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.

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.

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.

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.

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.

Characterization of the visco-elastic properties of hyaluronic acid.

BACKGROUND: Hyaluronic acid (HA) is a polysaccharide present in almost all animal tissues, in which it carries out important biological functions, among them, the protection of the joints by lubricating them and dampening the tension in them. OBJECTIVE: This study compares the viscoelastic properties of several commercial preparations of HA, to determine their suitability for use as viscosupplementation therapy in joint pathology (osteoarthritis). METHODS: 4 HA hydrogels: Durolane®, Synocrom_Forte_One®, Synvisc_One® and Viscoplus_Matrix® and 4 HA solutions: Ostenil®, Ostenil_Plus®, Viscoplus_Gel® and Orthovisc® were analyzed to compare their viscoelatsic rheological parameters using an oscillatory-rotational rheometer. RESULTS: With respect to the 4 HA hydrogels, comparison of crossover frequencies allowed division into two main groups: Synvisc_One® and Viscoplus_Matrix®, with crossover frequencies in the order of magnitude of 10-2 Hz, while Synocrom_Forte_One® and Durolane® showed crossover frequencies on the order of 10-1 Hz. Only one of the 4 HA solutions, Viscoplus_Gel®, showed a crossover frequency on the order of 10-2, whereas Ostenil_Plus® and Orthovisc® showed crossover frequencies on the order of 10-1, and Ostenil® remained as a predominantly viscous fluid for frequencies as high as 4.8 Hz. CONCLUSIONS: The viscoelastic properties of the HA preparations can be ordered according to the values of G∗ (the rigidity, or vector sum of the elastic modulus G' and the viscous modulus G'') at both transition points (0.5 and 2.5 Hz) as follows: Viscoplus_Matrix®  > Viscoplus_Gel®  > Durolane®  > Synocrom_Forte_One®  > Ostenil_Plus®  > Synvisc_One®  > Orthovisc®  > Ostenil®.

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.

Enhancement of chondrogenesis of adipose-derived stem cells in HA-PNIPAAm-CL hydrogel for cartilage regeneration in rabbits.

Injectable thermoresponsive hydrogels have the advantages of effective cell delivery and minimal invasion for tissue engineering applications. In this study, we investigated the chondroinductive potential of newly developed hyaluronic acid (HA)-modified thermoresponsive poly(N-isopropylacrylamide) (HA-PNIPAAm-CL) hydrogels on enhancing rabbit ADSC (rADSC) chondrogenesis in vitro and in the synovial cavity of rabbit. The HA-mixed PNIPAAm (HA-PNIPAAm-CP) and HA-cross-linked PNIPAAm (HA-PNIPAAm-CL) were fabricated using physical interaction and chemical cross-linking methods, respectively. The in vitro results showed that, compared to unmodified PNIPAAm, both HA-modified hydrogels significantly increased cell viability, chondrogenic marker gene (aggrecan and type II collagen) expression and sulfide glycosaminoglycan (sGAG) formation in embedded rADSCs. However, HA-PNIPAAm-CL showed the highest rADSC viability and chondrogenesis. The chondrogenic effects of HA-modified hydrogels on rADSCs were confirmed in vivo by the intraarticular injection of hydrogel-embedded rADSC constructs into rabbit synovial cavities for 3 weeks and tracing with CM-DiI labeling. Neocartilage formation in the hydrogels was determined by histomorphological staining of GAG and type II collagen. In vivo injected rADSC/HA-PNIPAAm-CL constructs showed more hyaline cartilage formation than that of rADSC/HA-PNIPAAm-CP and rADSC/PNIPAAm constructs in the synovial cavity of rabbit. These results suggest that the HA-PNIPAAm-CL provides a suitable microenvironment to enhance ADSC chondrogenesis for articular cartilage tissue engineering applications.

Injectable liquid polymers extend the delivery of corticosteroids for the treatment of osteoarthritis.

Drug delivery strategies generally use inert materials, such as high molecular weight polymers, to encapsulate and control the release rate of therapeutic drugs. Diffusion governs release and depends on the ease of permeation of the polymer alongside the device thickness. Yet in applications such as osteoarthritis, the physiological constraints and limited intra-articular joint space prevent the use of large, solid drug delivery implants. Other investigators have explored the use of micro- and nanoparticle drug delivery systems. However, the small size of the systems limits the total drug that may be encapsulated and its short diffusion distance causes rapid release. Ordinarily, the extremely low diffusivity of a polymer fluid would make this an unsuitable delivery system. Our technology takes advantage of specific molecular interactions between drug and polymer, which can control the rate of release beyond diffusion. With this "affinity-based drug delivery", we have shown that delivery rates from solid polymer can be prolonged from hours and days, to weeks and months. In this paper, we demonstrate that this affinity-based mechanism also applies to low diffusivity fluid-phase polymers. They show release rates that are substantially slower than chemically similar polymers incapable of forming those inclusion complexes. The similarity of this study's liquid polymers to the viscoelastic fluids used in current clinical practice makes it an ample delivery system for osteoarthritic application. We confirmed the capacity of anti-inflammatory delivery of corticosteroids: hydrocortisone, triamcinolone, and dexamethasone; from both solid implants and polymer fluids. Further, we demonstrated that viscoelastic properties are widely tunable, and within the range of native synovial fluid. Lastly, we determined these polymer fluids have no impact on the differentiation of mesenchymal stem cells to cartilage and are not cytotoxic to a common cell line.

A Comparison Between Rheological Properties of Intra-articular Hyaluronic Acid Preparations and Reported Human Synovial Fluid.

INTRODUCTION: This study aims to compare the properties of currently available intra-articular hyaluronate (IA-HA) products widely available in the USA to those of healthy knee synovial fluid with respect to their bulk rheological properties. We hypothesize that products would have differing rheological properties, with some more closely resembling the properties and physiological aspects of healthy joint fluid HA. METHODS: We obtained reported HA product molecular weights, as well as measurements of the presence of cross-linking, zero shear rate viscosity, shear thinning ratio, and crossover frequency for the following IA-HA products available in the USA: Euflexxa®, Orthovisc®, Supartz®, Monovisc®, Synvisc®, Synvisc-One®, Gel-One®, and Hyalgan®. RESULTS: Differences were seen between the study products across all of the investigated parameters. Hyalgan, Supartz, Orthovisc, and Euflexxa had a linear chain structure, while Synvisc, Synvisc-One, and Monovisc were cross-linked in structure. Molecular weight, shear rates, and crossover frequencies ranged widely across tested products, with values ranging from below to above those reported for healthy knee synovial fluid HA. When compared to healthy knee parameter values reported within the current literature, observed parameters for Euflexxa and Orthovisc were typically seen to be the most similar to healthy knee synovial fluid. When comparing Euflexxa and Orthovisc directly, Euflexxa was more often similar to the properties of healthy knee synovial fluid with respect to the observed parameters of molecular structure, shear rates, and crossover frequency. CONCLUSION: Available IA-HA products vary with respect to molecular weight, presence of cross-linking, shear rate dependency of viscosity, and crossover frequency. Since IA-HA treatment for osteoarthritis aims to restore synovial fluid back to original HA property characteristics, using HA supplements resembling healthy synovial fluid is a logical approach. Our findings demonstrate that Euflexxa is the most similar to healthy synovial fluid with respect to molecular structure, shear rates, and crossover frequency. FUNDING: Ferring Pharmaceuticals, Inc.

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.

Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee.

BACKGROUND: Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee. PURPOSE: To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA. STUDY DESIGN: Meta-analysis. METHODS: A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics. RESULTS: A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight <3000 kDa. Products with a molecular weight ≥3000 kDa demonstrated significantly fewer discontinuations due to treatment-related adverse events than did ≤1500 kDa counterparts, while trial discontinuation rates were similar between biological fermentation-derived HA products and avian-derived HA. The results did not demonstrate a significant difference in the occurrence of effusion across molecular weight subgroups. Additionally, biological fermentation-derived HA had a significantly smaller incidence of effusion than did avian-derived HA. Biological fermentation-derived HA demonstrated fewer acute flare-ups at the injection site than did avian-derived HA products, while high-molecular-weight products demonstrated the highest rate of injection site flare-up. CONCLUSION: Despite similarities, IA-HA products should not be treated as a group, as there are differences in IA-HA products that influence both efficacy and safety. In the available literature, IA-HA products with a molecular weight ≥3000 kDa and those derived from biological fermentation relate to superior efficacy and safety-factors that may influence selection an IA-HA product for OA of the knee.

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.

Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model.

Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra-articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation. ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used. In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by µCT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA-reacetylated chitosan hydrogel surprisingly led to increased subchondral bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies toward more effective viscosupplementation formulations.

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.

Assessment of intraoperative complications in intumescent cataract surgery using 2 ophthalmic viscosurgical devices and trypan blue staining.

PURPOSE: To evaluate intraoperative complications during capsulorhexis and phacoemulsification in intumescent white cataracts using 2 ophthalmic viscosurgical device (OVD) techniques. SETTING: Ruhr University Eye Clinic, Bochum, Germany. DESIGN: Case series. METHODS: Patients with eyes with intumescent white cataract were recruited and placed in 2 groups. After capsule staining using trypan blue, a central indentation of the anterior lens capsule was created in the eyes in Group 1 using a medium-viscosity OVD (Healon 1.0%) and in the eyes in Group 2 using both medium-viscosity (1.0%) and high-viscosity (2.3%) OVDs. Then a continuous curvilinear capsulorhexis (CCC) was performed. The outcomes measured were the horizontal and vertical diameters of the CCC, the deviation from the target diameter, and intraoperative complications. RESULTS: In Group 1 (21 eyes), deviation from the target CCC diameter occurred in 12 eyes (10 oversized, 2 undersized), and in Group 2 (20 eyes) deviation occurred in 6 eyes (4 oversized, 2 undersized). In Group 1, capsule tears appeared in 2 eyes and in 1 eye, the procedure had to be converted to extracapsular cataract extraction with anterior vitrectomy. In Group 2, there were no capsule tears. CONCLUSION: Using 2 different OVDs and placing the high-viscosity OVD centrally led to safe indentation of the anterior lens capsule and reduced the risk for CCC enlargement and capsule tear during surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.