Hyaluronic Acid Solution Research Articles

Relationship between hydration layer thickness and friction property of contact lens with the addition of eye drop ingredients

Contact Lens (CL) causes eye damage and discomfort by increasing friction with upper eyelids. To improve the safety and wearing comfort of CL, eye drop has an important role in reducing friction on CL. Therefore, it is essential to understand the friction mechanism between a CL and an upper eyelid in eye drop. In a previous study, we investigated the relationship between the hydration layer thickness and frictional properties of CL surfaces in a saline solution. We used a high-resolution tribometer and frequency-modulation atomic force microscopy (FM-AFM) to observe the hydration layer. The hydration layer of the CL in a saline solution was found to increase or decrease in thickness because of micro abrasion However, the effects of eye drops on friction mechanism of CL have not yet been investigated. In this study, we investigated the effects of hyaluronic acid on CL surface friction and hydration layer thickness. In friction tests, the coefficient of friction of hyaluronic acid solution was higher than that of saline solution, regardless of the amount of hyaluronic acid added. In addition, FM-AFM observations indicated that the hydration layer thickness on the CL surface increased in PBS with hyaluronic acid solution compared to that in saline solution. Therefore, the frictional properties of the CL in PBS with hyaluronic acid solution were not determined by the hydration layer thickness.

Intra-socket application of Hyaluronic acid reduces pain and swelling following wisdom teeth removal

Background:Hyaluronic acid (HA) has the potential to promote wound healing. Pain and swelling with trismus are common sequalae post wisdom teeth removal. This study aims to investigate the effectiveness of intra-socket HA solution to reduce these uncomfortable post-operative events.Materials and methods:30 patients underwent bilateral extractions of mandibular wisdom teeth for this study. Intra-socket application of 0.7 ml 20 mg/2 ml HA solution (Hyalgun) with Gel foam as a scaffold in study site versus Gel foam only on control site was conducted via a split mouth study design. Data collection of five facial reference points for swelling and maximum mouth opening was recorded during the pre-operative period and post-operative 2nd and 7th day. The VAS pain score at post-op 1st, 2nd and 3rd day and the number of analgesics for the 7-day post-operative duration were evaluated.Results:The HA group demonstrated statistically significant less swelling, trismus and analgesia consumption on the 2 and 7 days after surgery. VAS scores on day 1, 2 and 3 after surgery (P = 0.05) were significantly less in the HA group compared to the control group.Conclusion:The application of intra-socket HA has a positive effect for reducing postoperative pain and swelling with trismus after the lower third molar intervention (LTMI).

Investigating protein diffusivities in diluted hyaluronic acid solutions using dynamic light scattering.

This study aimed to investigate the diffusivities of lysozyme (LYS), ovalbumin (OVA), and hyaluronic acid (HA) in buffered solvents using dynamic light scattering (DLS). For protein/solvent and HA/solvent binary systems, the diffusion coefficients of protein or HA were obtained from autocorrelation function (ACF) curve fitting. Whereas, for protein/HA/solvent ternary systems, the two eigenvalues of the mutual diffusion coefficient matrix were obtained from ACF curve fitting. The results of binary systems showed that at low ionic strength, the diffusion coefficients of protein and HA increased linearly with concentration; at high ionic strength, the diffusion coefficients of OVA and LYS were independent on protein concentration; for HA, the positive linear relationship between diffusion coefficient and concentration existed at high and low ionic strengths, but the slope at high ionic strength was smaller compared to that at low ionic strength. For OVA/HA/solvent ternary systems, the sum of two eigenvalues (D1DLS + D2DLS) was slightly smaller compared to (DOVA + DHA), where DOVA and DHA were the diffusion coefficients in their binary systems. On the contrary, for LYS/HA/solvent ternary systems, (D1DLS + D2DLS) were significantly smaller than (DLYS + DHA) and the diffusion coefficients in binary and ternary systems exhibited an opposite trend with respect to ionic strength change. The DLS and MD simulation results indicated strong attractive intermolecular interaction existed between LYS and HA molecules, especially at low ionic strength. By using DLS, it was possible to characterize the diffusion coefficients of diluted protein/HA binary and ternary systems.

Enlargement of Phimotic Capsulorhexis Using Plasma Energy: A Case Series

Purpose: to evaluate the effectiveness and safety of the plasma ablation technique of Fugo blade system to enlarge phimotic capsulotomies in the management of anterior capsule contraction syndrome.Patients and methods. Results of the enlargement of phimotic capsulotomies using the plasma ablation technique in 17 patients with anterior capsule contraction syndrome (10 men and 7 women, 18 eyes; average age — 73.8 ± 9.6 years) were retrospectively analyzed. Surgically, after pupil dilation, the anterior chamber was irrigated with a viscoelastic device (1.4 % solution of hyaluronic acid), and the tip of the Fugo blade was inserted through a 2.0–2.2 mm wide corneal incision. After slightly touching the anterior capsule, the apparatus was activated, and its tip was moved in a concentric manner, excising the required size of the fibrosed anterior capsule in a resistance-free fashion. Finally, the viscoelastic material was aspirated, and the incisions were hydrated.Results. Phimotic capsulotomies were enlarged in all cases. Except for three cases where the bimanual technique was required to ablate the anterior capsule, all other cases were managed single-handedly. The use of cohesive viscoelastic device (1.4 % solution of hyaluronic acid) made it possible to perform this procedure with minimum trauma and under visual control. No serious complications were encountered during surgery or in the early postoperative period. Patients were discharged 1–2 days after surgery. Corneal edema, which was observed in six eyes, resolved within 3–4 days. Visual acuity improved in all cases, except for 2 patients with complete glaucomatous optic atrophy. IOP remained under control in all cases. No negative effect on the hypotensive results of previous glaucoma surgeries was observed.Conclusion. The plasma-generating Fugo blade system is an effective and safe tool to enlarge phimotic capsulorhexis in a resistance-free fashion. It is easy to use, mastering of new surgical skills is not required, surgical trauma is minimal, the surgical time is reduced, and the patient’s rehabilitation period is significantly shortened.

Intraarticular injections of platelet rich plasma and plasma rich in growth factors with arthrocenthesis or arthroscopy in the treatment of temporomandibular joint disorders: A systematic review

Intra-articular platelet rich plasma injections [PRP] or platelet rich growth factors [PRGF] injections have been used as therapeutic treatment options for patients with temporomandibular joint disorder [TMD] in recent years. The purpose of this paper is to evaluate the level of the available scientific evidence in the current literature on the benefits of applying PRP or PRGF injections to patients with TMD simultaneously or after arthrocentesis or arthroscopy to reduce post-operative pain and improve temporomandibular joint function. This systematic review was conducted according to PRISMA criteria and an electronic database search was carried out in the PubMed, Scopus and Cochrane databases during May 2021. The patients in the study group were injected with intra-articular PRP or PRGF simultaneously or after arthrocentesis or arthroscopy while the patients in the control group had arthrocentesis or arthroscopy without an intra-articular injection or received an injection of hyaluronic acid or Ringer's lactate solution. Eight randomised controlled clinical trials were selected. The PRP and PRGF intra-articular injections demonstrated significant differences in terms of pain reduction in three studies and improved mandibular function in two. The treatment with PRP or PRGF intra-articular injections demonstrated slightly better clinical results but of little significance in comparison with the control group. Evidence of their effectiveness is crucial to establish them as non-invasive treatments and as an affordable option for treating some types of TMDs. In accordance with Evidence-based dentistry principles, this review has been assigned a C recommendation.

Hyaluronic Acid In Vitro Response: Viability and Proliferation Profile of Human Chondrocytes in 3D-Based Culture

This study aimed to evaluate the efficacy of hyaluronic acid in the viability and proliferation profile of human femoral-tibial joint cartilage affected by osteoarthritis using in vitro models of chondrocytes in a 2-dimensional (2D)- and 3-dimensional (3D)-based culture model by spheroids. In vitro study of knee cartilage affected by osteoarthritis that required surgical treatment. Samples were cultured and exposed to hyaluronic acid (100 and 500 μM; intervention group) or vehicle solution. In monolayer or 2D culture, proliferation and cell viability were measured, and nuclear morphometry was analyzed by 4',6'-diamino-2-fenil-indol (DAPI) staining. The 3D-based culture established from the culture of articular cartilage of patients submitted to total knee arthroplasty evaluated the diameter, viability, and fusion ability of the chondrospheres created. Samples from 3 patients resulted in viable cultures, with chondrocyte cells exhibiting a potential for cell proliferation and viability to establish a culture. Hyaluronic acid (100 and 500 μM) improved chondrocyte viability and proliferation up to 72 hours in contact when compared with the control group, and no nuclear irregularities in morphology cell characteristics were observed by DAPI. In the 3D evaluation, hyaluronic acid (500 μM) improved the cellular feedback mechanisms, increasing the survival and maintenance of the chondrospheres after 7 days of analysis, showing the intrinsic capacity of chondrospheres grouped in the attempt to rearrange and reestablish new articular tissue. The 2D- and 3D-based culture models with hyaluronic acid improved chondrocyte viability and proliferation and demonstrated the ability of freshly formed chondrospheres to undergo fusion when placed together in the presence of hyaluronic acid.

Adsorption/desorption behavior of hyaluronic acid fragments at charged hydrophobic surface

This work reveals the growing potential of novel electrochemical methods that are applicable for polysaccharides. It was shown for the first time that the molecules of hyaluronic acid (HA) exhibit electrochemical response using phase-sensitive alternating current (AC) voltammetry in phase-out mode. Adsorption and desorption processes of HA fragments at a charged interface of mercury electrode were observed in buffered HA solutions. Electrostatic and hydrophobic manners of interactions were distinguished for native hyaluronan fragments in a wide electric potential range. The AC voltammetry response depended on the temperature, concentration, and length of HA chains. Results of this work open possibilities for further structural characterization of widely used HA fragments and understanding manners of interactions with charged hydrophobic surfaces that could be useful in the future for understanding HA interactions at biological levels.

Strategy for osteoarthritis therapy: Improved the delivery of triptolide using liposome-loaded dissolving microneedle arrays

Osteoarthritis (OA) is a chronic disease that seriously impairs people’s physical function and quality of life. Triptolide (TP), as a promising anti-inflammatory drug for the treatment of OA, has limited clinical application due to its severe systemic toxicity, poor solubility and rapid elimination in the body. To extend its application prospect for OA treatment. We have developed a liposome-loaded dissolving microneedle (DMN) system, which can effectively deliver poorly water-soluble TP and improve OA symptoms. To incorporate TP into DMNs, triptolide liposome (TP-Lipo) with entrapment efficiency of 90.25% was prepared by ethanol injection. Subsequently, TP-Lipo was concentrated by ultrafiltration tube and mixed with hyaluronic acid solution to prepare DMNs, TP-Lipo-loaded DMNs (TP-Lipo@DMNs) showed sufficient mechanical and insertion properties to penetrate about 200 μm of rat skin. The drug distribution in vivo showed that TP-Lipo@DMNs had a slow-release effect compared with intra-articular injection. In vivo pharmacodynamic research showed that TP-Lipo@DMNs significantly reduced knee joint swelling and the level of inflammatory cytokines (TNF-α, IL-1β, IL-6). Micro-CT and histological evaluation showed that TP-Lipo@DMNs effectively reduced cartilage destruction and alleviated OA symptoms. These results support that TP@Lipo@DMNs may be a promising option for OA treatment.

Hyaluronic Acid/Trehalose Ophthalmic Solution in Reducing Post-Cataract Surgery Dry Eye Signs and Symptoms: A Prospective, Interventional, Randomized, Open-Label Study.

The purpose of this prospective study was to evaluate the efficacy of the perioperative use of a hyaluronic acid (HA) and trehalose ophthalmic solution (Thealoz® Duo) in reducing post-cataract surgery dry eye signs and symptoms in patients with mild/moderate dry eye disease (DED). One hundred and twenty patients, scheduled for unilateral cataract surgery, were randomized into three groups: (1) group A: HA/trehalose three times/day in the preoperative week and for 5 postoperative weeks; (2) group B: HA/trehalose for only 5 postoperative weeks; (3) group C: no artificial tears. In groups A and B, OSDI (Ocular Surface Disease Index) questionnaire scores were significantly lower than group C at all the postoperative visits; in group A they were significantly lower than group B on the day of surgery, with similar results in the first and fifth weeks after surgery. In groups A and B, break-up time (BUT) was significantly higher than group C during the postoperative period (p ≤ 0.001). In comparison to the preoperative values, BUT in group A remained stable 7 days after surgery; however, in groups B and C, it significantly decreased. In conclusion, the HA/trehalose ophthalmic solution effectively reduced post-cataract surgery DED signs and symptoms in patients with mild/moderate DED, particularly if also administered in the preoperative period.

Multiscale Microrheology Using Fluctuating Filaments as Stealth Probes.

The mechanical properties of soft materials can be probed on small length scales by microrheology. A common approach tracks fluctuations of micrometer-sized beads embedded in the medium to be characterized. This approach yields results that depend on probe size when the medium has structure on comparable length scales. Here, we introduce filament-based microrheology using high-aspect-ratio semiflexible filaments as probes. Such quasi-1D probes are much less invasive than beads due to their small cross sections. Moreover, by imaging transverse bending modes, we simultaneously determine the micromechanical response of the medium on multiple length scales corresponding to the mode wavelengths. We use semiflexible single-walled carbon nanotubes as probes that can be accurately and rapidly imaged based on their stable near-IR fluorescence. We find that the viscoelastic properties of sucrose, polyethylene oxide, and hyaluronic acid solutions measured in this way are in good agreement with those measured by conventional micro- and macrorheology.

Hyaluronic Acid-Binding, Anionic, Nanoparticles Inhibit ECM Degradation and Restore Compressive Stiffness in Aggrecan-Depleted Articular Cartilage Explants.

Joint trauma results in the production of inflammatory cytokines that stimulate the secretion of catabolic enzymes, which degrade articular cartilage. Molecular fragments of the degraded articular cartilage further stimulate inflammatory cytokine production, with this process eventually resulting in post-traumatic osteoarthritis (PTOA). The loss of matrix component aggrecan occurs early in the progression of PTOA and results in the loss of compressive stiffness in articular cartilage. Aggrecan is highly sulfated, associates with hyaluronic acid (HA), and supports the compressive stiffness in cartilage. Presented here, we conjugated the HA-binding peptide GAHWQFNALTVRGSG (GAH) to anionic nanoparticles (hNPs). Nanoparticles conjugated with roughly 19 GAH peptides, termed 19 GAH-hNP, bound to HA in solution and increased the dynamic viscosity by 94.1% compared to an HA solution treated with unconjugated hNPs. Moreover, treating aggrecan-depleted (AD) cartilage explants with 0.10 mg of 19 GAH-hNP restored the cartilage compressive stiffness to healthy levels six days after a single nanoparticle treatment. Treatment of AD cartilage with 0.10 mg of 19 GAH-hNP inhibited the degradation of articular cartilage. Treated AD cartilage had 409% more collagen type II and 598% more GAG content than untreated-AD explants. The 19 GAH-hNP therapeutic slowed ECM degradation in AD cartilage explants, restored the compressive stiffness of damaged cartilage, and showed promise as a localized treatment for PTOA.

Efficacy of sodium hyaluronate in relieving nasal symptoms of children with intermittent allergic rhinitis: a randomized controlled trial.

Nasal irrigation is recommended as add-on therapy in patients with intermittent allergic rhinitis (AR). We aimed to evaluate the clinical efficacy of adding hyaluronic acid (HA) or normal saline solution (NSS) to nasal corticosteroid (NC) therapy as add-on therapy in improving quality of life and reducing nasal symptom scores of children with intermittent AR compared to NC therapy. In this 28-day long, open-label, randomized controlled trial, one puff of NC was administered once a day through both nostrils of 76 children with SAR (6-12years old), whose Total Nasal Symptom Score (TNSS) was ≥ 4. Twenty-six patients received NC only (Group 1); 24 patients received NSS (Group 2), and 26 patients received HA (Group 3) twice a day by means of nasal douche device. Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and TNSS were measured as subjective parameters, and nasal eosinophil count (NEC) in nasal cytology, nasal airflow (NAF), and resistance were measured as objective parameters. No significant difference was found in post-treatment between groups in terms of TNSS, PRQLQ, and NEC values. Mean values of post-treatment left NAF of the groups were significantly different (p = 0.030), and the mean value of Group 3 was the highest (mean ± SD = 247.62 ± 155.8 ccm/sn). In comparing pre- and post-treatment intragroup mean total NAR (TNAR) values, a statistically significant decrease was recorded only in group three (p = 0.025). The addition of HA to NC as an adjunct therapy in children with intermittent AR has limited beneficial effects in our study and deserves further investigation. The clinical trial registration number ID:NCT04752956.

The Influence of Technological Parameters on Morphology of Electrospun Nanofibers Based on Hyaluronic Acid

Electrospinning as a high-functioning, multi-operated, and advanced method of nanofiber production allowing to obtain fibrous materials based on different polymers for a wide range of biomedical and bioengineering applications. Hyaluronic acid is one of the most promising polymers for nanofiber formation due to its unique biological and biochemical properties. In spite of the difficulties and special features of the electrospinning from hyaluronic acid solutions, the amount of studies in this field is ever-growing. Unfortunately, there is a significant shortage of fundamental data describing the relations between the technological parameters and the nanofiber morphology. This study considers the key technological parameters of the electrospinning process such as applied voltage and flow volume rate and evaluates their influence on the morphology, mean diameter, and diameter distribution width of nanofibers based on native hyaluronic acid. The optimal range of the defined parameters has been established, at which the stability of the fiber formation is ensured. It is shown that by varying of the applied voltage and the flow volume rate of the polymer spinning solution, it is possible to control the properties of nanofibers.

Polyplexes of retinoic acid: an in vitro study of complex nanostructures against colorectal cancer cell line (HCT-15)

Despite recent advances in the treatment of human colon cancer, the chemotherapeutic efficacy against colon cancer is still unsatisfactory. The complexity in colorectal cancer treatment leads to new research in combination therapy to overcome multidrug resistance in cancer and increase apoptosis. The objective of the present research work was to develop polyplexes for co-delivery of plasmid DNA with retinoic acid against colorectal cancer cell line (HCT-15). Plain polyplexes were prepared using chitosan and hyaluronic acid solution (0.1% w/v), whereas retinoic acid polyplexes were prepared using ethanol: water (1:9 v/v) system. The particle size was observed in the order of chitosan solution > blank polyplex > retinoic acid-loaded polyplex. Encapsulation efficiency of retinoic acid was found to be 81.51 ± 4.33% for retinoic acid-loaded polyplex formulation. The drug release was observed to be in a controlled pattern with 72.23 ± 1.32% release of retenoic acid from polyplex formulation. Cell line studies of the formulation displayed better cell inhibition and low cytotoxicity for the retinoic acid-loaded polyplexes in comparison to pure retinoic acid, thus demonstrating better potential action against colorectal cancer cell line HCT-15. Retinoic acid-loaded polyplexes indicated higher potential for the delivery of the active whereas the cell line studies displayed the efficacy of the formulation against colorectal cancer cell line HCT-15.

Hyaluronic acid synthesis, degradation, and crosslinking in equine osteoarthritis: TNF-\u03b1-TSG-6-mediated HC-HA formation

BackgroundTNF-α-stimulated gene 6 (TSG-6) protein, a TNF-α-responsive hyaladherin, possesses enzymatic activity that can catalyze covalent crosslinks of the polysaccharide hyaluronic acid (HA) to another protein to form heavy chain-hyaluronic acid (HC-HA) complexes in pathological conditions such as osteoarthritis (OA). Here, we examined HA synthase and inflammatory gene expression; synovial fluid HA, TNF-α, and viscosity; and TSG-6-mediated HC-HA complex formation in an equine OA model. The objectives of this study were to (1) evaluate the TNF-α-TSG-6-HC-HA signaling pathway across multiple joint tissues, including synovial membrane, cartilage, and synovial fluid, and (2) determine the impact of OA on synovial fluid composition and biophysical properties.MethodsHA and inflammatory cytokine concentrations (TNF-α, IL-1β, CCL2, 3, 5, and 11) were analyzed in synovial fluid from 63 OA and 25 control joints, and HA synthase (HAS1-3), TSG-6, and hyaluronan-degrading enzyme (HYAL2, HEXA) gene expression was measured in synovial membrane and cartilage. HA molecular weight (MW) distributions were determined using agarose gel electrophoresis and solid-state nanopore measurements, and HC-HA complex formation was detected via immunoblotting and immunofluorescence. SEC-MALS was used to evaluate TSG-6-mediated HA crosslinking, and synovial fluid and HA solution viscosities were analyzed using multiple particle-tracking microrheology and microfluidic measurements, respectively.ResultsTNF-α concentrations were greater in OA synovial fluid, and TSG6 expression was upregulated in OA synovial membrane and cartilage. TSG-6-mediated HC-HA complex formation was greater in OA synovial fluid and tissues than controls, and HC-HA was localized to both synovial membrane and superficial zone chondrocytes in OA joints. SEC-MALS demonstrated macromolecular aggregation of low MW HA in the presence of TSG-6 and inter-α-inhibitor with concurrent increases in viscosity.ConclusionsSynovial fluid TNF-α concentrations, synovial membrane and cartilage TSG6 gene expression, and HC-HA complex formation were increased in equine OA. Despite the ability of TSG-6 to induce macromolecular aggregation of low MW HA with resultant increases in the viscosity of low MW HA solutions in vitro, HA concentration was the primary determinant of synovial fluid viscosity rather than HA MW or HC-HA crosslinking. The TNF-α-TSG-6-HC-HA pathway may represent a potential therapeutic target in OA.

Ortho Isomeric Mn(III) N-Alkyl- and Alkoxyalkylpyridylporphyrins-Enhancers of Hyaluronan Degradation Induced by Ascorbate and Cupric Ions.

High levels of hyaluronic acid (HA) in tumors correlate with poor outcomes with several types of cancers due to HA-driven support of adhesion, migration and proliferation of cells. In this study we explored how to enhance the degradation of HA into low-molecular fragments, which cannot prevent the immune system to fight tumor proliferation and metastases. The physiological solution of HA was exposed to oxidative degradation by ascorbate and cupric ions in the presence of either one of three ortho isomeric Mn(III) substituted N-alkyl- and alkoxyalkylpyridylporphyrins or para isomeric Mn(III) N-methylpyridyl analog, commonly known as mimics of superoxide dismutase. The changes in hyaluronan degradation kinetics by four Mn(III) porphyrins were monitored by measuring the alteration in the dynamic viscosity of the HA solution. The ortho compounds MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001) and MnTnHex-2-PyP5+ are able to redox cycle with ascorbate whereby producing H2O2 which is subsequently coupled with Cu(I) to produce the •OH radical essential for HA degradation. Conversely, with the para analog, MnTM-4-PyP5+, no catalysis of HA degradation was demonstrated, due to its inertness towards redox cycling with ascorbate. The impact of different Mn(III)-porphyrins on the HA decay was further clarified by electron paramagnetic resonance spectrometry. The ability to catalyze the degradation of HA in a biological milieu, in the presence of cupric ions and ascorbate under the conditions of high tumor oxidative stress provides further insight into the anticancer potential of redox-active ortho isomeric Mn(III) porphyrins.

Non-pharmacological remedies for post-viral acute cough.

The post-viral acute cough (PAC) is a widespread symptom, mainly in childhood and adolescence, and is usually associated with an acute upper respiratory infection, namely the common cold. The use of cough relievers is, therefore, impressive, as documented by the market data. There are many medical devices and dietary supplements for treating PAC, which contain non-pharmacological components. Ancient people used traditional herbs to treat PAC. Thus, a well-established tradition considers natural remedies as an effective and safe way to relieve PAC. The herbal agents include polyphenols, flavonoids, saponins, glucosides, and alkaloids. Also, the European Medicine Agency has recognized the value of plant extracts and other natural substances to treat PAC. Nevertheless, a few studies investigated the role of non-pharmacologic remedies for PAC. There is some evidence for honey, glycerol, Althea officinalis, Drosera rotundifolia, Grindelia, Hedera helix, Pelargonium sidoides, Sambucus nigra, Thymus vulgaris, hyaluronic acid, and saline solutions. However, further rigorous studies should confirm natural products' efficacy and safety to relieve PAC.

Preparation and characterization of poly (lactic-co-glycolic acid) nanofibers containing simvastatin coated with hyaluronic acid for using in periodontal tissue engineering.

Periodontal diseases can lead to soft tissue defects. Tissue engineering can provide functional replacements for damaged tissues. Recently, electrospun nanofibers have attracted great interest for tissue engineering and drug delivery applications. This has been revealed that statins exhibit positive impacts on the proliferation and regeneration of periodontal tissues. Electrospun simvastatin loaded poly (lactic-co-glycolic acid) (SIM-PLGA-NF) were prepared using electrospinning technique. Optimal conditions for preparation of SIM-PLGA-NF (PLGA concentration of 30 wt%, voltage of 15 kV, and flow rate of 1.5ml h-1 ) were identified using a 23 factorial design. The optimized SIM-PLGA-NFs (diameter of 640.2 ± 32.5nm and simvastatin entrapment efficacy of 99.6 ± 1.5%) were surface modified with 1% w/v hyaluronic acid solution (1%HA- SIM-PLGA-NF) to improve their compatibility with fibroblasts and potential application as a periodontal tissue engineering scaffold. HA-SIM-PLGA NFs were analyzed using SEM, FTIR, and XRD. 1%HA-SIM-PLGA-NF had uniform, bead-free and interwoven morphology, which is similar to the extracellular matrix. The mechanical performance of SIM-PLGA-NFs and release profile of simvastatin from these nanofibers have been also greatly improved after coating with HA. In vitro cellular tests showed that the proliferation, adhesion, and differentiation of fibroblast cells positively enhanced on the surface of 1%HA- SIM-PLGA-NF. These results demonstrate the potential application of 1%HA-SIM-PLGA-NFs as a scaffold for periodontal tissue engineering.

Novel injectable needle-type knife, ProKnife for colorectal endoscopic submucosal dissection.

Watch a video of this article. Although time-consuming, which may be partly attributable to the need to change devices for local injection, colorectal endoscopic submucosal dissection (ESD) is a valuable procedure.1 To overcome this problem, a water jet function has been developed;2 however, most devices deliver water from the base of the electrode rather than the tip. A novel injectable needle-type knife (ORISE ProKnife; Boston Scientific, Tokyo, Japan) has recently become available (Fig. 1A). The electrode shaft has a 0.5-mm diameter (Fig. 1B, arrow a), and the T-shaped tip has a 0.81-mm diameter (arrow b) with 0.15-mm thickness (arrow c). It provides excellent hemostasis in addition to enabling incision and dissection. A significant advantage is the large injection lumen diameter (0.3 mm) of the electrode, which is twice larger than that of an existing device, the HybridKnife. It allows the local injection of fluids, such as highly viscous hyaluronic acid preparations. Direct focal injection from the center of the needle tip provides a sustained lift without changing the device (Fig. 1C). Furthermore, the device handle has a cleaning tool to clear the lumen and re-inject once clogging occurs during the procedure (Video S1). Colonoscopy revealed a non-granular-pseudo-depressed 30-mm laterally spreading tumor in the splenic flexure (Fig. 2A). Initial submucosal lifting with hyaluronic acid solution stained with indigo-carmine was performed using a standard injection needle. Using ProKnife, a local injection of hyaluronic acid was administered while performing mucosal incision and submucosal dissection (Fig. 2B,C). Despite the poor maneuverability, ProKnife completed the ESD in 30 min without changing the device (Fig. 2D). ProKnife was able to consistently administer submucosal injections from the center of the needle tip, which enabled reliable lifting of the submucosa and improved the visibility of the dissecting plane during the procedure. The knife is a novel, efficacious time-saving surgical device. Authors declare no conflict of interest for this article. We would like to thank Mayuko Namioka for video editing and Takefumi Kikuchi and Shotaro Kawamura for the helpful discussion. We also would like to thank Editage (www.editage.com) for English language editing. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Stability and Diffusion Properties of Insulin in Dissolvable Microneedles: A Multiscale Simulation Study

Microneedle (MN) technology has been proven to be promising to become an effective drug delivery route of insulin for diabetes treatment, with the advantages of high delivery efficiency, convenient management, and minimal risk of infection. However, efforts are still required to verify the insulin activity in MNs for further clinical application. Moreover, it is also essential to study the diffusion properties of insulin to understand the ability of various MN materials to control insulin release. Herein, we have combined all-atom molecular dynamics simulation and coarse-grained dissipative particle dynamics to systematically study insulin's structural stability and diffusion coefficient in polyvinyl alcohol and hyaluronic acid solutions. The all-atom simulation reveals the dissimilarities in the interaction mode between insulin and the two polymers. It also points out that the presence of the two polymers would not irreversibly impact the secondary structure of insulin, thereby ensuring regular insulin expression in vivo. Mesoscopic simulation results manifest that the diffusion coefficient of insulin in hyaluronic acid (HA) solution is greater than that of the polyvinyl alcohol (PVA) system. Meanwhile, through the study of insulin centroid trajectory, we have claimed two different diffusion mechanisms of insulin in polymer solution: The movement of insulin in the HA and water solution follows the Brownian motion rule. In comparison, the hopping effect of insulin has been observed in the PVA solution due to poor intermolecular affinity as well as lower polymer water solubility. By summarizing different diffusion mechanisms, this study can provide theoretical guidance for preparing insulin-loaded dissolvable MNs.