Medium Molecular Weight Hyaluronic Acid Research Articles

Low, medium, and high molecular weight hyaluronic acid effects on human dental pulp stem cells in vitro

Hyaluronic acid (HA), an extracellular biopolymer found throughout the human body, holds promise as a biocompatible and biodegradable scaffold material. High molecular weight (HMW) HA degrades, generating low molecular weight (LMW) fragments with distinct properties. These fragments can influence the behaviour of cells, including human dental pulp stem cells (hDPSCs) incorporated into HA-containing hydrogels or scaffolds. Therefore, a comprehensive examination of the impact of a range of HA molecular weights on hDPSCs is essential before designing HA-based scaffolds for these cells. hDPSC lines were cultured with LMW HA (800 Da, 1600 Da, 15 kDa), medium molecular weight HA (237 kDa), or HMW HA (1500 kDa) over six passages. The various molecular weights had negligible effects on hDPSCs viability, morphology, adhesion, or relative telomere length. Furthermore, the expression of key surface stemness markers (CD29, CD44, CD73, CD90) remained unaltered. HA did not induce osteogenic, chondrogenic, or adipogenic differentiation. Moreover, the potential for chondrogenic and osteogenic differentiation was not adversely affected by LMW or HMW HA. Various molecular weights of HA seem safe, biocompatible and therefore suitable components for hDPSCs-containing scaffolds. These findings affirm that the hDPCSs will not be negatively affected by HA fragments resulting from scaffold degradation.

Comparison of Four Treatment Protocols with Intra-Articular Medium Molecular Weight Hyaluronic Acid in Induced Temporomandibular Osteoarthritis: An Experimental Study.

The aim was to compare the effect between a single intra-articular infiltration (1i) and two infiltrations (2i) of medium molecular weight hyaluronic acid (MMW-HA) of high viscosity (HV) and low viscosity (LV) on the histopathological characteristics of temporomandibular joint (TMJ) osteoarthritis (OA) induced in rabbits. An experimental study was conducted on Oryctolagus cuniculus rabbits, including 42 TMJs, distributed between (1) TMJ-C, control group; (2) TMJ-OA, group with OA; (3) TMJ-OA-wt, group with untreated OA; (4) group treated with HA-HV-1i; (5) group treated with HA-HV-2i; (6) group treated with HA-LV-1i; and (7) group treated with HA-LV-2i. The results were evaluated using the Osteoarthritis Research Society International (OARSI) scale and descriptive histology considering the mandibular condyle (MC), the articular disc (AD), and the mandibular fossa (MF). The Kruskal-Wallis test was used for the statistical analysis, considering p < 0.05 significant. All treated groups significantly decreased the severity of OA compared to the TMJ-OA-wt group. The HA-HV-2i group showed significant differences in the degree of OA from the TMJ-OA group. The degree of OA in the HA-HV-2i group was significantly lower than in the HA-LV-1i, HA-LV-2i, and HA-HV-1i groups. The protocol that showed better results in repairing the joint was HA-HV-2i. There are histological differences depending on the protocol of the preparation used: two infiltrations seem to be better than one, and when applying two doses, high viscosity shows better results.

Hyaluronic acid: An overlooked extracellular vesicle contaminant.

The variable presence of contaminants in extracellular vesicle (EV) samples is one of the major contributors to a lack of inter-study reproducibility in the field. Well-known contaminants include protein aggregates, RNA-protein complexes and lipoproteins, which resemble EVs in shape, size and/or density. On the contrary, polysaccharides, such as hyaluronic acid (HA), have been overlooked as EV contaminants. Here, it is shown that low and medium molecular weight HA polymers are unexpectedly retained to some extent in EV fractions using two common isolation methods known for high purity: size-exclusion chromatography and tangential flow filtration. Although these isolation techniques are capable of efficient removal of non-EV-associated proteins, this is not the case for HA polymers, which are partially retained in a molecular weight-dependent manner, especially with size-exclusion chromatography. The supramolecular structure and hydrodynamic size of HA are likely to contribute to isolation in EV fractions of filtration-based approaches. Conversely, HA polymers were not retained with ultracentrifugation and polymer-based precipitation methods, which are known for co-isolating other types of contaminants. HA has a broad range of immunomodulatory effects, similar to those ascribed to various sources of EVs. Therefore, HA contaminants should be considered in future studies to avoid potential inaccurate attributions of functional effects to EVs.

Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration.

Pharmacological therapies in lung diseases are nowadays useful in reducing the symptomatology of lung injury. However, they have not yet been translated to effective treatment options able to restore the lung tissue damage. Cell-therapy based on Mesenchymal Stem Cells (MSCs) is an attractive, as well as new therapeutic approach, although some limitations can be ascribed for therapeutic use, such as tumorigenicity and immune rejection. However, MSCs have the capacity to secrete multiple paracrine factors, namely secretome, capable of regulating endothelial and epithelial permeability, decrease inflammation, enhancing tissue repair, and inhibiting bacterial growth. Furthermore, Hyaluronic acid (HA) has been demonstrated to have particularly efficacy in promoting the differentiation of MSCs in Alveolar type II (ATII) cells. In this frame, the combination of HA and secretome to achieve the lung tissue regeneration has been investigated for the first time in this work. Overall results showed how the combination of HA (low and medium molecular weight HA) plus secretome could enhance MSCs differentiation in ATII cells (SPC marker expression of about 5 ng/mL) compared to the only HA or secretome solutions alone (SPC about 3 ng/mL, respectively). Likewise, cell viability and cell rate of migration were reported to be improved for HA and secretome blends, indicating an interesting potentiality of such systems for lung tissue repair. Moreover, an anti-inflammatory profile has been revealed when dealing with HA and secretome mixtures. Therefore, these promising results can allow important advance in the accomplishment of the future therapeutic approach in respiratory diseases, up to date still missing.

The effects of the molecular weights of hyaluronic acid on the immune responses

BackgroundThe molecular weight of hyaluronic acid (HyA) depends on the type of organ in the body. When HyA of the desired molecular weight is implanted into the human body for regeneration of damaged tissue, it is degraded by hyaluronidase in associated with an inflammatory response. This study sought to evaluate the effects of HyA molecular weight and concentration on pro- and anti-inflammatory responses in murine macrophages.MethodsThe structures and molecular weights of HyAs (LMW-10, MMW-100, MMW-500, and HMW-1,500) were confirmed by 1 H NMR and gel permeation chromatography (GPC), respectively. After treatment of murine macrophages with a low (10 µg/mL) or high (100 µg/mL) concentration of each molecular weight HyA, cells were stimulated with lipopolysaccharide (LPS) and changes in immune response in both LPS-stimulated and untreated macrophages were evaluated by assessing nitric oxide (NO) production, and analyzing expression of pro- and anti-inflammatory genes including by RT-PCR.ResultsMolecular weights of LMW-10, MMW-100, MMW-500, and HMW-1,500 were 13,241 ± 161, 96,531 ± 1,167, 512,657 ± 8,545, and 1,249,500 ± 37,477 Da, respectively. NO production by LPS-stimulated macrophages was decreased by increasing concentrations and molecular weights of HyA. At a high concentration of 100 µg/mL, HMW-1,500 reduced NO production in LPS-stimulated macrophages to about 45 %. Using NanoString technology, we also found that the immune-related genes TNF-α, IL-6, IL-1β, TGF-β1, IL-10, IL-11, CCL2, and Arg1 were specifically over-expressed in LPS-stimulated macrophages treated with various molecular weights of HyA. An RT-PCR analysis of gene expression showed that HMW-1,500 decreased expression of classically activated (M1) macrophage genes, such as TNF‐α, IL-6, CCL2, and IL-1β, in LPS-stimulated macrophages, whereas medium molecular-weight HyA (MMW-100 and MMW-500) instead increased expression levels of these genes. HMW-1,500 at a high concentration (100 µg/mL) significantly decreased expression of pro-inflammatory genes in LPS-stimulated macrophages. Expression of genes associated with anti-inflammatory responses (M2 phenotype), such as TGF-β1, IL-10, IL-11, and Arg1, were increased by high concentrations of MMW-500 and HMW-1,500 in LPS-stimulated macrophages.ConclusionsHigh molecular-weight HyA (i.e., > 1,250 kDa) inhibits pro-inflammatory responses in LPS-stimulated macrophages and induces anti-inflammatory responses in a concentration dependent manner.

Comparing the efficacy of hyaluronic acid products with various molecular weights as mono and combined with chondroitin sulfate regimens in treatment of patients with stage I–III knee osteoarthritis

Aim: to evaluate the effectiveness of hyaluronic acid (HA) preparations with different molecular weights and in combination with chondroitin sulfate (HS) for intra-articular (IA) injections in the treatment of patients with stage I–III knee OA.Subjects and methods. IA HA injections were performed 160 patients with primary and post-traumatic knee OA of the I–III stages at the department of traumatology-orthopedics, V.A. Nasonova Research Institute of Rheumatology for the period from September 2017 to June 2019. Patients were divided into 4 groups. Group 1 consisted of 80 patients treated with low molecular weight (LMW) HA, group 2–20 patients treated with medium molecular weight (MMW) HA, group 3–30 patients treated with high molecular weight (HMW) HA, and group 4–30 patients who were intraarticular introduced HA with HS. The course of IA injections was 2 for LMW, HMW, and HA with HS, and 3 for MMW HA. Injections were performed with an interval of 1 week. To evaluate the results of treatment, we studied the intensity of pain according to VAS and the total score of KOOS before treatment and on follow-up examinations 1, 3 and 6 months after the course of IA HA injections.Results. The maximum reduction in pain with IA HA injections at stage I of knee OA occurred by 3 months after the course of treatment. Moreover, improvement was detected by 1 month in 84.3% of cases, and remained until the end of the study in 71.1% of patients. All HA preparations used in stage I of knee OA were effective. At stage II of the knee OA after 3 months after the course of IA HA, different efficiencies of HA preparations were revealed. So, in the groups of LMW, MMW and HA with HS, the improvement persisted up to 3 months, and in the group of HMW HA – up to 1 month. After 3 months, the best results were shown by HA with HS, by 6 months the results were comparable. IA HA injections at the II stage of knee OA led to good and excellent results 1 month after the course of treatment in 53.9% of cases, but by the end of the study, improvement remained in only 30.8% of patients. In the case of the use of HA in stage III of the knee OA, the effectiveness of the studied drugs was comparable, and the maximum improvement was achieved by 1 month. The positive effect of IA HA injections in patients with stage III of the knee OA one month after the course of treatment was obtained in 40.6% of cases, by 3 months it decreased to 18.8%, and by 6 months – to 15.7% of patients.Conclusions. IA injections of HA at stage I of the knee OA is a highly effective method of conservative treatment, which allows to relieve pain and improve the condition of the knee joint for a period of 6 months or more. The use of HA preparations at stage II of the knee OA allows reducing pain up to 3 months with IA injections of LMW and MMW HA, as well as HA with HS. HMW HA helps reduce pain intensity for a period of 1 month. The use of HA preparations in stage III of the knee OA leads to a short-term relief of symptoms of OA.

Effectiveness and Tolerability of Repeated Courses of Viscosupplementation in Symptomatic Hip Osteoarthritis: A Retrospective Observational Cohort Study of High Molecular Weight vs. Medium Molecular Weight Hyaluronic Acid vs. No Viscosupplementation.

Background: Nonsurgical management of symptomatic hip osteoarthritis needs real-world evidence. We evaluated the effectiveness and tolerability of US-guided intra-articular treatment of two hyaluronic acids (HAs) commercially available in Italy and investigated predictors of response. Methods: Outpatient records including three cohorts: 122 subjects treated with medium (1,500–3,200 kDa; Hyalubrix®) molecular weight (MW) or high (hylan G-F20; Synvisc®) MW HAs and 20 controls taking NSAIDs/analgesics on demand were retrospectively analyzed. Pain VAS score, WOMAC, NSAID/analgesic consumption, and causes of suspension were available at 1, 6, 12, and 24 months after first administration. As selection bias usually affects observational retrospective studies, a quasi-randomization process was attained by performing propensity score approach. Results: Propensity score adjustment successfully allowed comparisons among balanced groups of treatments. VAS and WOMAC considerably decreased over time in treated groups independently of the radiological grade (p<0.001). On the other hand, the control group showed only a slight and rather uneven variation in VAS. Mean score changes were comparable in both HA cohorts from the earliest stages (ΔVAS(HA1,500–3,200kDa)T1vsT0 = −20%; ΔVAS(hylan G-F20)T1vsT0 = −23%/ΔWOMAC(HA1,500–3,200kDa)T1vsT0 = −17%; ΔWOMAC(hylan G-F20)T1vsT0 = −19%), reaching a further substantial reduction after 12 months (ΔVAS(HA1,500–3,200kDa)T12vsT0 = −52%; ΔVAS(hylan G-F20)T12vsT0 = −53%/ΔWOMAC(HA1,500–3,200kDa)T12vsT0 = −45%; and ΔWOMAC(hylan G-F20)T12vsT0 = −47%). Almost 11% (=13/122) of ineffectiveness and few moderate local side effects 3% (=4/122) were detected. Conclusions: Viscosupplementation in a real-life setting seems to provide a sound alternative in pain management in comparison to oral NSAIDs/analgesics, guaranteeing a reduced intake of pain killer medications. Analgesic effectiveness, functional recovery, and reduced joint stiffness extend and improve over 12 and 24 months, suggesting that repeated administrations achieve an additive effect.

Use of viscosupplementation for the recovery of active football players complaining of knee pain.

ObjectiveThe aim of this study is to investigate the effect of intra-articular hyaluronic acid administration in active football players complaining of knee pain after sports activity. Efficacy and safety profiles of intra-articular hyaluronic acid and time needed for football players to recover and restart sports activity were examined.MethodsClinical data of active football players reporting knee pain after sports activity were included in this retrospective study. All patients who received an intra-articular injection at time 0 and after 2 weeks were included in the study. Patients underwent laboratory examination, knee X-ray, ultrasound, and clinical examination before receiving the intra-articular injection. Effusions or cysts were drained before injections. Lequesne index score, pain visual analog scale (VAS) score, and patient’s global assessment score were recorded at time 0 (day of the first injection), 1 and 2 days after the first injection, at 2 weeks (day of the second injection), and at follow-up visits. Only data from patients completing the follow-up were analyzed.ResultsData from 17 patients were analyzed: 16 males and one female, of which three were professional players (two males and one female) and 14 were nonprofessional players. The mean age of patients was 39.8±11.8 years. Two patients (one male and one female) showed joint effusion. Two patients reported relevant joint pain after injection that regressed without any medication. At the first week, all parameters examined indicated improvement that was maintained until the end of follow-up. One day after the first and second injection, patients reported a slight increase in pain VAS score, which was not statistically significant, and the pain resolved after 1 day. All patients successfully restarted playing after the first injection within 3.1±2.0 days and kept playing after the second injection following our indication (1 day of break).ConclusionThe use of a medium-molecular weight hyaluronic acid in football players affected by knee osteoarthritis seems efficacious and safe and resulted, in our experience, a stable improvement of symptoms; moreover, it allowed a rapid restart of sports activity. Larger studies on larger populations are needed to confirm these findings.

Effectiveness of Sequential Viscosupplementation in Temporomandibular Joint Internal Derangements and Symptomatology: A Case Series.

Viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of hyaluronic acid (HA). Although effective in some joints, there is not conclusive evidence regarding temporomandibular disorders. This case series described the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. This viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles.

Role of Hyaluronic Acid on Apolipoprotein A1 and HDL-Mediated Cholesterol Efflux in Macrophages

Diabetic macroangiopathy are characterized by increased arterial stiffness and hyaluronic acid (HA) deposition in the large elastic arteries. It is noteworthy that systemic inhibition of HA synthesis by 4-methylumbelliferone interferes with the protective function of the endothelial glycocalyx, thereby facilitating leukocyte adhesion, inflammation, and progression of atherosclerosis. Apolipoprotein A1 (ApoA1) and High-density lipoprotein (HDL) mediates cholesterol efflux, which is the initial and rate-limiting step of reverse cholesterol transport preventing from atherosclerosis. The aim of the present study was to investigate the role of HA on ApoA1 and HDL-mediated cholesterol efflux in macrophages. Murine J774.1 macrophages and human THP-1 macrophages were labeled with 3H-cholesterol and incubated with ApoA1 (10 μg/ml) for 24 hours or HDL (50 μg/ml) for 4 hours. The percentage cholesterol efflux was calculated by dividing the media-derived radioactivity by the sum of the radioactivity in the media and the cells. The effect of HA on the cholesterol efflux was studied, adding that into the medium before the analysis of the cholesterol efflux. Under the existence of medium molecular weight HA (75-350 kDa), the HDL-mediated cholesterol efflux had significantly increased by 10.9% (n=4, p&amp;lt;0.01) in J774.1 macrophages. We also researched the relationship between HA and ATP-binding cassette transporter G1 (ABCG1), because expression of ABCG1 enhances cholesterol efflux to HDL. Predictably, HA significantly increased ABCG1 mRNA expression in macrophage (n=4, p&amp;lt;0.01), determined by Real-time Quantitative RT-PCR. These data suggest that HA increases HDL-mediated cholesterol efflux via ABCG1 in macrophages and the difference of molecular weight on HA may influence ApoA1 and HDL-mediated cholesterol efflux. The relationship between HA and cholesterol efflux might be one of the important mechanisms to prevent progression of atherosclerosis and diabetic macroangiopathy. Disclosure K. Matsuki: None. M. Ogura: None. M. Harada-Shiba: Advisory Panel; Self; Aegerion Pharmaceuticals. Speaker's Bureau; Self; Amgen Inc., Astellas Pharma US, Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Daiichi Sankyo Company, Limited, MSD K.K.. Research Support; Self; Sanofi, Aegerion Pharmaceuticals, Kowa Pharmaceuticals America, Inc..

The association between different molecular weights of hyaluronic acid and CHAD, HIF-1α, COL2A1 expression in chondrocyte cultures.

The aim of the present study was to investigate the effects of three different formulations of hyaluronic acid (HA): Low molecular weight (MW) Sinovial One®, medium MW Viscoplus® and high MW Durolane®, on chondrocyte proliferation and collagen type II (COL2A1), hypoxia-inducible factor 1α (HIF-1α) and chondroadherin (CHAD) expression in primary chondrocyte cultures. Standard primary chondrocyte cultures were established from osteochondral tissues surgically obtained from 6 patients with gonarthrosis. Cell morphology was evaluated using an inverted light microscope; cell proliferation was determined with a MTT assay and confirmed with acridine orange/propidium iodide staining. Levels of CHAD, COL2A1 and HIF-1α expression were assessed using specific TaqMan gene expression assays. The results demonstrated the positive effect of HA treatment on cell proliferation, which was independent from the MW. COL2A1 expression increased in the medium and high MW HA treated groups. It was observed that HIF-1α expression increased in the high MW treated group alone. CHAD expression increased only in the medium MW HA treated group. Evaluation of gene expression revealed that levels of expression increased as the duration of HA application increased, in the medium and high MW HA treated groups. In terms of increased viability and proliferation, a longer duration of HA application was more effective. Taken together, it may be concluded that the administration of medium and high MW HA may be a successful way of treating diseases affecting chondrocytes in a clinical setting.

Interrelationship between temporomandibular joint osteoarthritis (OA) and cervical spine pain: Effects of intra-articular injection with hyaluronic acid

Objective: The aim of this study was to evaluate cervical spine pain and function after five sessions of viscosupplementation with hyaluronic acid (HA) in patients with temporomandibular joint (TMJ) osteoarthritis.Methods: Forty-nine patients, (79% females, aged between 43–81 years), affected by TMJ osteoarthritis and concurrent cervical spine pain and limited function were recruited. All patients underwent a cycle of five weekly arthrocenteses and viscosupplementation with 1 ml of medium molecular weight HA according to the single-needle arthrocentesis technique. Outcome variables were TMJ pain (VAS), cervical active ranges of motion, cervical disability (NPDS), and presence of painful palpation sites. Assessments were carried out at baseline and at one, three and six months after the end of treatment protocol.Results: A significant reduction over time was shown both in TMJ pain levels and in NPDS values with respect to baseline (p < 0.001). Most parameters of active cervical range of motion showed an improvement with time. Benefits remained stable throughout six months after the viscosupplementation protocol.Conclusions: A protocol of TMJ intra articular arthrocentesis and viscosupplementation improved cervical function and reduced disability in patients with concurrent cervical spine pain. These findings add to the complex amount of literature on the relationship between temporomandibular disorders and cervical spine disorders.

Single- or multiple-session viscosupplementation protocols for temporomandibular joint degenerative disorders: a randomized clinical trial.

The aim of the study was to compare the effectiveness of two single-session protocols, either adopting high- (protocol A) or medium-molecular weight hyaluronic acid (protocol B), with the reference five-session protocol of temporomandibular joint (TMJ) lavage plus viscosupplementation (protocol C) in the management of chronic TMJ degenerative disorders. A randomized clinical trial (RCT) with ten participants per treatment group was designed, with multiple observation points, ending at 6months after treatment. Pain levels on a 10-point VAS scale were selected as the primary outcome variable to rate treatment effectiveness, along with a number of secondary outcome parameters. Findings showed that Group C patients had the highest decrease in pain levels. Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocols (P=0·024). Pairwise comparisons showed that the differences of treatment effect between the two single-session interventions were negligible (global P-value=0·93). On the contrary, the five-session protocol was significantly superior to both single-session protocols (global P-values ranging from 0·003 to 0·012). In conclusion, in a population of age-, sex-, and psychosocial aspects-matched study groups, the standard of reference five-session protocol proved to be superior at 6months as far as the decrease in pain levels was concerned, whilst there were no differences between the two single-session interventions. The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation.

Effectiveness of treatment with viscosupplementation in temporomandibular joints with or without effusion

The objective of this study was to determine whether the effectiveness of viscosupplementation with hyaluronic acid (HA) in patients with temporomandibular joint (TMJ) degenerative disorders depends on the presence of intra-articular effusion. In this study of case–control design, two groups of 25 patients were recruited: patients with a clinical diagnosis of painful chronic TMJ osteoarthritis and magnetic resonance imaging (MRI) signs of TMJ degeneration, with (effusion group) or without (no effusion group) MRI evidence of TMJ effusion. All patients underwent five weekly single-needle arthrocenteses plus medium molecular weight HA and 6 months of follow-up. Several clinical outcome parameters were assessed. For all variables, analysis of variance (ANOVA) for repeated measures was performed to assess the existence of significant within-group and between-group treatment effects. Over time, both groups showed significant improvements in all outcome parameters, which were maintained at the 6-month follow-up (P<0.05). Between-group comparisons showed that the treatment effects did not differ significantly for either the primary outcome variable (pain levels: F=0.849, P=0.548) or secondary outcome variables (chewing efficiency: F=0.854, P=0.544; functional limitation: F=1.35, P=0.226; mouth opening: F=0.658, P=0.707). The null hypothesis that there are no differences in treatment effectiveness between patients with and without effusion could not be rejected.

Comparison of 2 Hyaluronic Acid Drugs for the Treatment of Temporomandibular Joint Osteoarthritis

To compare the effectiveness of 2 treatment protocols providing 5 weekly temporomandibular joint (TMJ) arthrocenteses immediately followed by injections of 2 different molecular weight hyaluronic acid (HA) drugs to manage symptoms in patients with inflammatory-degenerative TMJ disease. Patients with a Research Diagnostic Criteria for Temporomandibular Disorders diagnosis of osteoarthritis were randomly assigned to 1 of 2 study groups receiving either low- or medium-molecular weight HA after arthrocentesis. The level of maximum pain at chewing was the primary outcome variable, and maximum pain at rest, subjective chewing efficiency, functional limitation, treatment tolerability, perceived treatment effectiveness, and jaw range-of-motion function in millimeters were the secondary outcomes. All variables were assessed and compared between groups at baseline, at the end of treatment, and 3 months later. Forty subjects entered the study. At the end of the follow-up period, all the outcome variables improved in both groups of patients. A between-group comparison of changes over time showed that differences were not significant for any of the outcome variables, that is, pain at chewing (F = 0.056, P = .815), pain at rest (F = 0.383, P = .541), chewing efficiency (F = 0.050, P = .825), functional limitation (F = 0.268, P = .609), and mouth opening (F = 0.003, P = .954). In addition, no between-group differences were shown for perceived treatment effectiveness and treatment tolerability. Similar positive effectiveness was shown for 2 treatment protocols for TMJ osteoarthritis (ie, 5-session single-needle arthrocentesis plus low- or medium-molecular weight HA).

Prolongation of lidocaine-induced epidural anesthesia by medium molecular weight hyaluronic acid formulations: pharmacodynamic and pharmacokinetic studies in the rabbit.

We evaluated the utility of medium molecular weight hyaluronic acid for prolonging the local anesthetic activity of lidocaine in a rabbit model of epidural analgesia. Equiviscous formulations were prepared as either a physical mixture of lidocaine hydrochloride and sodium hyaluronate (where drug release occurred via diffusion) or as a lidocaine-hyaluronate complex (where drug release occurred via diffusional and electrostatic processes). The novel hyaluronic acid formulations were functionally evaluated, relative to lidocaine solution, in an intact, conscious rabbit model. The hyaluronate formulations were well tolerated. The duration of sensory block and loss of weight-bearing was prolonged twofold by the lidocaine-hyaluronate complex relative to the solution (P < 0.05). In terms of motor block, flaccid paresis occurred after administration of the solution formulation, whereas only partial motor block was evident after administration of the viscous formulations. Pharmacokinetic modeling of the lidocaine plasma concentration-time data indicated that the rate of drug absorption from the lidocaine-hyaluronate complex was decreased fourfold relative to the solution (P < 0.05). These observations indicate that ionic complexes of local anesthetics with medium molecular weight hyaluronic acid may offer advantages for the prolongation of epidural analgesia.

Prolongation of Lidocaine-Induced Epidural Anesthesia by Medium Molecular Weight Hyaluronic Acid Formulations

We evaluated the utility of medium molecular weight hyaluronic acid for prolonging the local anesthetic activity of lidocaine in a rabbit model of epidural analgesia.Equiviscous formulations were prepared as either a physical mixture of lidocaine hydrochloride and sodium hyaluronate (where drug release occurred via diffusion) or as a lidocaine-hyaluronate complex (where drug release occurred via diffusional and electrostatic processes). The novel hyaluronic acid formulations were functionally evaluated, relative to lidocaine solution, in an intact, conscious rabbit model. The hyaluronate formulations were well tolerated. The duration of sensory block and loss of weight-bearing was prolonged twofold by the lidocaine-hyaluronate complex relative to the solution (P < 0.05). In terms of motor block, flaccid paresis occurred after administration of the solution formulation, whereas only partial motor block was evident after administration of the viscous formulations. Pharmacokinetic modeling of the lidocaine plasma concentration-time data indicated that the rate of drug absorption from the lidocaine-hyaluronate complex was decreased fourfold relative to the solution (P < 0.05). These observations indicate that ionic complexes of local anesthetics with medium molecular weight hyaluronic acid may offer advantages for the prolongation of epidural analgesia. (Anesth Analg 1995;80:740-6)