Novel vitreous substitutes: the next frontier in vitreoretinal surgery.

PURPOSE OF REVIEW: After removing the native vitreous during vitreoretinal surgery, an adequate substitute is required to ensure homeostasis of the eye. Current clinically used endotamponades (silicone oil, gases, semifluorinated alkanes) are effective in promoting retinal reattachment, but lead to complications such as emulsification, prolonged inflammation, blurred vision, raised intraocular pressure, cataract formation or the need for revision surgery. The aim of this review is to provide an update on novel vitreous substitutes with a focus on polymer-based systems. RECENT FINDINGS: Polymeric hydrogels provide favourable properties such as high water content, optical transparency, suitable refractive indices and densities, adjustable rheological properties, injectability, biocompatibility and their ability to tamponade the retina via viscosity and swelling pressure, comparable to the native human vitreous body. Here, vitreous replacement strategies can be divided into chemically or physically crosslinked hydrogel systems that are applied as preformed or in-situ gelling matrices. SUMMARY: Several hydrogel-based vitreous substitutes have already been positively evaluated in preclinical tests and have the potential to enter the clinical phase soon.

The effectiveness of high molecular weight hyaluronic acid for knee osteoarthritis in patients in the working age: a randomised controlled trial.

BACKGROUND: High molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated. METHODS: In this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient's global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed. RESULTS: In total, 156 subjects were included (intervention group 77, control group 79). Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2% (p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest (δ 0.8, 95%CI 0.2; 1.4, p = 0.010), knee related function (δ - 6.8, 95%CI -11.9; - 1.7, p = 0.010) and PGA (δ - 0.7, 95%CI -0.9; - 0.4, p < 0.0001). CONCLUSIONS: Intra-articular HMW-HA added to usual care is effective for knee OA in patients in the working age. TRIAL REGISTRATION: www.trialregister.nl , NTR1651, registered 2009-3-3.

Rheological Properties of Several Hyaluronic Acid-Based Gels: A Comparative Study.

BACKGROUND: Adding lidocaine to hyaluronic acid (HA)-based gels appeared to modify their rheological properties, in the view of the first author. OBJECTIVE: This paper sought to compare the rheological properties of three CE-marked and FDA-approved gels, administered with and without lidocaine, along with two other newly FDA-approved gels. METHODS: The tested gels were as follows: NASHA® Restylane® with and without lidocaine; CPM®; Belotero® Balance with and without lidocaine; 3-D Matrix®; Surgiderm® 30XP (without lidocaine) and Juvederm® Ultra 3- Juvederm® Ultra Plus XC (with lidocaine); Preserved Network® RHA®2 (with lidocaine); Vycross® Volbella® (with lidocaine). For rheological analyses, viscoelastic data were collected with plate-plate geometry of 25mm, temperature regulated by a Peltier-effect plate, and the following assessed: Strain sweep from 0.01% to 3000% strain at 1Hz over frequency sweep from 0.1 to 100 Hz. RESULTS: NASHA Restylane gels with and without lidocaine exhibited similar viscoelastic characteristics, with very similar tan δ values, but the elastic modulus G' proved significantly higher when the gel was injected with lidocaine vs without. 3D-Matrix Surgiderm 30XP gel without lidocaine and Juvéderm Ultra 3 with lidocaine exhibited similar viscoelastic characteristics, as well as tan δ values, yet the elastic modulus G' of Surgiderm 30XP proved significantly higher than that of Juvederm Ultra 3-Juvederm Ultra Plus XC. CPM Belotero Balance gels with and without lidocaine exhibited similar G' and G'' values. tan δ was somewhat higher when the gel was administered without lidocaine. VYCROSS Volbella gel exhibited a higher elastic modulus G' than the other Allergan gels, roughly nearing the NASHA gel values. Preserved Network RHA 2 gel exhibited values that were close to its partially cohesive "competitors", except for Vycross. CONCLUSION: Adding lidocaine to HA gels does modify their rheological properties yet this, to a variable extent depending on the product. J Drugs Dermatol. 2018;17(9):948-954.

Can hybrid hyaluronic acid represent a valid approach to treat rizoarthrosis? A retrospective comparative study.

BACKGROUND: Osteoarthritis (OA) of the trapeziometacarpal joint (TMJ) is a disabling condition with a significant impact on quality of life. The optimal management of hand OA requires a combination of non-pharmacological and pharmacological treatments that include intra-articular (i.a.) therapy. EULAR experts recommend corticosteroid injections in TMJ OA and underline the usefulness of hyaluronic acid (HA). The aim of this study was the assessment of the efficacy and tolerability of i.a. injections of a hybrid formulation of HA (Sinovial H-L®) in comparison to triamcinolone in patients with TMJ OA. METHODS: This 6-months observational comparative study, retrospective analyzed the medical records of 100 patients with monolateral or bilateral TMJ OA, treated with two injections of Sinovial H-L® (Sinovial H-L Group) or of triamcinolone acetonide (Triamcinolone Group). Clinical assessments were recorded at the time of the first and second injection and after one, 3 and 6 months. The primary outcomes were the change in global pain on a Visual Analogue Scale (VAS) and in hand function evaluated by the Functional Index for Hand OA (FIHOA) from baseline to month 6. Secondary outcomes were the improvement of the duration of morning stiffness, Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short Form (SF-36). The comparison between the two groups of treatment were performed with the Wilcoxon rank-sum test for continuous variables and with chi-square or Fisher exact test for categorical variables. Statistical significance was set at p < 0.05. RESULTS: Both therapies provided effective pain relief and joint function improvement, but the benefits achieved were statistically significantly superior in the Sinovial H-L Group than the Triamcinolone Group after one month (p < 0.01) from the beginning of the therapy and during the 6-months follow-up (p < 0.001). Furthermore, Sinovial H-L® was associated with a significant decrease in the duration of morning stiffness and with a significant improvement in the HAQ score and physical component summary (PCS)-SF-36. CONCLUSIONS: Our results suggested that the hybrid formulation of HA may be more effective than triamcinolone in pain relief and joint function improvement with a rapid and persistent effect, resulting a valid alternative to steroid in the management of TMJ OA. TRIAL REGISTRATION: ClinicalTrials.gov, date of registration: June 14, 2017, NCT03200886 . The present trial was retrospectively registered.

Rheological Properties and In Vivo Performance Characteristics of Soft Tissue Fillers.

BACKGROUND: Physicochemical properties and performance in nonclinical animal models can provide insights into soft tissue filler performance. OBJECTIVE: To evaluate the in vivo performance of fillers with different compositions and physicochemical properties. MATERIALS AND METHODS: Physicochemical properties were measured in vitro. Rat models were developed and used to compare lift capacity, resistance to deformation, and tissue integration. Four homogeneous hyaluronic acid (HA) fillers, 2 nonanimal stabilized HA (NASHA) fillers, and 1 calcium hydroxylapatite/carboxymethyl cellulose (CaHA/CMC) filler were evaluated. RESULTS: Filler lift capacity correlated better with filler composition/type (homogeneous > NASHA > CaHA/CMC) than with specific rheological properties. The CaHA/CMC filler had high initial resistance to deformation relative to other groups; all HA fillers exhibited lower initial resistance to deformation, which increased over time. Homogeneous HA fillers were integrated with surrounding tissue, whereas integration within particle-based fillers (NASHA and CaHA/CMC) was variable, with some areas void of tissue. CONCLUSION: The animal models provide a platform to make comparative evaluations among fillers. The results indicated that biological interaction plays an important role in how the filler performs. Rheology alone was not sufficient to understand filler performance but was most useful when comparing within fillers of similar composition.

Optimal Viscosity and Particle Shape of Hyaluronic Acid Filler as a Scaffold for Human Fibroblasts.

The authors previously reported that cultured human fibroblasts suspended in a hyaluronic acid filler can produce human dermal matrices with extended in vivo stability in animal and clinical studies. The present study was undertaken to determine the optimal viscosity and particle shape of hyaluronic acid filler as a scaffold for cultured human dermal fibroblasts to enhance the maximal viability of injected cells. The fibroblasts were suspended in either 1 of 3 hyaluronic acid viscosities at 2 different particle shapes. The viscosities used in this study were low (600,000-800,000 centipoises), moderate (2,000,000-4,000,000 centipoises), and high (8,000,000-12,000,000 centipoises). The particle shape was evaluated by testing round and irregular shapes. The fibroblast mixed bioimplants were injected into the back of individual athymic nude mice. The levels of type I collagen were measured using fluorescent-activated cell sorting (FACS) and immunohistochemical staining at 16 weeks after the injections. Results of FACS demonstrated that the mean cell ratio with human collagens in the moderate viscosity group was greater than those of control, low, and high viscosity groups. An immunohistochemical study showed similar results. The moderate viscosity group demonstrated the highest positive staining of human collagens. However, there were no significant differences between groups of irregular and round shape particles. A hyaluronic acid bioimplant with moderate viscosity is superior to that with low or high viscosity in the viability for human fibroblasts. However, the particle shape does not influence the viability of the fibroblasts.

Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model.

OBJECTIVES: We hypothesized that high-molecular-weight (MW) cross-linked (CL) hyaluronic acid (HA) improves joint lubrication and has an enhanced chondroprotective effect. We examined the histopathological changes and friction coefficients in osteoarthritic knee joints after injecting high-MW CL HA. DESIGN: A bilateral anterior cruciate ligament transection (ACLT) model in 20 Japanese white rabbits was used. From week 5 after transection, low-MW HA (0.8 × 10(6) Da; HA80) or high-MW CL HA (6 × 10(6) Da; HA600) was injected weekly into 10 right knee for 3 weeks; normal saline (NS) was injected into the 10 left knee. A sham operation was undertaken to exclude spontaneous osteoarthritis (OA) in five knees. Results were evaluated with macroscopy, histopathology (Kikuchi's score), biomechanical testing, and rheological assessment of the joint fluid viscoelasticity. Statistical analysis was performed using one-way analysis of variance with a 95% confidence interval (CI) (P < 0.05). RESULTS: The macroscopic findings showed severely damaged cartilage in 30% of the NS group and 20% of the HA80 and HA600 groups and intact cartilage in 100% of the sham group. The histological scores and friction coefficients of the HA600 group were significantly lower than those of the NS group (P = 0.007 and P = 0.002, respectively). Viscoelasticity measurements of the joint fluid showed no significant differences between the three treatment groups. CONCLUSION: High-MW CL HA exerts potential chondroprotective effects and produces superior friction coefficients. Our results suggest that HA600 delays the progression of OA effectively and improves joint lubrication significantly.

Comparative studies of hyaluronan in marketed ophthalmic products.

PURPOSE: Research has indicated that there is a correlation between the molecular weight of hyaluronan or hyaluronic acid (HA) and its biocompatibility/biological functions with high molecular weight HA showing many biological benefits. The purpose of this research was to characterize and compare the molecular weights, molecular weight distributions, and concentrations of HA present in a series of commercially available HA-containing ophthalmic products. METHODS: On-line size-exclusion chromatography with triple detection (SEC-TD) was used to determine the molecular weights and concentration of HA in commercially available products, including marketed contact lens multipurpose solutions and contact lens packaging solutions. Eleven commercially available HA-containing ophthalmic products were characterized by SEC-TD. RESULTS: The weight-average molecular weights of the products tested ranged from 155,000 Daltons (Da) to 1,400,000 Da, the number-average molecular weight of the products ranged from 99,000 to 927,000 Da, and the concentration of HA ranged from 0.003 to 0.15%. CONCLUSIONS: A wide range of HA molecular weights and concentrations were found in the 11 ophthalmic products characterized in the present study. This study is the first reported to characterize HA molecular weights and concentrations in various marketed HA-containing ophthalmic products. Future investigation of the effect of low molecular weight HA on eye is required.

Does the Tyndall effect describe the blue hue periodically observed in subdermal hyaluronic acid gel placement?

BACKGROUND: The blue hue of skin overlying injected hyaluronic acid (HA) fillers in certain cases has been hypothesized in the literature as related to the Tyndall effect. This investigation aims to understand the relevant optical concepts and to discuss the plausibility of this assertion. METHODS: Theoretic and physical aspects of relevant optical theories including the Tyndall effect, the Raleigh criterion and the Mie Solution are discussed, with simple examples. The physical properties of the system (both HA and subcutaneous tissue) are explored. Alternate concepts of dermal hue generation are discussed. RESULTS: The Tyndall effect (and Rayleigh criterion) describe optical phenomenon that occur as light passes through colloidal solutions containing uniform spherical particles of sizes less than the length of a wavelength of visible light. HA fillers are complex, large, non-spherical, cross-linked hydrogels, and thus are not well characterized by these theories.Skin is a complex optical surface in which shorter wavelengths of light are selectively filtered at superficial depths. Light passing through to subdermal HA would have low blue light amplitude, minimizing what light could be preferentially scattered. Further, should blue hues be 'generated' subdermally, the same skin filters work in reverse, making the blue light poorly detectable by an external observer. CONCLUSIONS: The Tyndall effect is unlikely to cause dermal hue changes in HA filler instillation. Optical and perceptual processes explaining superficial vein coloration may better describe subdermal HA hue changes. Vein coloration is thought to be related to three processes: the reflective properties of the skin, the absorptive properties of blood and the perceptive properties of an observer's eyes. Subdermal HA may simulate these phenomena by a number of undetermined, yet plausible mechanisms.

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.

Hyaluronic acid nanoparticles titrate the viscoelastic properties of viscosupplements.

Hyaluronic acid (HA) is a glycosaminoglycan with diverse biomedical applications including viscosupplementation of synovial fluid for the treatment osteoarthritis. Current HA viscosupplements such as Synvisc, Orthovisc, and Hyalgan have shown positive effects of reducing pain and improving joint function. The therapeutic efficacy, however, is highly transient, and these viscous fluids suffer from poor injectability. HA nanoparticles were found to modify the rheological properties of a model of the HA viscosupplement Orthovisc. Nanoparticles were successfully synthesized from 17 and 1500 kDa HA. Nanoparticle suspensions of HA were studied at different concentrations and in blends with the model viscosupplement. Nanoparticles made from 1500 kDa HA reduced the viscosupplement viscosity and elasticity to a much greater degree than nanoparticles made from 17 kDa HA. The difference in the nanoparticle effect on viscoelasticity suggested that nanoparticles made from 17 kDa HA may have dangling surface polymers that facilitated interactions with HA in solution. This hypothesis was supported by the greater compressibility of 17 kDa nanoparticles as determined by ultrasonic vibrational spectroscopy. Rheological investigations showed that the viscoelasticity of viscosupplements could be discretely titrated by modulating the concentration and type of HA nanoparticle additive (hard sphere or hairy). Thus, the injectability of viscosupplements may be enhanced while maintaining high elasticity.

Systematic review of clinical trials of small- and large-gel-particle hyaluronic acid injectable fillers for aesthetic soft tissue augmentation.

BACKGROUND: Hyaluronic acid (HA) is the most frequently injected filler for soft tissue augmentation in the United States. OBJECTIVE: To systematically review published evidence for aesthetic use of small- and large-gel-particle HA. METHODS AND MATERIALS: Clinical data on anatomic area, level of evidence, patient population, trial design, endpoints, efficacy, and safety were extracted from PubMed. RESULTS: Fifty-three primary clinical reports were analyzed. The highest-quality efficacy evidence was for the nasolabial folds (NLFs), with 10 randomized, blind, split-face, comparative trials. Several randomized, blind trials supported treatment of the glabella, lips, and hands. Lower-level evidence (from studies with nonrandomized, open-label, or retrospective designs) was recorded for the nasojugal folds (tear troughs), upper eyelids, nose, infraorbital hollows, oral commissures, marionette lines, perioral rhytides, temples, and cheeks. Common adverse events (AEs) across anatomic areas were pain, bruising, swelling, and redness. Serious AEs were uncommon (8 events in 8 patients of 4,605 total patients) and were considered to be unrelated (7 events) or probably unrelated (1 event) to treatment. CONCLUSION: The efficacy and safety of small- and large-gel-particle HA are well established for NLFs; evidence for the glabella, lips, and hands is more limited. Preliminary reports in other anatomic regions suggest efficacy without major complications.

Experimental measure of retinal impact force resulting from intraocular foreign body dropped onto retina through media of differing viscosity.

BACKGROUND: To evaluate and compare the perfluorocarbon liquid, silicone oil, and viscoelastic against standard saline, in their ability to dampen the impact force of a foreign body, dropped within the eye. In an experimental surgical model in where cohesive and adhesive forces of the substances are not enough to float heavy-than-water foreign bodies. METHODS: A model of ophthalmic surgery was constructed. A BB pellet was dropped from 24 mm onto a force transducer through four different fluids: balanced salt solution, perfluoro-n-octane, viscoelastic, and silicone oil. The impact energy (force) for each case was measured and recorded by the force transducer. The mean force of impact for each fluid was compared using the Student t-test. RESULTS: Silicone oil resulted in the lowest force of impact. Both silicone oil and viscoelastic dampened the impact an order of magnitude more than perfluoro-n-octane and balanced salt solution. CONCLUSIONS: Silicone oil and viscoelastic cushioned the force from a dropped BB. They may be useful adjuncts to prevent iatrogenic retinal injury during vitrectomy for intraocular foreign body removal.

A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis.

OBJECTIVES: To compare the effects of an intermediate molecular weight (MW) intra-articular hyaluronic acid (HA) with a low MW product on knee osteoarthritis (OA) symptoms. METHODS: Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800-1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500-730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0-100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates RESULTS: The intention-to-treat (ITT) and per-protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5±1.0(SE) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO-ON, satisfying the claim for non-inferiority (lower limit>-9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated. CONCLUSIONS: Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety.

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

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

Gellan gum modified hyaluronic acid hydrogels as viscosupplements with lubrication maintenance and enzymatic resistance.

Osteoarthritis (OA) is a common disease caused by damage to articular cartilage and underlying bone tissues. Early OA can be treated by intra-articular injection of viscosupplements to restore the lost viscoelasticity and lubricity of synovial fluid. Hyaluronic acid (HA), as a most standard synovial fluid supplementation, can be easily degraded in vivo, bringing about lower viscoelasticity and increased injection frequency. In this study, we focus on products with reasonable viscoelasticity and long-lasting action time and develop a kind of polysaccharide-based hydrogel viscosupplement (HEG) based on HA chemically modified gellan gum (GG), which can maintain stable viscoelasticity with hyaluronidase for 1 week owing to the fact that the main component of GG still maintains a stable three-dimensional network structure after enzyme treatment. The as-developed injectable HEG hydrogel possesses good biocompatibility, excellent injectability, suitable viscoelasticity, satisfactory lubricity, and enzymatic resistance, demonstrating great potential to intervene in the development of OA.

Influence of hyaluronic acid on bacterial and fungal species, including clinically relevant opportunistic pathogens.

Hyaluronic acid (HA) has several clinical applications (aesthetic surgery, dermatology, orthopaedics and ophtalmology). Following recent evidence, suggesting antimicrobial and antiviral properties for HA, we investigated its effects on 15 ATCC strains, representative of clinically relevant bacterial and fungal species. The in vitro system employed allowed to assess optical density of broth cultures as a measure of microbial load in a time-dependent manner. The results showed that different microbial species and, sometimes, different strains belonging to the same species, are differently affected by HA. In particular, staphylococci, enterococci, Streptococcus mutans, two Escherichia coli strains, Pseudomonas aeruginosa, Candida glabrata and C. parapsilosis displayed a HA dose-dependent growth inhibition; no HA effects were detected in E. coli ATCC 13768 and C. albicans; S. sanguinis was favoured by the highest HA dose. Therefore, the influence of HA on bacteria and fungi warrants further studies aimed at better establishing its relevance in clinical applications.

Novel hyaluronic acid dermal filler: dermal gel extra physical properties and clinical outcomes.

BACKGROUND: Dermal gel extra (DGE) is a new, tightly cross-linked hyaluronic acid (HA)-based dermal filler containing lidocaine engineered to resist gel deformation and degradation. OBJECTIVES: To develop a firmer gel product (DGE) and compare the efficacy and safety of DGE with nonanimal stabilized HA (NASHA) for correction of nasolabial folds (NLFs). METHODS: DGE physical properties were characterized, and 140 subjects with moderate to deep NLFs were treated with DGE and NASHA in a randomized, multicenter, split-face design study. Efficacy, pain, and satisfaction were measured using appropriate standard instruments. Adverse events were monitored throughout the study. RESULTS: DGE has a higher modulus and a higher gel:fluid ratio than other HA fillers. Similar optimal correction was observed with DGE and NASHA through 36 weeks (9 months). Study subjects required less volume (p<.001) and fewer touch-ups (p=.005) and reported less injection pain (p<.001) with DGE treatment. Most adverse events were mild to moderate skin reactions. CONCLUSIONS: DGE is a firm HA gel that required significantly less volume and fewer touch-ups to provide equivalent efficacy to NASHA for NLF correction; both dermal gels were well tolerated. DGE will provide a comfortable and cost-effective dermal filler option for clinicians and patients.

A hydrogel system based on a lactose-modified chitosan for viscosupplementation in osteoarthritis.

Osteoarthritis (OA) is a chronic disease affecting joint functionality and often managed with hyaluronic acid (HA) administration. In this study, a hydrogel based on a lactose-modified chitosan (CTL) reticulated with boric acid has been developed as a viscosupplement for OA treatment. The rheological characterization allowed to identify a composition whose properties were in line with those of commercial products (in the order of tens of Pascal). The selected CTL-hydrogel showed biocompatibility and antioxidant activity in vitro, and it did not influence cytokines release by macrophages. Degradation studies carried out over 24 h pointed out its higher resistance to chemical degradation with respect to HA samples. Overall, this study underlines the advantages of the CTL-hydrogel to address the treatment of OA and shed light on an innovative application of CTL polymer, which is one of the main component of the proposed hydrogel system and not used in mixture with other molecules.

[Hyaluronic acid injection]. / Injection d'acide hyaluronique.

Hyaluronic acid is currently the leading product for the treatment of wrinkles. The side effects are few compared to the number of patients treated. Hyaluronic acid gives security and efficiency to the patient, which is important foe cosmetic indication.