks and 2 months, but no statistically significant differences between the hyaluronic group and control group were observed at 2 weeks and 2 months, respectively. This meta-analysis did not find a difference of WOMAC score between the two groups at 2 weeks (MD: 3.07; 95% CI: -0.66 to 6.81; I2 =39%; P = 0.11) and 2 months (MD: 5.47; 95% CI: -0.69 to 11.62; I2 =57%; P = 0.08), respectively. Conclusion: For patients with symptomatic degenerative arthropathy, adding hyaluronic acid immediately after arthroscopic surgery did not appear to provide patients with more pain relief and better functional recovery.

EFFECTIVENESS OF VISCOSUPPLEMENTATION IN THE TREATMENT OF HEMOPHILIC ARTHROPATHY: A SYSTEMATIC REVIEW.

Objective: To describe the efficacy of using viscosupplementation in patients with hemophilic arthropathy (HA), on pain, limb functionality, and quality of life. Methods: A systematic review of the literature was performed following the PRISMA guidelines without limitations of language or year of publication. The search was performed on the following medical databases: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost, and PROQUEST in April 2020. The search used the following word: (hemophilia AND joint diseases) OR (haemophilic arthropathy OR hemophilic arthropathy) AND viscosupplementation. Results: The systematic review identified 127 articles, 10 of which were selected for data extraction and qualitative analysis. The 10 selected articles included 297 joints with HA in 177 hemophilic subjects. Our review showed positive results in alleviating pain and improving functional capacity, and quality of life. No major adverse effects were observed. Conclusion: There is a lack of scientific evidence regarding viscosupplementation with hyaluronic acid, but the results presented in this research suggest that it is an effective and safe therapeutic option to alleviate pain and improve functional capacity in patients with HA. Level of Evidence II, Systematic Review.

Objetivo: Descrever o uso da viscossuplementação com ácido hialurônico em pacientes com artropatia hemofílica (HA), sua eficácia na dor, a funcionalidade do membro e a qualidade de vida após sua aplicação. Métodos: Revisão sistemática da literatura (RSL) que seguiu as diretrizes PRISMA, sem limitação de idioma ou ano de publicação. A pesquisa foi realizada em abril de 2020 nas seguintes bases de dados médicas: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost e ProQuest. A estratégia de pesquisa foi: (hemofilia AND joint disease) OR (artropatia hemofílica OU artropatia hemofílica) E viscossuplementação. Resultados: A RSL identificou 127 artigos, dos quais 10 foram selecionados para extração de dados e análise qualitativa. Os 10 artigos selecionados incluíram 297 articulações com AH em 177 indivíduos hemofílicos. Nossa revisão mostrou resultados positivos na melhora da dor, na capacidade funcional e na qualidade de vida. Não foram observados efeitos adversos importantes. Conclusão: A evidência científica atual a respeito da viscossuplementação com ácido hialurônico é escassa, mas os resultados apresentados nesta pesquisa sugerem que é uma opção terapêutica eficaz e segura para diminuir a dor e melhorar a capacidade funcional em pacientes com AH. Nível de Evidência II, Revisão Sistemática.

Large Variations in Resistance to Degradation between Hyaluronic Acid Viscosupplements: A Comparative Rheological Study.

AIM: To compare the resistance to degradation of linear and cross-linked viscosupplements using a rheological model combining mechanical and oxidative stresses, mimicking what happens inside the joint following HA injection. METHODS: The rheological properties of 8 HAs were measured using a stress-imposed Rheometer DHR3. Strain sweeps were carried out to evaluate the rheological properties at rest from 0.001 to 3000% at a frequency of 1 Hz. The complex modulus G*, in Pa, and the phase tangent tan δ, dimensionless, in the linear viscoelastic domain (LVED) were extracted. The oxidation tests were conducted by exposing the product to H2O2 for 30 minutes. The effect of oxidation was evaluated by measuring variations of G* and tan δ, using an oscillation time sweep. Those tests were carried out at a frequency of 1 Hz and at 1% strain in the LVED. RESULTS: At rest, the different samples exhibited various viscous behaviors. During mixing process, G* decreased from -6.4% to -31.3%. G* of low-molecular-weight HAs decreased more than that of medium molecular weight (MW) and cross-linked products. After oxidative stress, G* variation ranged from -10.1% to -46.3%. Cross-linked HAs and those containing mannitol resisted the best to degradation. CONCLUSIONS: We showed large variations in resistance to degradation between viscosupplements. The duration of effectiveness of these products deserves to be compared in randomized clinical studies.

Multidisciplinary Rehabilitation after Hyaluronic Acid Injections for Elderly with Knee, Hip, Shoulder, and Temporomandibular Joint Osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative joint condition characterized by cartilage deterioration, joint inflammation, and functional limitations, particularly impacting the elderly population. Rehabilitation and hyaluronic acid (HA) injections are common therapeutic approaches routinely used in clinical practice, but their synergistic potential is far from being fully characterized. Thus, the aim of this narrative review was to elucidate the multilevel benefits and synergies of integrating these two approaches in multidisciplinary OA rehabilitation. This narrative review follows the scale for the assessment of narrative review articles (SANRA) criteria and involves a comprehensive literature search from July to August 2023. Two independent reviewers screened studies, including those involving human subjects with OA, rehabilitation strategies, and outcomes following HA injection, published in English. Results: HA injections might improve joint biomechanics, reducing friction, absorbing shocks, and potentially regulating inflammation. Rehabilitation plays a pivotal role in strengthening muscles, increasing the range of motion, and enhancing overall function. Optimizing rehabilitation following HA injection might provide additional benefits in joint health. OA management requires a multidisciplinary approach integrating HA injections, rehabilitation, and personalized care. Challenges in patient adherence and healthcare resources currently exist, but emerging technologies offer opportunities to enhance patient engagement and monitoring optimizing sustainability and outcomes of patients with knee, hip, shoulder, and temporomandibular joint OA.

Interventional Techniques for the Management of Knee Osteoarthritis: A Literature Review.

Osteoarthritis of the knee is a prevalent condition that causes pain, discomfort, and disability that can severely impact the quality of life. This literature review aims to review the various interventional pain management techniques available to treat knee osteoarthritis. It analyzes the efficacy of various interventions such as intra-articular corticosteroids, prolotherapy, viscosupplementation, platelet-rich plasma, and genicular nerve blocks with radiofrequency ablation or cryoneurolysis. We searched databases for studies published in the past 20 years. A total of 37 articles were included. The literature supports the idea that a comprehensive treatment plan consisting of the various aforementioned techniques can provide relief for patients while delaying or avoiding joint replacement surgery.

Ex Vivo Functional Benchmarking of Hyaluronan-Based Osteoarthritis Viscosupplement Products: Comprehensive Assessment of Rheological, Lubricative, Adhesive, and Stability Attributes.

While many injectable viscosupplementation products are available for osteoarthritis (OA) management, multiple hydrogel functional attributes may be further optimized for efficacy enhancement. The objective of this study was to functionally benchmark four commercially available hyaluronan-based viscosupplements (Ostenil, Ostenil Plus, Synvisc, and Innoryos), focusing on critical (rheological, lubricative, adhesive, and stability) attributes. Therefore, in vitro and ex vivo quantitative characterization panels (oscillatory rheology, rotational tribology, and texture analysis with bovine cartilage) were used for hydrogel product functional benchmarking, using equine synovial fluid as a biological control. Specifically, the retained experimental methodology enabled the authors to robustly assess and discuss various functional enhancement options for hyaluronan-based hydrogels (chemical cross-linking and addition of antioxidant stabilizing agents). The results showed that the Innoryos product, a niacinamide-augmented linear hyaluronan-based hydrogel, presented the best overall functional behavior in the retained experimental settings (high adhesivity and lubricity and substantial resistance to oxidative degradation). The Ostenil product was conversely shown to present less desirable functional properties for viscosupplementation compared to the other investigated products. Generally, this study confirmed the high importance of formulation development and control methodology optimization, aiming for the enhancement of novel OA-targeting product critical functional attributes and the probability of their clinical success. Overall, this work confirmed the tangible need for a comprehensive approach to hyaluronan-based viscosupplementation product functional benchmarking (product development and product selection by orthopedists) to maximize the chances of effective clinical OA management.

Could Hyaluronic Acid Be Considered as a Senomorphic Agent in Knee Osteoarthritis? A Systematic Review.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common causes of disability in elderly patients and tends to be a major burden on social and health care spending. Despite its severe socioeconomic impact, KOA remains, to date, an incurable disease. Due to its proper characteristics, KOA represents a favorable disease model for experimenting with senotherapeutics, a group of treatments that counteract the development of age-related disorders and chronic diseases. In recent years, the use of intra-articular hyaluronic acid (IAHA) in the treatment of diseases related to the wear and tear of the articular cartilage has been gaining popularity. Given its ability in joint lubrification, shock absorption, and cell signaling, our aim is to investigate, through the existing scientific literature, its potential role as a senomorphic agent, emphasizing its crucial function in KOA patients. Indeed, senomorphics are a particular group of senotherapeutics capable of modulating the functions and morphology of senescent cells to those of young cells or delaying the progression of young cells to senescent cells in tissues. METHODS: A search in the scientific literature (PubMed, Cochrane Library, and Google Scholar) was carried out from 2019 to 2023, thus the last 5 years. RESULTS: One hundred thirty-eight articles were found concerning the role of hyaluronic acid injections in KOA patients. In these studies, its therapeutic efficacy, its anti-inflammatory properties, and its low risk of side effects emerged. CONCLUSION: IAHA injections are a valuable treatment option for KOA while they can provide pain relief, improve joint function, and slow the progression of joint degeneration. The inhibitory effect of HA on MMP13 and its action as a senomorphic agent suggests that it may have additional benefits beyond its lubricating and shock-absorbing properties. In order to clarify its mechanisms of action and to optimize its clinical use, further studies are definitely needed.

Effectiveness of double-puncture temporomandibular joint arthrocentesis with viscosupplementation in different categories of severity - a prospective study.

This 3-year prospective study evaluated the efficacy of temporomandibular joint (TMJ) arthrocentesis with viscosupplementation in different severity stages based on the Dimitroulis classification (categories 2-4 were included). TMJ arthrocentesis was performed under local anaesthesia, and the protocol consisted of a double-puncture technique with lavage of ≥150 cc Ringer Lactate plus viscosupplementation. Incobotulinum toxin A was administered 10-15 days preoperatively in patients with concomitant masticatory myalgia. The primary outcome was TMJ pain, assessed by visual analogue scale (VAS, 0-10), and the secondary outcomes were the maximum mouth opening (MMO, mm) and myalgia degree (0-3). All outcomes were assessed on the intervention day (T0) and after the procedure (T1) (minimum 1 month and then 3 months, 6 months, 1 year and every year since). A total of 108 patients were enrolled (mean age of 43.1 ± 18.9 years); 86 (80%) were women and 22 (20%) were men. Preoperative pain was 4.02 ± 3.12 (mean ± SD), MMO was 38.10 ± 9.56 (mean ± SD) and myalgia degree was 1.80 ± 1.18 (mean ± SD). After an average of 215.4 days (31-1253 days), a statistically significant improvement of pain (P < 0.0001), MMO (P = 0.005) and myalgia degree (P < 0.0001) was observed. The overall successful outcome of TMJ arthrocentesis with viscosupplementation was 76%. The authors observed increased arthrocentesis effectiveness and success rate with viscosupplementation in Dimitroulis category 2 (88.6%) compared to 3-4 (71.4%). An association was found between arthrocentesis with viscosupplementation failure and painful myalgia (ρ = 0.477; P < 0.0001). Thirteen patients (12%) underwent a second TMJ intervention after finalising the present trial. With a low complication rate, TMJ arthrocentesis with viscosupplementation led to an overall benefit for all the included patients. This study reinforces the important role of minimally invasive TMJ arthrocentesis as a first treatment option, with better results in the early stages compared to more severe stages.