Hyaluronic Acid Formulations Research Articles

Efficacy of ophthalmic viscosurgical devices in maintaining corneal epithelial hydration and clarity: In vitro assessment

To determine the efficacy of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid (HA) in maintaining corneal hydration and optical clarity. Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. Experimental study. In porcine autopsy eyes, the effect of 13 ophthalmic viscosurgical devices (OVDs) (5 formulations of HPMC; 8 formulations of HA) in maintaining corneal hydration and optical clarity was tested. The main outcome variables were the time to reach optical clarity of the cornea during dissipation of the OVD and duration of corneal hydration. These variables were assessed after the first application of the OVD, after balanced salt solution application to rehydrate the gel matrix, and after the second application of OVD on top of the first layer. The study used 57 porcine eyes. High-molecular-weight HA 1.5% (zero shear viscosity [ZSV] 55,122 millipascal seconds [mPa.s]) took a significantly shorter time to reach optical clarity than HA 1.4% (ZSV 36,882 mPa.s) (P=.04). Hyaluronic acid 1.4% and HA 1.5% maintained corneal hydration significantly longer than HPMC 2.0% (P<.001). For corneal hydration during short-lasting surgical procedures such as cataract surgery, the results suggest using HPMC because it distributes quickly and provides an adequate duration of sufficient corneal hydration. For corneal hydration during prolonged surgical procedures, such as vitreoretinal surgery, results suggest using HA 1.5% in the formulation because it provides long-lasting corneal hydration. Dr. Prinz has a proprietary interest in Croma Pharma GmbH, Leobendorf, Austria. Dr. Findl is a scientific advisor to Croma Pharma GmbH. No other author has a financial or proprietary interest in any material or method mentioned.

Hyaluronic acid derivatives and their healing effect on burns, epithelial surgical wounds, and chronic wounds: A systematic review and meta‐analysis of randomized controlled trials

Hyaluronic acid (HA) is a polysaccharide common to most species and is found in many sites in the human body, including the skin and soft tissue. A systematic review of the literature and meta-analysis was performed to identify randomized controlled trials, evaluating the use of HA derivatives in healing burns, epithelial surgical, and chronic wounds. Nine studies were identified, which met the search criteria and clinical endpoints of complete healing and percent wound size reduction when using HA vs. either an active or passive comparator. It was found in the vast majority of randomized controlled trials (eight of nine) that HA derivatives significantly improved the healing of wounds vs. traditional therapies or placebo (either via complete healing or a significant reduction in wound size) occurring from burns, venous insufficiency, diabetes, neuropathic insufficiency, and surgical removal of the epithelial layer (for tattoo removal). In the other remaining trial, one formulation of HA was compared with another, with the higher concentration showing improved application characteristics. Further, it was found in a meta-analysis in subsets of patients with diabetic foot ulcers (neuropathic) that HA derivatives healed these types of wounds significantly faster than standard of care. These studies in aggregate show that HA derivatives accelerate the healing process in burns, epithelial surgical wounds, and chronic wounds.

A multicenter, randomized controlled trial comparing a single intra-articular injection of Gel-200, a new cross-linked formulation of hyaluronic acid, to phosphate buffered saline for treatment of osteoarthritis of the knee

To compare the safety and efficacy of a single intra-articular (IA) injection of a new cross-linked hyaluronic acid product, Gel-200, with phosphate buffered saline (PBS, control) in a multi-center randomized controlled trial in patients with symptomatic osteoarthritis (OA) of the knee. Patients were randomized 2:1 to receive a single injection of Gel-200 or PBS, after joint aspiration. The primary measure of effectiveness was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscores by 100-mm Visual Analog Scale (VAS); secondary outcomes included: total WOMAC, physical function, and stiffness subscores; patient and physician global assessments of disease activity, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responders, as well as safety of Gel-200. Of 379 patients randomized, safety was evaluated in 377 and efficacy in 375 (98.9% randomized) in the intent-to-treat population. Effectiveness of Gel-200 by WOMAC pain subscores was statistically significant at week 13 (P=0.037). Mean improvements from baseline in WOMAC pain subscores consistently favored Gel-200 at each visit. Effectiveness of Gel-200 treatment was statistically significant over weeks 3-13 by WOMAC total score, physical function, and physician global evaluations (P<0.05). The number of "strict" OMERACT-OARSI responders was statistically significant from weeks 6 to 13 (P=0.022). Adverse events were not significantly different between treatment groups, including serious adverse events considered related to study treatment. This trial demonstrated that a single injection of Gel-200 was well tolerated and relieved pain associated with symptomatic OA of the knee over 13 weeks. ClinicalTrials.gov NTC 00449696.

High-density Hyaluronic Acid for the Treatment of HIV-related Facial Lipoatrophy

Facial lipoatrophy is a stigmatizing hallmark of HIV. The injection of facial fillers has an essential role in the treatment of this condition. The objective of our study was to verify the safety and efficacy of a new formulation of high-density hyaluronic acid for the injectable treatment of HIV-related facial lipoatrophy. We treated with high-density hyaluronic acid injections HIV patients affected by moderate to severe facial lipoatrophy and evaluated them at last follow-up, at a minimum of 36 weeks. Physician-related outcomes included pre-and post-treatment ultrasound measurement of the soft-tissue thickness of the cheeks and qualitative assessment of aesthetic results by means of the Global Aesthetic Improvement Scale using pre- and post-treatment photos of the patients. Patient satisfaction outcomes were evaluated with the VAS-face scale and Freiburg test. Fifty-four patients were studied. The median number of treatment sessions was 3 and the median length of treatment was 5.5 months. The thickness of the soft tissues of the cheek increased significantly from 9.45 to 13.12 mm (p<0.0001). On the basis of the Global Aesthetic Improvement Scale, 87.5% of the patients were judged as "much improved" or "improved." Patient satisfaction at 1 year from the end of treatment was proven (VAS-face: 77.9; Freiburg questionnaire: 93.6% of patients were satisfied or very satisfied). Complications were limited to mild redness and swelling in the early postoperative period. Long-term improvement of facial contour and excellent patient satisfaction, in the absence of severe side effects, were obtained by the injection of high-density hyaluronic acid (STYLAGE® XL) in HIV patients with facial lipoatrophy.

Effect of lysine hyaluronate on the healing of decubitus ulcers in rehabilitation patients

Chronically hospitalized patients are often burdened with skin ulcerations, which may be persistent and even irreversible. Treatment with hyaluronic acid is widely used in the early phases of the ulcers to relieve symptoms and accelerate the healing process. The present study hypothesized that lysine hyaluronate (Lys-HA) (Lysial(®), Fatai-Nyl Srl; Jasper LLC, Lugano, Switzerland), a new formulation of hyaluronic acid, would improve the healing of decubitus ulcers more than the commonly used sodium hyaluronate (SH). A double-blind randomized controlled trial was designed to assess the superiority of Lys-HA versus SH on decubitus ulcer size reduction over a 15-day period, and on the time necessary to reach 50% lesion size regression. After a clinical evaluation, 50 hospitalized patients with decubitus ulcers were divided into three groups according to ulcer stage (stage 1: erythema and edema; stage 2: all-thickness skin destruction; stage 3: destruction of subcutaneous tissue) and randomized to receive Lys-HA or SH. Digital photographs were taken before the start of treatment, then every 3 days, and at the end of the study. Pre- and posttreatment differences in each group were tested using Student t tests and analysis of covariance with basis values as covariates. Ulcer reduction was greater in all the Lys-HA groups than SH groups. In stage 1 patients, 90% and 70% lesion size reductions were observed in the groups allocated to Lys-HA and SH, respectively (P<0.05). In stage 2 patients, 70% and 40% lesion size reductions were observed in the Lys-HA and SH groups, respectively (P<0.02). In stage 3 patients, 71% and 29% lesion size reductions were observed in the Lys-HA and SH groups, respectively (P<0.01). The regression time of 50% of lesion size was shorter in all the Lys-HA groups than SH groups (P<0.05). The use of Lys-HA in the healing process of decubitus ulcers provides an improved efficacy with respect to SH in hospitalized patients, suggesting its use from the early phases of ulceration.

Hyaluronic acid for the treatment of vocal fold scars

In vocal fold scars the lamina propria layer is lost or deficient. Lamina propria replacement therapy remains a clinical challenge because this layer has a highly specialized three-dimensional organization of extracellular matrix molecules and unique viscoelastic properties. Use of a polymer such as hyaluronic acid appears most promising for replacement therapy because it has the optimal viscoelasticity and also plays a role in the maturation and maintenance of vocal fold lamina propria. A variety of cross-linked hyaluronic acid formulations and growth factor therapies targeted to increase hyaluronic acid production have been used in the treatment of both acute and established vocal fold scars. Therapeutic strategies have focused on prevention of scar at the time of initial injury, and rejuvenation of lamina propria layer in established scars. Both strategies show improved histologic, viscoelastic, acoustic, and aerodynamic measures. Cross-linked hyaluronic acid formulations appear useful in the treatment of vocal fold scarring. Their use at the time of acute injury especially appears to lessen the degree of long-term scar formation and appears promising. While animal studies have demonstrated the safety profile of many hyaluronic acid formulations, further improvement in these materials and well designed and controlled human trials are needed to further establish the safety and efficacy of these materials and therapeutic approaches.

Hyaluronic Acid (Supartz®)

Hyaluronic acid (Supartz®; molecular weight 620-1170 kDa) is a sterile, viscoelastic, non-pyogenic solution that is indicated as a medical device for the treatment of pain in patients with osteoarthritis of the knee who have failed to respond adequately to conservative nonpharmacological therapy and simple analgesics. Intra-articular injections of Supartz® were significantly more effective than control injections, according to an integrated longitudinal analysis of pooled data from five randomized, double-blind, vehicle-controlled, multicentre trials in patients with osteoarthritis of the knee. Supartz®, compared with the phosphate-buffered saline control, significantly reduced the total Lesquésne Index score in the post-injection period. Data from the individual trials demonstrated that the reduction in the total Lesquésne Index score was significantly greater than the control in two of the five studies. According to another efficacy endpoint (the mean reduction in the Western Ontario and McMaster Universities Osteoarthritis Index), which was assessed in only one of these trials, Supartz® was significantly more effective than the control in reducing the pain and stiffness subscale scores. Clinical scores of pain/inflammation and visual analogue scale (VAS) scores of pain during walking improved from baseline values for up to 6 months after treatment with Supartz® or a corticosteroid, with no significant between-group differences, in a small, randomized, open-label, multicentre trial in patients with osteoarthritis of the knee. Intra-articular injections of both Supartz® and Synvisc®, as well as a phosphate-buffered saline control, significantly reduced VAS scores of weight-bearing pain versus baseline after 26 weeks of therapy in a well designed trial; however, there were no significant differences between the three treatment groups. Neither hyaluronic acid formulation had a longer duration of clinical benefit than the saline control. Supartz® was well tolerated in patients with osteoarthritis of the knee. An integrated analysis of the five, well designed clinical trials demonstrated no significant difference between the Supartz® or control groups in the incidence of adverse events. The most common adverse events reported in Supartz® recipients were arthralgia, arthropathy/arthrosis/arthritis, back pain, nonspecific pain, injection-site reaction, headache and injection-site pain.

Ocular Tolerance to a Topical Formulation of Hyaluronic Acid and Chitosan-Based Nanoparticles

Hyaluronic acid-chitosan nanoparticles (HA-CS NPs) have the potential to serve as a reliable drug delivery system to topically treat ocular surface disorders. We evaluated the in vivo uptake by ocular structures, the acute tolerance, and possible alterations of tear film physiology in rabbits. Fluorescent HA-CS NPs (fl-HA-CS NPs) were prepared by ionotropic gelation using fluoresceinamine-labeled hyaluronic acid and resuspended in buffer. fl-HA-CS NPs (30 microL, 0.5 mg/mL) and fluoresceinamine-HA conjugate (30 microL) were instilled into rabbit eyes every 30 minutes for 6 hours. In vivo uptake and acute tolerance were characterized 24 hours after the first instillation and compared with preinstillation measurements. Clinical signs, including tear production, lacrimal drainage system patency and reflux, and ocular surface pathology, were evaluated. The rabbits showed no signs of ocular discomfort or irritation after exposure to HA-CS NPs. No macroscopic alteration in ocular surface structures was observed. fl-HA-CS NPs were present inside conjunctival and corneal epithelial cells, although the distribution within the cells was different. The fl-HA-CS NPs had no significant effects on tissue morphology and functionality, tear production, or drainage. Taken together, these data demonstrate that HA-CS NPs are a safe drug carrier for ocular surface application.

Complex Fluids Based on Methacrylated Hyaluronic Acid

We present the preparation and characterization of viscoelastic formulations of hyaluronic acid functionalized with polymerizable methacrylate groups. We explored three different processing strategies for controlling microstructure and interchain interactions: lightly cross-linked near-gels, emulsion-cross-linked microspheres, and an elastic microgel formed through centrifuging the microspheres. The component structure and rheological properties of these formulations were compared to those of high molecular weight hyaluronic acid solutions, which displayed classical behavior of high molecular weight polymer solutions reported by other investigators. We demonstrate that these processing strategies allow the tuning of solution properties from strongly viscoelastic behavior, observed in lightly cross-linked near-gels and concentrated microsphere solutions to elastic behavior in elastic microgels, behaving like pseudoplastic liquids having a well-defined yield stress above which viscous behavior was observed. In the centrifuged microspheres, the hyaluronic acid degree of methacrylation was inversely proportional to the gel elasticity, and a mechanism based on failure due to microsphere brittleness is proposed to explain this behavior. These results suggest that processing methacrylated hyaluronic acid can lead to a diversity of solution properties, providing methods for delivering this biologically active polymer in a broad range of applications.

Large particle hyaluronic acid for the treatment of facial lipoatrophy in HIV‐positive patients: 3‐year follow‐up study

Facial lipoatrophy can be a stigmatizing side effect of antiretroviral (AVR) treatment for HIV-infected patients. We sought to evaluate the long-term efficacy and safety of a new formulation of hyaluronic acid that can be injected in larger amounts and into deeper skin layers during 3 years of follow-up. Twenty patients received injections of Restylane SubQ(). Refill treatment was offered at 12 and 24 months. Treatment effects were evaluated using ultrasound, the Global Aesthetic Improvement Scale, visual analogue scale (VAS) and the Rosenberg self-esteem scale. Seventeen patients remained at 36 months. Mean (+/- standard deviation) total cutaneous thickness increased from 6 +/- 1 mm at baseline to 12 +/- 1 mm (P<0.001) at 36 months. Response rate (total cutaneous thickness >10 mm) was 70%. Fifteen patients classified their facial appearance as very much or moderately improved. VAS increased from 39 +/- 25 to 70 +/- 20 (P<0.05) and higher self-esteem scores were reported. Local swelling and tenderness after treatment was common. Persistent papules found in several patients after treatment were removed effectively with hyaluronidase injections. Three patients, treated only at baseline, still had higher total cutaneous thickness scores at 36 months. Our results indicate that a large particle hyaluronic acid formulation is a durable and well-tolerated dermal filler for treating HIV-positive patients with facial lipoatrophy.

Acido ialuronico. Terapia di forma o di sostanza? Risultati ed evoluzione

Hyaluronic acid was identified about 70 years ago and has been used in the treatment of cartilage pathologies for 20 years. Laboratory studies show that hyaluronic acid, besides its lubricating or filling properties, has important metabolic actions essential for cartilage vitality. In recent years, thanks to bioengineering progresses, it became possible to obtain solid hyaluronic acid formulations useful for growth and differentiation of chondrocites and stem cells, thus creating new interesting therapeutic perspectives.

Volumizing effects of a smooth, highly cohesive, viscous 20-mg/mL hyaluronic acid volumizing filler: prospective European study

BackgroundFacial volume loss contributes significantly to facial aging. The 20-mg/mL hyaluronic acid (HA) formulation used in this study is a smooth, highly cohesive, viscous, fully reversible, volumizing filler indicated to restore facial volume. This first prospective study evaluated use in current aesthetic clinical practice.MethodsA pan-European evaluation conducted under guidelines of the World Association of Opinion and Marketing Research, the trial comprised a baseline visit (visit 1) and a follow-up (visit 2) at 14 ± 7 days posttreatment. Physicians photographed patients at each visit. Each patient was treated with the 20-mg/mL HA volumizing filler as supplied in standard packaging. Procedural details, aesthetic outcomes, safety, and physician and patient ratings of their experience were recorded.ResultsFifteen physicians and 70 patients (91% female; mean age: 50 years) participated. Mean volume loss at baseline was 3.7 (moderate) on the Facial Volume Loss Scale. Local anesthesia was used in 64.3% of cases. Most injections (85%) were administered with needles rather than cannulas. Of the 208 injections, 59% were in the malar region, primarily above the periosteum. Subcutaneous injections were most common for other sites. The mean total injection volume per patient was 4.6 mL. The mean volume loss score declined significantly (P < .001) to 2.1 at visit 2. On the Global Aesthetic Improvement Scale, 88% and 76% of the treatments were rated very much improved or much improved by physicians and patients, respectively. Of the physicians, 95.6% rated this HA filler as very or fairly easy to use. Similarly, 92% of patients were very likely or quite likely to return for treatment; nearly all (98%) would recommend this treatment to friends. Transient (mean duration: 5.5 days) injection-site adverse events (AEs) occurred in 24 patients. Bruising was the most common AE.ConclusionThe 20-mg/mL smooth, highly cohesive, viscous, volumizing HA filler was effective, well tolerated, and easy to use in current clinical practice. Participants were very likely to recommend this product to colleagues and friends, and patients would be very or quite likely to request this product for future treatments.

A Pilot Human Evaluation of a Formulation of Irinotecan and Hyaluronic Acid in 5-Fluorouracil-Refractory Metastatic Colorectal Cancer Patients

Background: Preclinical data demonstrate that the polysaccharide hyaluronic acid (HA) acts as a macromolecular carrier for chemotherapeutic drugs. In these studies the formulation of HA and irinotecan reduced treatment-related toxicity and improved efficacy via the preferential delivery of irinotecan to the tumor and lymph nodes. This study was designed as a first-in-man investigation of the safety and pharmacokinetics of irinotecan when administered within the HA-Irinotecan formulation. Methods: 5-Fluorouracil refractory metastatic colorectal cancer patients were intravenously treated with HA-Irinotecan (300 mg/m² irinotecan with 1,000 mg/m² HA) on day 1 of a 21-day cycle. After safety was demonstrated, the irinotecan dose was increased to 350 mg/m² with maintenance of the HA at 1,000 mg/m².DELETEResults: Twelve patients were treated with HA-Irinotecan. Overall toxicity was low, with an 8 and 17% incidence of grade lll/lV diarrhea and neutropenia, respectively. No grade III/IV nausea or vomiting was observed. Seventeen percent of patients had a partial response and 50% experienced stable disease, indicating that the efficacy of the irinotecan was maintained. Median survival was 16.6 months, while median progression-free survival was 6.2 months. Conclusion: HA-Irinotecan containing standard doses of irinotecan can be safely administered to patients. Comparison to historical irinotecan data suggests HA-Irinotecan may have a greater margin of safety without compromising anticancer activity.

116 Applicaton of a Novel Crosslinked Glycosaminoglycan Hydrogel Scaffold Improves Healing in a Rabbit Ear Ulcer Model

Introduction: Hyaluronic acid (HA) is a major glycosaminoglycan component of normal dermis and a major component of the matrix synthesized during wound healing. Previous studies have shown that uncrosslinked HA is rapidly degraded and cleared in vivo, limiting its clinical utility. We have used a novel HA hydrogel scaffold that is crosslinked for prolonged bioavailability. It has a porous interior and a smooth surface. This scaffold can also be fabricated with collagen and linked to proteins or DNA to direct cell growth and differentiation. We hypothesized that this novel HA formulation might itself improve wound healing by enhancing cell migration. Purpose: The present study explored the effects of a crosslinked HA hydrogel on wound healing. Methods: Using an established model of wound healing, four 7 mm punch wounds were made on each ear of New Zealand rabbits. Each wound was immediately treated with topical application of one of the following: HA hydrogel (n = 26), HA/collagen hydrogel (n = 27), or phosphate-buffered saline (PBS)(n = 16). Wounds were harvested on day 8 for histologic evaluation. Sections were examined for epithelial and granulation tissue ingrowth into wounds. Results: HA- and HA/collagen-treated wounds showed statistically significant increases in epithelial (p = 0.003 and p = 0.007, respectively) and granulation tissue ingrowth (p = 0.004 and p = 0.01, respectively) when compared to PBS-treated controls. Conclusions: In the rabbit ear ulcer model, the application of crosslinked HA and HA/collagen hydrogels accelerated wound healing as measured by epithelial and granulation tissue ingrowth. Funding Source: NIH grant: 5R01GM063825–03

Results of Endovesical Hyaluronic Acid/Chondroitin Sulfate in the Treatment of Interstitial Cystitis/Painful Bladder Syndrome

The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients. A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response. After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks' treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement. In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.

EFFECTS OF ENDOVESICAL HYALURONIC ACID/CHONDROITIN SULFATE IN THE TREATMENT OF INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME

Objectives- The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients. Methods- A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response. Results- After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement. Conclusions- In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.

AM‐111 Reduces Hearing Loss in a Guinea Pig Model of Acute Labyrinthitis

This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation. A controlled, prospective animal study using a guinea pig model of acute labyrinthitis. Acute labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 microL of AM-111 at concentrations of 100 micromol/L, 10 micromol/L, and 1 micromol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis. The ABR results on day 21 demonstrated that untreated control ears for acute labyrinthitis had a mean hearing loss (HL) of 68 +/- 12 dB. In contrast, ears treated with AM-111 (100 micromol/L) had a mean HL of 39 +/- 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls. AM-111 delivered over the round window membrane in a 100 microL hyaluronic acid formulation at a 100 micromol/L concentration immediately after induction of acute labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.

The haemocompatibility of polyurethane–hyaluronic acid copolymers

Despite decades of research into haemocompatible biomaterials, there remain surprisingly few materials that can be used in blood-contacting applications. We have synthesized copolymers of polyurethane (PU) with hyaluronic acid (HA) with the goal of creating materials that incorporate an inherently non-thrombogenic, biological component into the bulk polymer structure. HA was incorporated into the polymer backbone as a chain extender during PU synthesis, and the physical and biological properties of the resulting copolymer were directly controlled by the HA content. Increases in HA content led to a linear increase in hydrophilicity ( R 2=0.993) and corresponding increase in surface energy compared to PU controls. Elastic modulus also increased with HA content ( p<0.001), while surface roughness did not significantly differ from PU controls for most PU–HA formulations. Incorporation of HA resulted in negligible platelet adhesion to the PU–HA ( p<0.001), representing a 20-fold decrease in platelet adhesion compared to PU. Red blood cell adhesion also decreased with increasing HA content ( p<0.001). The PU–HA materials were cytocompatible and supported endothelial cell adhesion and viability. Thus, we have demonstrated the synthesis of a copolymer whose physical and biological properties are easily tailored, and whose potent anti-thrombogenic properties demonstrate its great promise for use in vascular applications.

Intraarticular Hyaluronic Acid Supplementation in the Horse: The Role of Molecular Weight

Abstract Osteoarthritis (OA) is a primary cause of lameness and loss of use in the equine industry. Treatment of affected joints is aimed at reducing synovial inflammation, halting the inflammatory cascade within the joint, minimizing articular cartilage breakdown, and reducing pain. Treatments of affected joints commonly used by equine practitioners include intraarticular hyaluronic acid (HA). Consideration of the average molecular weight (MW) and concentration of the HA product may dictate what product is selected. The purpose of this review is to briefly summarize for the practitioner the scientific data available evaluating the significance of hyaluronic acid molecular weight with regard to efficacy and duration of action in horses when administered intraarticularly. In summary, the beneficial effects of HA supplementation are attributable to the anti-inflammatory effects, improvement in viscoelastic properties of the synovial fluid, and interaction with the synovial membrane affecting pain transmission and joint metabolism. As this review shows, the importance of HA molecular weight with regard to efficacy of treating synovial inflammation and osteoarthritis has not been clearly demonstrated, and results are conflicting. Until there is a full understanding of the mechanism of action of HA within the joint, the veterinarian's choice of HA products will continue to be based on clinical preference. Additional studies directly comparing products of different HA average molecular weights and formulations in a controlled in vivo setting are needed to assess the importance of HA molecular weight in treating joint disease.

Viscosupplementation in the hip: evaluation of hyaluronic acid formulations

This study compares three different hyaluronate formulations and evaluates functionality, time of satisfactory pain relief and also the delay in performing a total hip arthroplasty. One hundred and twenty patients (126 hips) received viscosupplementation with one of the three hyaluronate formulations. All patients were candidate for surgical treatment with a total hip arthroplasty. Three different products were consecutively used: Adant®, Synocrom® or Synvisc®. Patients were assessed 6 weeks after each infiltration using Visual Analogue Scale and Harris Hip Score. The Harris Hip Score increased significantly in two of the three groups compared to baseline, but no statistical significant difference was noted between the groups. Viscosupplementation provides significant pain reduction in two of the three groups. There is no significant difference in duration of the effect of the first infiltration between the three groups. The positive effect was still ongoing at the end point of the study in 46 hips: 51% of the patients did not undergo total hip arthroplasty, 3 years after viscosupplementation.