Hyaluronic Acid Solution Research Articles

Efficacy of Intra-Articular Ozone Versus Hyaluronic Acid In Patients of Knee Osteoarthritis

Objective: To determine the analgesic efficacy of ozone gas versus hyaluronic acid solution in knee osteoarthritis patients. Study Design: Quasi-experimental study. Place and duration of study: Department of Pain Medicine, Combined Military Hospital, Rawalpindi Pakistan, from Jun to Dec 2020. Methodology: Seventy patients suffering from knee osteoarthritis fulfilling the inclusion criteria were included in this study and were randomly assigned to two equal groups to undergo intra-articular knee injection using either Hyaluronic Acid (Group-H) or Ozone (Group-O). Improvement in the numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale were recorded 1, 3 and 6 months after the procedure. Results: In both groups, the pain score (Group-H Pre-procedure NRS =7.66±0.87 vs. Post-Procedure 6 month NRS = 4.74±0.70, Group-O Pre-procedure NRS = 7.86±0.88 vs. Post-Procedure 6 month NRS = 4.46±0.92) and WOMAC (Group-H Pre-procedure =77.60±7.93 vs. Post-Procedure 6 month =40.31±6.81, Group-O Pre-procedure=75.54±9.40 vs. Post-Procedure 6 month =38.37±8.98) score improved. However, the NRS pain score (p-value = 0.21) and patient WOMAC score (p-value = 0.31) were not significantly different between groups. Conclusion: Neither Hyaluronic Acid nor Ozone appears superior in decreasing pain scores or physical limitations, particularly for knee osteoarthritis.

Pharmacologic activity of mGLUR4 agonist in a model of primary open-angle glaucoma: A preclinical experimental study

Background. Worldwide, more than 67 million people suffer from glaucoma. In Russia, this number exceeds 1.08 million people. Annually, the number of primary cases increases by 3–4%. The increasing prevalence of glaucoma intensifies the search for neuroprotectants that can reduce the loss of retinal ganglion cells, thereby impeding the progression of the disease. Objective. To study of the pharmacological activity of mGLUR4 agonist, ZC64-0001 substance, on a model of primary open-angle glaucoma. Methods. The conducted preclinical study involved 60 sexually mature male Wistar rats, weighing 180–220 g. The observation period was 73 days. The animals were divided into 6 groups with 10 animals in each. Group 1 included intact animals (without any manipulations); Group 2 included negative control animals with the water injected in the anterior chamber of the eye; in Group 3–6, primary open-angle glaucoma was modelled by injecting 1% hyaluronic acid solution into the anterior chamber of the eye once every 7 days from day 1 to day 62 of the study. Animals in Group 4 were treated intragastrically with H-[(4-chlorophenyl)methyl]-1,6-dihydro-4-methoxy-1-(2-methylphenyl)-6-oxo-3-pyridazinecarboxamide under the laboratory code of ZC64-0001 at a dose of 10 mg/kg. Animals in Group 5 received Mexidol as a comparison drug intramuscularly at a dose of 25.7 mg/kg. Animals in Group 6 were treated with a Timolol instillation at a dose of 0.009 ml/kg. The studied compounds were administered from day 63 of the study once a day for 10 days. The evaluated indicators included the level of microcirculation in the retina, the amplitude of a-wave and b-wave of the electroretinogram, and the number of retinal ganglionic layer nuclei in the setting of the conducted treatment. Statistical processing of the data was performed using the Statistica 10.0 software (StatSoft, USA). Differences were determined at the significance level of p ˂ 0.05. Results. ZC64-0001 increased the level of microcirculation relative to the group with modelled glaucoma by 11.5%, with this indicator being statistically significantly different from that both in the group with modelled glaucoma and the intact group ( р < 0.05). In the group of animals receiving ZC64-0001, the amplitude of a-wave increased relative to the primary glaucoma group by 17.7%, with this index being statistically different from the groups of intact animals and negative control (р < 0.05). The b-wave amplitude increased by 34.4% relative to the group with modelled glaucoma, being statistically different from the intact group, negative control group, pathology modelled group, and comparison drug groups ( р < 0.05). Administration of ZC64-0001 increased the number of retinal ganglion cell nuclei relative to the group with modelled glaucoma by 41.0%, which had a statistically significant difference from all the studied groups ( р < 0.05). Conclusion. The ZC64-0001 compound demonstrated high neuroprotective properties in a model of primary open-angle glaucoma, leading to an improvement in retinal microcirculation, an increase in the wave amplitude according to the conducted electrophysiological study, and an increase in the number of ganglion cell nuclei.

Antiadhesive Hyaluronic Acid-Based Wound Dressings Promote Wound Healing by Preventing Re-Injury: An In Vivo Investigation.

Wound dressings are widely used to protect wounds and promote healing. The water absorption and antifriction properties of dressings are important for regulating the moisture balance and reducing secondary damages during dressing changes. Herein, we developed a hyaluronic acid (HA)-based foam dressing prepared via the lyophilization of photocrosslinked HA hydrogels with high water absorption and antiadhesion properties. To fabricate the HA-based foam dressing (HA foam), the hydroxyl groups of the HA were modified with methacrylate groups, enabling rapid photocuring. The resulting photocured HA solution was freeze-dried to form a porous structure, enhancing its exudate absorption capacity. Compared with conventional biopolymer-based foam dressings, this HA foam exhibited superior water absorption and antifriction properties. To assess the wound-healing potential of HA foam, animal experiments involving SD rats were conducted. Full-thickness defects measuring 2 × 2 cm2 were created on the skin of 36 rats, divided into four groups with 9 individuals each. The groups were treated with gauze, HA foam, CollaDerm®, and CollaHeal® Plus, respectively. The rats were closely monitored for a period of 24 days. In vivo testing demonstrated that the HA foam facilitated wound healing without causing inflammatory reactions and minimized secondary damages during dressing changes. This research presents a promising biocompatible foam wound dressing based on modified HA, which offers enhanced wound-healing capabilities and improved patient comfort and addresses the challenges associated with conventional dressings.

Topical Treatment for Dry Eye Disease Related to Sjögren's Syndrome: A Systematic Review

Abstract
 Introduction & Objectives : Sjögren’s syndrome (SS) is a systemic autoimmune disorder characterized by dry eyes and dry mouth caused by inflammation in exocrine glands. Dry eye with SS is often more severe than non-SS dry eye and can greatly affect patients’ quality of life, thus treatment modalities must be selected carefully. This study aims to evaluate the recent studies on topical treatment for dry eye disease related to SS and provide evidence based recommendation for clinical practice.
 Methods : Electronic literature search was performed through the PubMed and Cochrane database from the last 10 years. We only included studies with prospective clinical trial design, a follow-up period of at least 4 weeks, and had outcome parameters among the following: Ocular Surface Disease Index, Schirmer test, tear break up time, tear meniscus height, and corneal fluorescein staining.
 Results : Fifteen studies were selected from 125 articles retrieved. We identified clinical trials using tacrolimus, cyclosporine, cortisol phosphate, diquafosol, rebamipide, fluorometholone, hydrocortisone, clobetasone butyrate, autologous serum, autologous platelet lysate, artificial tear, and various type of vehicles including hyaluronic acid, sodium hyaluronate, almond oil, ceftazidime,or saline solution.
 Conclusion : Cyclosporine has comparably equal efficacy to corticosteroid eye drops in improving signs and symptoms of dry eye in SS, but with a better safety for long-term use. Autologous serum is also an effective therapy with the best concentration being 100% serum (no dilution). Diquafosol is a promising therapy but more research is needed to confirm its efficacy and safety.

P525 Utilisation of endoscopic ultrasonography for submucosal cushion measurement to determine eligibility for endoscopic submucosal dissection in ulcerative colitis-associated dysplasia: A case series

Abstract Background Endoscopic submucosal dissection (ESD) has gained traction as an effective therapy for ulcerative colitis (UC)-associated dysplasia, yet identifying fitting ESD candidates is challenging by substantial submucosal (SM) fibrosis from chronic inflammation. We report our experience utilising endoscopic ultrasonography (EUS) to assess ESD eligibility by measuring SM cushion thickness. Methods Retrospective case-series includes nine patients who were diagnosed or referred to as UC-associated dysplasia in surveillance colonoscopies between August 2017 and October 2023. After scanning dysplastic lesions (Fig A-B), hyaluronic acid solution was injected into the SM layer (Fig C). EUS with a mini-probe quantified SM cushion beneath the dysplastic lesion (Fig D), and ESD was performed in cases with at least 2.0 mm of SM cushion thickness (Fig E-F). Results Among ten cases from nine patients, eight cases met the criteria and underwent ESD, while two cases (Patient 3, Patient 7) were regarded as unsuitable for ESD with SM cushion thickness less than 2.0 mm. Median disease duration was 19 years, and median age at diagnosis of UC-associated dysplasia was 50 years. Median SM cushion thickness ranged from 4.2 to 6.9 mm. Median procedure time was 50 minutes, and median size of resected specimens and lesions were 31.5 x 24.5 mm and 16.0 x 12.5 mm, respectively. en bloc resection was achieved in all cases, with an 87.5% R0 resection rate. No perforation occurred; only one required post-discharge endoscopic bleeding control after four days post-discharge. Conclusion EUS-measured SM cushion thickness may be a valid approach that provides an objective criterion for determining ESD eligibility in UC-associated dysplasia. This would help guide individualised treatment in UC-associated dysplasia, reducing unnecessary procedures or surgery.

Effect of carboxymethyl cellulose, icodextrin and hyaluronic acid solutions on postoperative intraabdominal adhesion formation in rabbits and the role of cytokines in intraabdominal adhesion formation

In this study, the aim was to investigate the effects of 1% CMC, 4% ICO and 0.4% HA solutions in preventing postoperative IAs and their contribution to peritoneal wound healing, as well as the relationship of cytokines with the formation of postoperative IAs in rabbits. The material of the study consisted of 32 healthy rabbits. Rabbits underwent median laparotomy following general anesthesia. Serosal abraded was created at the antimesenteric border of the cecum. Next, a 3 × 2 cm peritoneum was excised on the right abdominal wall and the defect was closed using with a 2/0 silk suture. The rabbits were randomly assigned to either of the following four treatment groups: CNT (0.9% NaCl), ICO (4% icodextrin), HA (0.4% hyaluronic acid) and CMC (1% carboxymethyl cellulose). Both cecum and peritoneal surfaces were treated with 20 ml each of treatment solutions. On the 7th postoperative day, the rabbits were euthanized with a lethal dose of sodium pentobarbital and the degree of adhesion was evaluated. Samples taken from the peritoneal defect were examined histopathologically and tissue hydroxyproline levels were measured. Serum TNF-α, IL-1 and IL-6 levels were measured from blood samples taken before the surgery and at 1, 6, 24 and 48 hours after the surgery. It was observed that the adhesion grade in the HA group (p < 0.05) and CMC group (p < 0.01) was significantly lower than the control group. Although peritoneal tissue hydroxyproline levels were lower in the other groups compared to the control group, they were not statistically significant (p > 0.05). In rabbits with adhesion formation, it was determined that TNF-α levels increased at the 6th postoperative hour (p < 0.05), and IL-6 levels increased at the 6th, 24th and 48th postoperative hours (p < 0.001) compared to preoperative. In this study, treating tissues with 0.4% HA and 1% CMC solutions suppressed peritoneal inflammation, and this resulted in an increase in the levels of proinflammatory cytokines TNF-α and IL-6. It has been determined that the application of these solutions reduces postoperative adhesion formation. It was concluded that TNF-α and especially IL-6, which are proinflammatory cytokines, can be a non-invasive biomarker in determining postoperative IA formation and evaluating the adhesive process.

Neuroprotective properties of Na+/H+-exchanger isoform-1 inhibitor in experimental POAG

Introduction: Worldwide glaucoma is the leading cause of irreversible vision loss. The processes associated with the loss of retinal ganglion cells are multifactorial and have much in common with neurodegenerative diseases. Therefore the search for means to prevent the death of retinal neurons is an important task of modern pharmacology. Materials and Methods: The study was conducted on male Wistar rats. Glaucoma was modeled by injecting a 1% solution of hyaluronic acid into the anterior chamber of the eye. The IOP level was recorded on the 0th, 63rd and 73rd days of the experiment. The effectiveness of the drugs was evaluated based on the results of ophthalmoscopy, electroretinography, followed by the determination of gene expression. Results and Discussion: In the group with RU-1355 correction, the fundus picture improved; the index in the group was 18.0% lower compared to the model. The introduction of the RU-1355 compound provided an increase in the a-wave amplitude by 18.1%, and b-wave amplitude by 39.0% relative to the group with pathology. The most pronounced effect was observed on the expression level of BDNF, Bcl-2, Caspase 3 and NF-κB p65, which indicates that the compound has the capacity to influence the slowdown of the apoptosis process through an increase in the neurotrophic factor and the anti-apoptotic factor Bcl-2. Conclusion: RU-1355 has neuroprotective properties, which was expressed by a decrease in ophthalmoscopic manifestations, preservation of the b-wave amplitude of the electroretinogram and the influence on gene expression of factors involved in apoptosis and neuroprotection. Based on the pharmacological activity of the RU-1355 compound in relation to POAG, further study of its action against other retinal diseases is promising.

The effect of hyaluronic acid concentration on the rheological and tribological properties of artificial synovial fluid base solutions

Synovial joints are a basic part of the human body. Lack of proper lubrication of joints can lead to significant wear of their surfaces. The tribological and rheological properties of artificial synovial fluid solutions based on hyaluronic acid were studied. It was found that the concentration of selected hyaluronic acid solutions significantly affects the investigated parameters. The most promising results were obtained for 8 wt% hyaluronic acid solution, which showed the highest viscosity and wettability, and the lowest wear.

Layer-by-layer assembly of poly-l-lysine/hyaluronic acid protein reservoirs on poly(glycerol sebacate) surfaces

The modification of biomaterial surfaces has become increasingly relevant in the context of ongoing advancements in tissue engineering applications and the development of tissue-mimicking polymer materials. In this study, we investigated the layer-by-layer (LbL) deposition of polyelectrolyte multilayer protein reservoirs consisting of poly-l-lysine (PLL) and hyaluronic acid (HA) on the hydrophobic surface of poly(glycerol sebacate) (PGS) elastomer. Using the methods of isothermal titration calorimetry and surface plasmon resonance, we systematically investigated the interactions between the polyelectrolytes and evaluated the deposition process in real time, providing insight into the phenomena associated with film assembly. PLL/HA LbL films deposited on PGS showed an exceptional ability to incorporate bone morphogenetic protein-2 (BMP-2) compared to other growth factors tested, thus highlighting the potential of PLL/HA LbL films for osteoregenerative applications. The concentration of HA solution used for film assembly did not affect the thickness and topography of the (PLL/HA)10 films, but had a notable impact on the hydrophilicity of the PGS surface and the BMP-2 release kinetics. The release kinetics were successfully described using the Weibull model and hyperbolic tangent function, underscoring the potential of these less frequently used models to compare the protein release from LbL protein reservoirs.

Slippery Viscosity-Sensing Platform with Time Readout for the Detection of Hyaluronidase and Its Inhibitor.

Hyaluronidase (HAase) is a biomarker for cancer, and its detection is of great significance for early diagnosis. However, the requirement of sophisticated instruments, tedious operation procedures, and labeled molecules of conventional HAase biosensing methods hampers their widespread applications. Herein, we report a portable slippery viscosity-sensing platform with time readout for the first time and demonstrate HAase and tannic acid (TA, HAase inhibitor) detection as a model system. HAase specifically cleaves hyaluronic acid (HA) and decreases HA solution viscosity, thereby shortening the aqueous droplet's sliding time on a slippery surface. Thus, the HA solution viscosity alteration due to enzymatic hydrolysis is used to quantify the HAase concentration through the difference in the sliding time of the aqueous droplets on a slippery surface. The developed HAase sensing platform exhibits high sensitivity with a minimum detection limit of 0.23 U/mL and excellent specificity without the use of specialized instruments and labeled molecules. HAase detection in actual urine samples by a standard addition method is performed as well. Moreover, the quantitative detection of TA with an IC50 value of 37.68 ± 1.38 μg/mL is achieved. As an equipment-free, label-free, and high-portability sensing platform, this method holds promise in developing a user-friendly and inexpensive point-of-care testing (POCT) device for HAase detection, and its use can be extended to analyze other analytes with different stimuli-responsive polymers for great universality and expansibility in biosensing applications.

Location of Polyelectrolytes in Swollen Lipid Oligobilayers.

Osteoarthritis is caused by degeneration of the cartilage, which covers the bone ends of the joints and is decorated with an oligolamellar phospholipid (PL) bilayer. The gap between the bone ends is filled with synovial fluid mainly containing hyaluronic acid (HA). HA and PLs are supposed to reduce friction and protect the cartilage from wear in joint movement. However, a detailed understanding of the molecular mechanisms of joint lubrication is still missing. Previously, we found that aqueous solutions of HA and poly(allylamine hydrochloride) (PAH), the latter serving as a polymeric analogue to HA, adsorb onto the headgroups of surface-bound 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) oligobilayers and significantly enhance their stability with respect to shear forces, typically occurring in joint movement. We now investigated the precise location of PAH chains across the lipid films in neutron reflectivity measurements, as bridging of the oligobilayers by polyelectrolytes (PEs) might be the cause for their improved mechanical stability. In a first set of experiments, we used hydrogenated PAH and chain-deuterated DMPC (DMPC-d54) to improve the contrast between the lipids and potentially intruding PAH. However, due to difficulties in distinguishing between incorporation of water and PAH, penetration into the lipid chain region could hardly be proven quantitatively. Therefore, we designed a more elaborate experiment based on mixed films of DMPC-d54 and hydrogenated DMPC, which is insensitive to water penetration into the films. Beside facilitating a detailed structural characterization of the oligolamellar system, this elaborate approach showed that PAH adsorbs to the DMPC heads and penetrates the lipid tail strata. No PAH was found in the lipid head strata, which excludes bridging of several lipid bilayers by the PE chains. The data are consistent with the assumption that PAH bridges are formed between the headgroups of two adjacent bilayers and contribute to the enhanced mechanical stability.

Gripping performance of soft grippers with fingerprint-like surface texture for objects with slippery surfaces

Soft robots face challenges when gripping and manipulating objects in lubricated environments, and one of the key issues in medical lubrication conditions in particular. In this study, soft actuators with independent pneumatic driven DIP and PIP joints are designed and prepared based on the anatomy of human fingers. The soft actuators are used to mimic the tip pinch action of the index finger and thumb, achieving dexterous grasping postures adapted to daily life, primarily for fine operation tasks. The bending capability, thrusting force, and fatigue life of the soft actuators are tested. Furthermore, by mimicking the three common fingerprint patterns (i.e., whorls, loops, and arches), three macroscopic surface textures were designed and prepared on the surface of silicone rubber materials. Tribological properties of the surface textures are studied under medical lubrication conditions with hyaluronic acid solution as lubricant. Based on this, tip pinch gripping experiments are conducted on standard shape objects, common medical devices, and biological materials with surface mucus layer. The results showed that the surface of the soft actuators can fit well with the surface of the gripped objects, thereby achieving a larger contact area and enabling the gripping of standard items and common medical devices. Moreover, for biological materials with mucous layer of significant differences in physiological function, the weight that can be gripped is significantly higher than that of the gripper without surface texture.

Polysaccharide-Based Composite Hydrogel with Hierarchical Microstructure for Enhanced Vascularization and Skull Regeneration.

Critical-size skull defects caused by trauma, infection, and tumor resection raise great demands for efficient bone substitutes. Herein, a hybrid cross-linked hierarchical microporous hydrogel scaffold (PHCLS) was successfully assembled by a multistep procedure, which involved (i) the preparation of poly(lactic-co-glycolic)/nanohydroxyapatite (PLGA-HAP) porous microspheres, (ii) embedding the spheres in a solution of dopamine-modified hyaluronic acid and collagen I (Col I) and cross-linking via dopamine polyphenols binding to (i) Col I amino groups (via Michael addition) and (ii) PLGA-HAP (via calcium ion chelation). The introduction of PLGA-HAP not only improved the diversity of pore size and pore communication inside the matrix but also greatly enhanced the compressive strength (5.24-fold, 77.5 kPa) and degradation properties to construct a more stable mechanical structure. In particular, the PHCLS (200 mg, nHAP) promoted the proliferation, infiltration, and angiogenic differentiation of bone marrow mesenchymal stem cells in vitro, as well as significant ectopic angiogenesis and mineralization with a storage modulus enhancement of 2.5-fold after 30 days. Meanwhile, the appropriate matrix microenvironment initiated angiogenesis and early osteogenesis by accelerating endogenous stem cell recruitment in situ. Together, the PHCLS allowed substantial skull reconstruction in the rabbit cranial defect model, achieving 85.2% breaking load strength and 84.5% bone volume fractions in comparison to the natural cranium, 12 weeks after implantation. Overall, this study reveals that the hierarchical microporous hydrogel scaffold provides a promising strategy for skull defect treatment.

Hydrogel Contact Lenses Embedded with Amine-Functionalized Large-Pore Mesoporous Silica Nanoparticles with Extended Hyaluronic Acid Release.

Contact lenses (CLs) have emerged as an effective method for delivering ophthalmic drugs. In this research, we designed hydrogel CLs capable of extended release, utilizing large-pore mesoporous silica nanoparticles (LPMSNs) to deliver hyaluronic acid (HA) for treating dry eye syndrome. LPMSNs were functionalized with amine groups (LPMSN-amine) to enhance HA loading and release capacity. In vitro release studies demonstrated that LPMSN-amine CLs exhibited superior slower HA release than LPMSN-siloxane and standard CLs. Within 120 h, the cumulative amount of HA released from LPMSN-amine CLs reached approximately 275.58 µg, marking a 12.6-fold improvement compared to standard CLs, when loaded from 0.1 wt% HA solutions. Furthermore, LPMSN-amine CLs effectively maintained moisture, mitigating ocular surface dehydration, making them a promising solution for dry eye management. This study successfully developed LPMSN-amine CLs for extended HA release, identifying the optimal functional groups and loading conditions to achieve sustained release.

Can We Do Anything Else before Removing a Button Battery from the Esophagus?-Hyaluronic Acid.

This article tests the protective effect of a commercially available mixture of hyaluronic acid, chondroitin sulfate, and poloxamer 407 on the damage caused by the exposure of esophageal mucosa to button batteries in an animal model. Experimental study. Sixty porcine esophageal samples were distributed in three groups: control (CG), exposure (EG), and exposure-protection (EPG). In EG and EPG, one CR2032 button battery per sample was inserted, both were subdivided into 2-, 4-, 6-, and 24-hour exposure subgroups, with subsequent battery removal. EPG samples were irrigated with the solution 1 hour after battery exposure. Esophageal pH and final voltage of the battery were measured. pH in CG remained stable. No significant differences in pH at 1 hour were found between EG and EPG. In EPG, the pH of the mucosa exposed to the anode was lower than in GE at 2 hours (12.44 vs. 11.89, p = 0.203) and 4 hours (13.78 vs. 11.77, p < 0.0001). In the cathode pH was significantly higher in EG at 2 hours (2.5 vs. 4.11, p < 0.0001), 4 hours (2.33 vs. 4.78, p < 0.0001), and 6 hours (2.17 vs. 2.91, p < 0.0001). Significant voltage reduction at 1 hour was found in EG compared to EPG (0.48 vs. 1.08 V, p = 0.004). Exposure to hyaluronic acid solution buffers the acidification on the side exposed to the cathode and basification on the anode. This effect can be maintained up to 3 to 5 hours, even after stopping its application. Our results suggest that a solution containing hyaluronic acid could be used as an esophageal protector after accidental ingestion of button batteries.

Barrier Graphene Oxide on a CoCr Alloy via Silane/GO Covalent Bonding and Its Electrochemical Behavior in a Simulated Synovial Fluid Electrolyte

In this work, impermeable and ultrathin surface nanomodifications for joint applications based on graphene oxide (GO) are assembled on CoCr surfaces via covalent immobilization between GO nanosheets and silane monolayers. Two silane curing temperatures, 45 °C for 24 h and 75 °C for 30 min, on CoCr surfaces and two incubation times for GO suspension, 12 h and 24 h, on silanized CoCr surfaces are prepared. Electrochemical characterization is performed using electrochemical impedance spectroscopy (EIS) in a 3 g/L hyaluronic acid solution. Results show that GO nanosheets immobilized with silane covalent bonding confer impermeability of sp2 networks on GO and strong interfacial adhesion of GO sheets anchored to silanized CoCr via organosilane chemistry, which prevents the permeation of oxidant species at the metal interface. At short GO incubation times (12 h), the Rs values decrease with the immersion time, indicating that small species, such as metal ions, are able to diffuse through the interlayer gaps of nanolayers. Longer GO incubation times (24 h) favor the formation of bonds between the GO and the silane, thus slowing downdiffusion and metal ion release into the medium. EIS data confirm the impermeability of GO nanocoatings with lengthening GO incubation time for medical application of metallic implants.

Histopathologic analysis of hyaluronic acid composite solution following intravascular injection: Variability and safety.

Although a composite solution of non-crosslinked hyaluronic acid is generally considered safe, few studies have investigated its safety after intravascular injection. Male Sprague-Dawley rats were administered 0.05 mL of a non-crosslinked hyaluronic acid composite solution via intravascular injection into bilateral inferior epigastric arteries (IEA). Artery samples were obtained at multiple time points for histopathologic analysis. Bilateral abdominal flaps supplied by the IEA were lifted and the same dose of solution was injected into the artery, and flap survival was analyzed. Histopathologic analysis showed that the non-crosslinked hyaluronic acid composite solution remained temporarily in the artery lumen following intravascular injection. With continuous blood flow, the filler gradually disintegrated and the artery became recanalized. At 24 h, no filler remained in the lumen. At 7 days after the filler was injected into the IEA feeding the flap, there was no significant difference between the experimental and control groups with respect to flap survival rate. Non-crosslinked hyaluronic acid composite solution is relatively safe when a minimal volume is administered by intravascular injection. The filler will remain in the vessel for a short time, after which the vessel recanalizes.

Evaluation of Non-Cross Linked Xeno-Free Hyaluronic Acid Solutions as Visco Elastic Biomaterials.

Hyaluronic acid (HA) is a naturally occurring biodegradable, high molecular weight, non-sulfated glycosaminoglycan (GAG) polymer known for its excellent biocompatibility. HA-based products are widely used as viscosupplements, dermal fillers, and ophthalmic lubricants in clinical settings. Although animal and bacterial-derived HA are commonly reported, plant-sourced HA is not frequently reported. In this study, we have evaluated various viscoelastic properties of one such plant-based HA solution and propose them as an alternative to existing animal/bacteria-sourced HA. The viscoelastic properties of plant-sourced HA solution of various concentrations (0.1%, 0.5%, 1%, and 2% in PBS) were studied using a rheometer at 37°C. Flow curves, amplitude sweep studies, and frequency sweep studies were performed and compared for all HA solutions. The HA solutions displayed shear-thinning behavior, which is an important characteristic of an injectable biomaterial. The 0.1 and 0.5% HA were found to have viscoelastic properties appropriate for eye lubricants, while 1 and 2% HA solutions showed properties suitable for soft tissue fillers. Frequency sweep studies indicated that all the samples are typically viscoelastic liquids with a loss modulus (G″) higher than the storage modulus (G'). This indicated that the samples needed further processing like crosslinking of HA or using higher molecular weight HA to be suitable as viscosupplements. However, the frequency sweep studies also indicated that these solutions can be used as soft tissue fillers of any type based on the G' and tan δ values. The plant-sourced HA solutions are found to exhibit good shear-thinning properties with viscoelastic properties suitable for eye lubricants and soft tissue fillers. However, to be used as viscosupplements, the viscoelastic properties of HA solutions have to be further modified through non-toxic crosslinking strategies, and hydrophobic derivatives as well as by using high molecular weight HAs.

Long-Term Activity and Safety of a Low-Dose Hydrocortisone Tear Substitute in Patients with Dry Eye Disease

Purpose A clinical trial was conducted to evaluate the activity of a new artificial tear containing hyaluronic acid (HA) and low-dose hydrocortisone to control dry-eye disease (DED) symptoms. Methods a randomized, controlled, double-masked study was carried out at the Ocular Surface and Dry Eye Center, “Luigi Sacco” University Hospital (Milan, Italy), between June 2020 and June 2021. The study involved patients with DED for at least 6 months. After an initial 7-day treatment with corticosteroid, the treatment with the new artificial tear (four-times a day for 6 months) was compared with a control HA solution. Results A total of 40 patients were considered. We observed a significant improvement in the frequency and intensity of DED symptoms in both groups. After corticosteroid discontinuation, the maintenance of the therapeutic advantage was observed only in the treatment group, which also showed a significant improvement of the tear film break-up time (p ≤ 0.05) and infiltrated macrophages (p < 0.05). A significant reduction in fluorescein and Lissamine staining (p < 0.05) was observed in the treatment group, suggesting damage reduction at both corneal and conjunctival levels. Intraocular pressure did not change at the end of the treatment period and was maintained within the normal range, sustaining the product’s safety. Conclusions Our findings support the prolonged use of the new eye drop with low-dose hydrocortisone, also in the DED initial stages, to prevent the degenerating towards a chronic condition (http://www.isrctn.com/ISRCTN16288419).

A facile bioorthogonal chemistry-based reversible to irreversible strategy to surmount the dilemma between injectability and stability of hyaluronic acid hydrogels

Injectable and stable hydrogels have great promise for clinical applications. Fine-tuning the injectability and the stability of the hydrogels at different stages has been challenging due to the limited number of coupling reactions. A distinct “reversible to irreversible” concept using a thiazolidine-based bioorthogonal reaction between 1,2-aminothiols and aldehydes in physiological conditions to surmount the dilemma between injectability and stability is presented for the first time. Upon mixing aqueous solutions of aldehyde-functionalized hyaluronic acid (SA-HA) and cysteine-capped ethylenediamine (DI-Cys), SA-HA/DI-Cys hydrogels formed through reversible hemithioacetal crosslinking within 2 min. The reversible kinetic intermediate facilitated thiol-triggered gel-to-sol transition, shear-thinning and injectability of the SA-HA/DI-Cys hydrogel but then converted to the irreversible thermodynamic network after injection, thereby permitting the resulting gel with improved stability. As compared to the Schiff base hydrogels, the hydrogels generated from this simple, yet effective concept awarded improved protection to the embedded mesenchymal stem cells and fibroblast during injection, retained the cells homogeneously within the gel, and allowed them further proliferation in vitro and in vivo. There is potential for the proposed approach of “reversible to irreversible” based on thiazolidine chemistry to be applied as a general coupling technique for developing injectable and stable hydrogels for biomedical applications.