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Sample records for hyaluronic acid volumizing

  1. Ultrasound and Histologic Examination after Subcutaneous Injection of Two Volumizing Hyaluronic Acid Fillers: A Preliminary Study

    PubMed Central

    Besse, Stéphanie; Sarazin, Didier; Quinodoz, Pierre; Elias, Badwi; Safa, Marva; Vandeputte, Joan

    2017-01-01

    Background: This study examined the influence of hyaluronic acid (HA) crosslinking technology on the ultrasound and histologic behavior of HA fillers designed for subcutaneous injection. Methods: One subject received subcutaneous injections of 0.25 ml Cohesive Polydensified Matrix (CPM) and Vycross volumizing HA in tissue scheduled for abdominoplasty by bolus and retrograde fanning techniques. Ultrasound analyses were performed on days 0 and 8 and histologic analyses on days 0 and 21 after injection. A series of simple rheologic tests was also performed. Results: Day 0 ultrasound images after bolus injection showed CPM and Vycross as hypoechogenic papules in the hypodermis. CPM appeared little changed after gentle massage, whereas Vycross appeared more hyperechogenic and diminished in size. Ultrasound images at day 8 were similar. On day 0, both gels appeared less hypoechogenic after retrograde fanning than after bolus injection. Vycross was interspersed with hyperechogenic areas (fibrous septa from the fat network structure) and unlike CPM became almost completely invisible after gentle massage. On day 8, CPM appeared as a hypoechogenic pool and Vycross as a long, thin rod. Day 0 histologic findings confirmed ultrasound results. Day 21 CPM histologic findings showed a discrete inflammatory reaction along the injection row after retrograde fanning. Vycross had a more pronounced inflammatory reaction, particularly after retrograde fanning, with macrophages and giant cells surrounding the implant. Rheologic tests showed CPM to have greater cohesivity and resistance to traction forces than Vycross. Conclusions: CPM HA volumizer appears to maintain greater tissue integrity than Vycross after subcutaneous injection with less inflammatory activity. PMID:28280664

  2. Beneficial effects of hyaluronic acid.

    PubMed

    Sudha, Prasad N; Rose, Maximas H

    2014-01-01

    Biomaterials are playing a vital role in our day-to-day life. Hyaluronan (hyaluronic acid), a biomaterial, receives special attention among them. Hyaluronic acid (HA) is a polyanionic natural polymer occurring as linear polysaccharide composed of glucuronic acid and N-acetylglucosamine repeats via a β-1,4 linkage. It is the most versatile macromolecule present in the connective tissues of all vertebrates. Hyaluronic acid has a wide range of applications with its excellent physicochemical properties such as biodegradability, biocompatibility, nontoxicity, and nonimmunogenicity and serves as an excellent tool in biomedical applications such as osteoarthritis surgery, ocular surgery, plastic surgery, tissue engineering, and drug delivery. It plays a key role in cushioning and lubricating the body and is abundant in the eyes, joints, and heart valves. A powerful antioxidant, hyaluronic acid is perhaps best known for its ability to bond water to tissue. Hyaluronan production increases in proliferating cells, and the polymer may play a role in mitosis. This chapter gives an overview of hyaluronic acid and its physicochemical properties and applications. This chapter gives a deep understanding on the special benefits of hyaluronic acid in the fields of pharmaceutical, medical, and environmental applications. Hyaluronic acid paves the way for beneficial research and applications to the welfare of life forms.

  3. Hyaluronic acid and tendon lesions

    PubMed Central

    Kaux, Jean-François; Samson, Antoine; Crielaard, Jean-Michel

    2015-01-01

    Summary Introduction recently, the viscoelastic properties of hyaluronic acid (HA) on liquid connective tissue have been proposed for the treatment of tendinopathies. Some fundamental studies show encouraging results on hyaluronic acid’s ability to promote tendon gliding and reduce adhesion as well as to improve tendon architectural organisation. Some observations also support its use in a clinical setting to improve pain and function. This literature review analyses studies relating to the use of hyaluronic acid in the treatment of tendinopathies. Methods this review was constructed using the Medline database via Pubmed, Scopus and Google Scholar. The key words hyaluronic acid, tendon and tendinopathy were used for the research. Results in total, 28 articles (in English and French) on the application of hyaluronic acid to tendons were selected for their relevance and scientific quality, including 13 for the in vitro part, 7 for the in vivo animal part and 8 for the human section. Conclusions preclinical studies demonstrate encouraging results: HA permits tendon gliding, reduces adhesions, creates better tendon architectural organisation and limits inflammation. These laboratory observations appear to be supported by limited but encouraging short-term clinical results on pain and function. However, controlled randomised studies are still needed. PMID:26958533

  4. [Injection treatment with hyaluronic acid].

    PubMed

    Jerosch, J

    2015-11-01

    This article presents the spectrum of indications for the use of hyaluronic acid (HA) based on the recommendations of the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), the Osteoarthritis Research Society International (OARSI), the International Institute for Health and Clinical Excellence (NICE) and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) taking the reality of patient care in Europe into account.

  5. Hyaluronic acid concentration in liver diseases.

    PubMed

    Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

    2016-11-01

    The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.

  6. Temporal fossa defects: techniques for injecting hyaluronic acid filler and complications after hyaluronic acid filler injection.

    PubMed

    Juhász, Margit Lai Wun; Marmur, Ellen S

    2015-09-01

    Facial changes with aging include thinning of the epidermis, loss of skin elasticity, atrophy of muscle, and subcutaneous fat and bony changes, all which result in a loss of volume. As temporal bones become more concave, and the temporalis atrophies and the temporal fat pad decreases, volume loss leads to an undesirable, gaunt appearance. By altering the temporal fossa and upper face with hyaluronic acid filler, those whose specialty is injecting filler can achieve a balanced and more youthful facial structure. Many techniques have been described to inject filler into the fossa including a "fanned" pattern of injections, highly diluted filler injection, and the method we describe using a three-injection approach. Complications of filler in the temporal fossa include bruising, tenderness, swelling, Tyndall effect, overcorrection, and chewing discomfort. Although rare, more serious complications include infection, foreign body granuloma, intravascular necrosis, and blindness due to embolization into the ophthalmic artery. Using reversible hyaluronic acid fillers, hyaluronidase can be used to relieve any discomfort felt by the patient. Injectors must be aware of the complications that may occur and provide treatment readily to avoid morbidities associated with filler injection into this sensitive area.

  7. Hyaluronic acid: Hope of light to black triangles

    PubMed Central

    Tanwar, Jyotsana; Hungund, Shital A.

    2016-01-01

    Interdental papilla construction, especially in the esthetic area, is one of the most challenging tasks. Interdental papilla loss might occur due to several reasons as a consequence of periodontal surgery or trauma. The purpose of this study is to report the reconstruction of lost interdental papilla using hyaluronic acid gel. Hyaluronic acid is a glycosaminoglycan molecule with anti-inflammatory, anti-edematous properties on periodontal tissues invaded by submicrobial flora. It enhances wound healing and accelerates periodontal repair and regeneration. In addition to the field of dentistry, it has been used in other fields such as orthopedics, ophthalmology, and dermatology. It shows growth factor interaction, regulates osmotic pressure, and enhances tissue lubrication, which helps in maintaining the structural and homeostatic integrity of tissues, hence resulting in beneficial effect on lost interdental papilla. This study was aimed to reconstruct the lost interdental papilla by injecting 0.2% hyaluronic acid via nonsurgical approach. It is a noninvasive approach which reduces patient's postoperative discomfort with marked variations in the volume of interdental papilla before and after the procedure. As sufficient information is not available regarding the effectiveness of hyaluronic acid in interdental papilla construction, this study was conducted. PMID:27891319

  8. The Hyaluronic Acid Fillers: Current Understanding of the Tissue Device Interface.

    PubMed

    Greene, Jacqueline J; Sidle, Douglas M

    2015-11-01

    The article is a detailed update regarding cosmetic injectable fillers, specifically focusing on hyaluronic acid fillers. Hyaluronic acid-injectable fillers are used extensively for soft tissue volumizing and contouring. Many different hyaluronic acid-injectable fillers are available on the market and differ in terms of hyaluronic acid concentration, particle size, cross-linking density, requisite needle size, duration, stiffness, hydration, presence of lidocaine, type of cross-linking technology, and cost. Hyaluronic acid is a natural component of many soft tissues, is identical across species minimizing immunogenicity has been linked to wound healing and skin regeneration, and is currently actively being studied for tissue engineering purposes. The biomechanical and biochemical effects of HA on the local microenvironment of the injected site are key to its success as a soft tissue filler. Knowledge of the tissue-device interface will help guide the facial practitioner and lead to optimal outcomes for patients.

  9. Efficacy and durability of hyaluronic acid fillers for malar enhancement: a prospective, randomized, spilt-face clinical controlled trial.

    PubMed

    Jeong, Ki Heon; Gwak, Min Jae; Moon, Sung Kyung; Lee, Sang Jun; Shin, Min Kyung

    2017-01-31

    Various hyaluronic acid fillers can be used for facial attenuation and rejuvenation. The efficacy and durability of hyaluronic acid fillers are of major concern to dermatologists and patients. This study aimed to evaluate three dimensional morphology, tissue distribution, and changes in volume after injection of two different hyaluronic acid fillers. Ten Korean women were enrolled in this study. Each subject was injected with monophasic hyaluronic acid filler in one malar area and biphasic filler in the other. Clinical outcome was measured before and after injection, and after 2, 4, 6, 8, 12, and 24 weeks, using the Global Aesthetic Improvement Scale, photographs and Moire's topography. Facial magnetic resonance imaging (MRI) was performed twice over six months. Both products showed good results after injection and demonstrated good durability over time. MRI was a useful modality for assessing tissue distribution and volume changes. The effects and durability after injection of monophasic hyaluronic acid filler and biphasic hyaluronic acid filler are generally comparable.

  10. Chemical Synthesis of a Hyaluronic Acid Decasaccharide

    PubMed Central

    Lu, Xiaowei; Kamat, Medha N.; Huang, Lijun; Huang, Xuefei

    2009-01-01

    The chemical synthesis of a hyaluronic acid decasaccharide using the pre-activation based chemoselective glycosylation strategy is described. Assembly of large oligosaccharides is generally challenging due to the increased difficulties in both glycosylation and deprotection. Indeed, the same building blocks previously employed for hyaluronic acid hexasaccharide syntheses failed to yield the desired decasaccharide. After extensive experimentation, the decasaccharide backbone was successfully constructed with an overall yield of 37% from disaccharide building blocks. The trichloroacetyl group was used as the nitrogen protective group for the glucosamine units and the addition of TMSOTf was found to be crucial to suppress the formation of trichloromethyl oxazoline side-product and enable high glycosylation yield. For deprotections, the combination of a mild basic condition and the monitoring methodology using 1H-NMR allowed the removal of all base-labile protective groups, which facilitated the generation of the fully deprotected HA decasaccharide. PMID:19764799

  11. Dietary Hyaluronic Acid Migrates into the Skin of Rats

    PubMed Central

    Mitsugi, Koichi; Odanaka, Wataru; Seino, Satoshi; Masuda, Yasunobu

    2014-01-01

    Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid). 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered 14C-hyaluronic acid was found in the blood. Approximately 90% of 14C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week) after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine. PMID:25383371

  12. [Serum hyaluronic acid in osteoarthritis].

    PubMed

    Balblanc, J C; Hartmann, D; Noyer, D; Mathieu, P; Conrozier, T; Tron, A M; Piperno, M; Richard, M; Vignon, E

    1993-03-01

    In this prospective study, serum hyaluronate (SH) was assayed using a radiometric method (Pharmacia) in 73 osteoarthritis patients and 39 controls. All assays were performed between 8 h 00 and 9 h 00 a.m. because SH levels exhibit circadian variations. SH levels were significantly higher in patients with osteoarthritis than in controls (92 +/- 66 micrograms/l and 39 +/- 21 micrograms/l, respectively, p = 0.0001). Among 50 patients with osteoarthritis, including 29 with knee involvement and 21 with hip involvement, SH levels were not correlated with morning stiffness, duration of symptoms, Lequesne's algofunctional index, erythrocyte sedimentation rate, C-reactive protein, severity of roentgenographic changes in the affected knee or hip, disease extension, or severity. The lack of any relationship between changes in SH levels and Lequesne's is index values in 25 patients or between SH levels and joint space narrowing evaluated retrospectively in 16 patients, as well as the prompt return to high SH levels after arthroplasty and synovectomy in 14 patients with hip joint osteoarthritis, suggest that this potential marker is not useful for monitoring osteoarthritis in a single joint.

  13. Physics of soft hyaluronic acid-collagen type II double network gels

    NASA Astrophysics Data System (ADS)

    Morozova, Svetlana; Muthukumar, Murugappan

    2015-03-01

    Many biological hydrogels are made up of multiple interpenetrating, charged components. We study the swelling, elastic diffusion, mechanical, and optical behaviors of 100 mol% ionizable hyaluronic acid (HA) and collagen type II fiber networks. Dilute, 0.05-0.5 wt% hyaluronic acid networks are extremely sensitive to solution salt concentration, but are stable at pH above 2. When swelled in 0.1M NaCl, single-network hyaluronic acid gels follow scaling laws relevant to high salt semidilute solutions; the elastic shear modulus G' and diffusion constant D scale with the volume fraction ϕ as G' ~ϕ 9 / 4 and D ~ϕ 3 / 4 , respectively. With the addition of a collagen fiber network, we find that the hyaluronic acid network swells to suspend the rigid collagen fibers, providing extra strength to the hydrogel. Results on swelling equilibria, elasticity, and collective diffusion on these double network hydrogels will be presented.

  14. HYALURONIC ACID IN DERMAL REJUVENATION: AN IN VITRO STUDY.

    PubMed

    Avantaggiato, A; Pascali, M; Lauritano, D; Cura, F; Pezzetti, F; Palmieri, A

    2015-01-01

    The purpose of this paper is to evaluate the role of hyaluronic acid in bio-revitalization by testing several extracellular matrix biological parameters in cultured dermal fibroblasts. To this aim, fibroblastic expressed genes after exposition to three hyaluronic acid medical devices were evaluated. Cells were seeded on a layer of three different medical devices containing 6.2, 10 and 20 mg/ml of hyaluronic acid for 24 h. Real Time Polymerase Chain Reaction was performed to investigate gene expressions. Genes encoding hyaluronic acid synthesis and degradation, Metalloproteinases 2 and 3 and Desmoplakin production as well as GDF6, and IGF1 were activated by hyaluronic acid products. The in vitro study showed similar effects on tested genes despite a different concentration of hyaluronic acid contained in the medical devices and the simultaneous presence of other additives. Based on the reported data, gene activations are an aspect of metabolic modulation of signalling pathways rather than the proportional production of a specific connective tissue molecule. Indeed different hyaluronic acid concentration and the presence of other additives did not change the overall effect on the studied genes. We believe that the optimization of extracellular matrix micro-environment, obtained by enhanced structural support with hyaluronic acid, leads to functional and metabolic improvement.

  15. Human glans penis augmentation using injectable hyaluronic acid gel.

    PubMed

    Kim, J J; Kwak, T I; Jeon, B G; Cheon, J; Moon, D G

    2003-12-01

    Although augmentation phalloplasty is not an established procedure, some patients still need enlargement of their penis. Current penile augmentation is girth enhancement of penile body by dermofat graft. We performed this study to identify the efficacy and the patient's satisfaction of human glans penis augmentation with injectable hyaluronic acid gel. In 100 patients of subjective small penis (Group I) and 87 patients of small glans after dermofat graft (Group II), 2 cm(3) of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1 y after injection, changes of glandular diameter were measured by tapeline. Patient's visual estimation of glandular size (Gr 0-4) and patient's satisfaction (Grade (Gr) 0-4) were evaluated, respectively. Any adverse reactions were also evaluated. The mean age of patients was 42.2 (30-70) y in Group I and 42.13 (28-61) y in Group II. The maximal glandular circumference was significantly increased compared to basal circumference of 9.13+/-0.64 cm in Group I (P<0.01) and 9.49+/-1.05 cm in Group II (P<0.01) at 1 y after injection. Net increase of maximal glandular circumference after glans augmentation was 14.93+/-0.80 mm in Group I and 14.78+/-0.89 mm in Group II. In patient's visual estimation, more than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and 69% in Group II. There was no abnormal reaction in area feeling, texture, and color. In most cases, initial discoloration by glandular swelling recovered to normal within 2 weeks. There were no signs of inflammation and no serious adverse reactions in all cases. These results suggest that injectable hyaluronic acid gel is a safe and effective material for augmentation of glans penis.

  16. Rheology and lubricity of hyaluronic acid

    NASA Astrophysics Data System (ADS)

    Liang, Jing; Krause, Wendy E.

    2007-03-01

    The polyelectrolyte hyaluronic acid (HA, hyaluronan) is an important component in synovial fluid (i.e., the fluid that lubricates our freely moving joints). Its presence results in highly viscoelastic solutions. In comparison to healthy synovial fluid, diseased fluid has a reduced viscosity and loss of lubricity. In osteoarthritis the reduction in viscosity results from a decline in both the molecular weight and concentration of HA. In our investigation, we attempt to correlate the rheological properties of HA solutions to changes in lubrication and wear. A nanoindenter will be used to evaluate the coefficient of friction and wear properties between the nanoindenter tip and ultrahigh molecular weight polyethylene in both the presence and absence of a thin film of HA solution.

  17. Editorial Commentary: Knee Hyaluronic Acid Viscosupplementation Reduces Osteoarthritis Pain.

    PubMed

    Lubowitz, James H

    2015-10-01

    In contrast to the AAOS knee osteoarthritis guidelines, systematic review of overlapping meta-analyses shows that viscosupplementation with intra-articular hyaluronic acid injection reduces knee osteoarthritis pain and improves function according to the highest level of evidence.

  18. Hyaluronic acid viscosupplementation and osteoarthritis: current uses and future directions.

    PubMed

    Strauss, Eric J; Hart, Jennifer A; Miller, Mark D; Altman, Roy D; Rosen, Jeffrey E

    2009-08-01

    Intra-articular hyaluronic acid viscosupplementation is gaining popularity as a treatment option in the nonoperative management of patients with osteoarthritis. Recent clinical studies have demonstrated that the anti-inflammatory, anabolic, and chondroprotective actions of hyaluronic acid reduce pain and improve patient function. With evidence mounting in support of the efficacy of this treatment modality for patients with osteoarthritis, its potential use in additional patient populations and for other pathologies affecting the knee is being investigated. The current article reviews the use of intra-articular hyaluronic acid viscosupplementation in the management of knee osteoarthritis and presents the potential for expanding its indications for other joints and alternative patient subpopulations. Additionally, future directions for the use of hyaluronic acid and areas of active research are discussed.

  19. The tower technique: a novel technique for the injection of hyaluronic acid fillers.

    PubMed

    Bartus, Cynthia L; Sattler, Gerhard; Hanke, C William

    2011-11-01

    A number of injection techniques have been described for the placement of hyaluronic acid fillers. Such techniques include, but are not limited to, linear threading, depot, fanning, and layering. The tower technique for hyaluronic acid filler injection is a novel variation of the depot and layering techniques. With this technique, the hyaluronic acid is deposited via a perpendicular approach to the deep tissue plane with a gradual tapering of product deposition as the needle is withdrawn. A series of towers or struts are thus created. These towers serve as support structures for the overlying soft tissue, thereby restoring the face to a more youthful appearance. The anatomic areas most amenable to this technique include the lateral brow, the nasolabial folds, the marionette lines, the prejowl sulcus, and the mental region. A detailed description of the tower technique for facial volume restoration with hyaluronic acid fillers is provided. Further prospective studies are needed to compare the efficacy, safety, and longevity of this technique to other commonly used techniques for the injection of hyaluronic acid fillers.

  20. Determination of the presence of hyaluronic acid in preparations containing amino acids: the molecular weight characterization.

    PubMed

    Bellomaria, A; Nepravishta, R; Mazzanti, U; Marchetti, M; Piccioli, P; Paci, M

    2014-10-15

    Several pharmaceutical preparations contain hyaluronic acid in the presence of a large variety of low molecular weight charged molecules like amino acids. In these mixtures, it is particularly difficult to determine the concentration and the molecular weight of the hyaluronic acid fragments. In fact zwitterionic compounds in high concentration behave by masking the hyaluronic acid due to the electrostatic interactions between amino acids and hyaluronic acid. In such conditions the common colorimetric test of the hyaluronic acid determination appears ineffective and in the (1)H NMR spectra the peaks of the polymer disappear completely. By a simple separation procedure the presence of hyaluronic acid was revealed by the DMAB test and (1)H NMR while its average molecular weight in the final product was determined by DOSY NMR spectroscopy alone. The latter determination is very important due to the healthy effects of some sizes of this polymer's fragments.

  1. Electrostatic effects on hyaluronic acid configuration

    NASA Astrophysics Data System (ADS)

    Berezney, John; Saleh, Omar

    2015-03-01

    In systems of polyelectrolytes, such as solutions of charged biopolymers, the electrostatic repulsion between charged monomers plays a dominant role in determining the molecular conformation. Altering the ionic strength of the solvent thus affects the structure of such a polymer. Capturing this electrostatically-driven structural dependence is important for understanding many biological systems. Here, we use single molecule manipulation experiments to collect force-extension behavior on hyaluronic acid (HA), a polyanion which is a major component of the extracellular matrix in all vertebrates. By measuring HA elasticity in a variety of salt conditions, we are able to directly assess the contribution of electrostatics to the chain's self-avoidance and local stiffness. Similar to recent results from our group on single-stranded nucleic acids, our data indicate that HA behaves as a swollen chain of electrostatic blobs, with blob size proportional to the solution Debye length. Our data indicate that the chain structure within the blob is not worm-like, likely due to long-range electrostatic interactions. We discuss potential models of this effect.

  2. Complications and management of breast enhancement using hyaluronic acid.

    PubMed

    Ishii, Hidenori; Sakata, Kazuaki

    2014-01-01

    The authors report on their experience with using hyaluronic acid of non-animal origin manufactured using commercially available technology (Macrolane, Q-Med AB, Sweden) for breast enhancement in 4000 women treated since 2004 and describe the most common complications and their successful treatment. On average, 30 mL to 40 mL of Macrolane was injected into each breast. Of 274 women who returned to the clinic during 2007, <10% experienced local adverse events (eg, gel dislocation, Macrolane nodules and rare cases of infection). There were no serious systemic events and treatment was well tolerated. To prevent local complications, such as infection, an aseptic injection technique was required and early treatment of adverse events is recommended. While only small volumes of Macrolane were injected, it is comparatively easy and safe to perform breast enhancement of up to one cup size to correct asymmetry between breasts and to create fullness in the upper portion of the breast.

  3. Comprehensive Treatment of Periorbital Region with Hyaluronic Acid

    PubMed Central

    Rocha, Camila Roos Mariano Da; Bastos, Julien Toni De; Silva, Priscila Mara Chaves e

    2015-01-01

    The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients. PMID:26155325

  4. Physical properties of crosslinked hyaluronic acid hydrogels.

    PubMed

    Collins, Maurice N; Birkinshaw, Colin

    2008-11-01

    In order to improve the mechanical properties and control the degradation rate of hyaluronic acid (HA) an investigation of the structural and mechanical properties of the hydrogels crosslinked using divinyl sulfone (DVS), glutaraldehyde (GTA) and freeze-thawing, or autocrosslinking has been carried out. The thermal and mechanical properties of the gels were characterised by differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and compression tests. The solution degradation products of each system have been analysed using size exclusion chromatography (SEC) and the Zimm-Stockmayer theory applied. Autocrosslinked gels swell the most quickly, whereas the GTA crosslinked gels swell most slowly. The stability of the autocrosslinked gels improves with a reduction in solution pH, but is still poor. GTA and DVS crosslinked gels are robust and elastic when water swollen, with glass transition values around 20 degrees C. SEC results show that the water soluble degradation products of the gels show a reduction in the radius of gyration at any particular molecular weight and this is interpreted as indicating increased hydrophobicity arising from chemical modification.

  5. Biocompatible, hyaluronic acid modified silicone elastomers.

    PubMed

    Alauzun, Johan G; Young, Stuart; D'Souza, Renita; Liu, Lina; Brook, Michael A; Sheardown, Heather D

    2010-05-01

    Although silicones possess many useful properties as biomaterials, their hydrophobicity can be problematic. To a degree, this issue can be addressed by surface modification with hydrophilic polymers such as poly(ethylene glycol), but the resulting structures are usually not conducive to cell growth. In the present work, we describe the synthesis and characterization of covalently linked hyaluronic acid (HA) (35 kDa) to poly(dimethylsiloxane) (PDMS) elastomer surfaces. HA is of interest because of its known biological properties; its presence on a surface was expected to improve the biocompatibility of silicone materials for a wide range of bioapplications. HA was introduced with a coupling agent in two steps from high-density, tosyl-modified, poly(ethylene glycol) tethered silicone surfaces. All materials synthesized were characterized by water contact angle, ATR-FTIR, XPS and (13)C solid state NMR spectroscopy. Biological interactions with these modified silicone surfaces were assessed by examining interactions with fibrinogen as a model protein as well as determining the in vitro response of fibroblast (3T3) and human corneal epithelial cells relative to unmodified poly(dimethylsiloxane) controls. The results suggest that HA modification significantly enhances cell interactions while decreasing protein adsorption and may therefore be effective for improving biocompatibility of PDMS and other materials.

  6. Hyaluronic Acid Hydrogels for Biomedical Applications

    PubMed Central

    Burdick, Jason A.; Prestwich, Glenn D.

    2013-01-01

    Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms -- viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids -- for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications. PMID:21394792

  7. Extracellular depolymerization of hyaluronic acid in cultured human skin fibroblasts

    SciTech Connect

    Nakamura, T.; Takagaki, K.; Kubo, K.; Morikawa, A.; Tamura, S.; Endo, M. )

    1990-10-15

    The chain length of ({sup 3}H)hyaluronic acid synthesized by cultivating human skin fibroblasts in the presence of ({sup 3}H)glucosamine was investigated. ({sup 3}H)Hyaluronic acid obtained from the matrix fraction was excluded from a Sepharose CL-2B column irrespective of the incubation period, whereas that from the medium was depolymerized into a constant chain length (Mr = 40,000). The reducing and non-reducing terminals of the depolymerized hyaluronic acid were N-acetylglucosamine and glucuronic acid, respectively. Prolonged incubation produced no oligosaccharides as shown by examination of hyaluronidase digests, suggesting the presence of a novel endo-beta-N-acetylglucosaminidase in cultured human skin fibroblasts.

  8. Preactivated hyaluronic acid: A potential mucoadhesive polymer for vaginal delivery.

    PubMed

    Nowak, Jessika; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2015-01-15

    The objective of this study was to develop mucoadhesive polymeric excipients for vaginal drug delivery systems. Hyaluronic acid was thiolated and subsequently preactivated with 6-mercaptonicotinamide (HA-CYS-MNA) to enhance stability and mucoadhesive properties on vaginal mucosa. After determination of the thiol group content, disintegration studies and in vitro mucoadhesion studies (rotating cylinder and tensile) were performed. Furthermore, swelling behavior and cytotoxicity studies were performed in comparison with corresponding polymers. Both, disintegration and in vitro mucoadhesive studies revealed that modifying HA-CYS with MNA resulted in higher stability (3.6-fold prolonged disintegration time compared to unmodified hyaluronic acid) and prolonged mucoadhesion time. MTT assay and LDH revealed no toxicity for the polymeric excipients and safe for their use. Disintegration and swelling results conducted more pronounced stability of the preactivated thiomers compared to corresponding unmodified ones. According to these results preactivated hyaluronic acid might be a useful tool for vaginal delivery systems.

  9. Hyaluronic acid for anticancer drug and nucleic acid delivery.

    PubMed

    Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

    2016-02-01

    Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results.

  10. Hyaluronic acid content of deep and subcutaneous bursae of man.

    PubMed Central

    Canoso, J J; Stack, M T; Brandt, K D

    1983-01-01

    To provide a comparison of the contents of subcutaneous and deep bursae we dissected these structures from unfixed cadavers without apparent joint disease. No free fluid was found within any olecranon or prepatellar bursae (examples of subcutaneous bursae), while viscous fluid was invariably present in the (deep) retrocalcaneal bursae. The hyaluronic acid content of the washings of 5 rectrocalcaneal bursae ranged from 142 to 591 nmol hexosamine (mean = 281 nmol hexosamine). In contrast, the hyaluronic acid content of 4 olecranon bursae was much lower (range 35-72 nmol, mean 53 nmol hexosamine), and hyaluronate was not detected in washings from either of 2 prepatellar bursae. The greater hyaluronate content of the retrocalcaneal bursae did not appear to be due to a greater surface area, since on the basis of calculations made from plaster casts the surface areas of the olecranon and prepatellar bursae were approximately 3 times and 2 times, respectively, greater than that of the retrocalcaneal bursae. The data suggest that, although hyaluronic acid may lubricate deep bursae, other factors may be more important in reducing friction within superficial bursae. Images PMID:6847262

  11. Hyaluronic Acid--an "Old" Molecule with "New" Functions: Biosynthesis and Depolymerization of Hyaluronic Acid in Bacteria and Vertebrate Tissues Including during Carcinogenesis.

    PubMed

    Tsepilov, R N; Beloded, A V

    2015-09-01

    Hyaluronic acid is an evolutionarily ancient molecule commonly found in vertebrate tissues and capsules of some bacteria. Here we review modern data regarding structure, properties, and biological functions of hyaluronic acid in mammals and Streptococcus spp. bacteria. Various aspects of biogenesis and degradation of hyaluronic acid are discussed, biosynthesis and degradation metabolic pathways for glycosaminoglycan together with involved enzymes are described, and vertebrate and bacterial hyaluronan synthase genes are characterized. Special attention is given to the mechanisms underlying the biological action of hyaluronic acid as well as the interaction between polysaccharide and various proteins. In addition, all known signaling pathways involving hyaluronic acid are outlined. Impaired hyaluronic acid metabolism, changes in biopolymer molecular weight, hyaluronidase activity, and enzyme isoforms often accompany carcinogenesis. The interaction between cells and hyaluronic acid from extracellular matrix that may be important during malignant change is discussed. An expected role for high molecular weight hyaluronic acid in resistance of naked mole rat to oncologic diseases and the protective role of hyaluronic acid in bacteria are discussed.

  12. Preparation of low-molecular-weight hyaluronic acid by ozone treatment.

    PubMed

    Wu, Yue

    2012-06-20

    Recently, low-molecular-weight hyaluronic acid has been reported to have novel features, such as free radical scavenging activities, antioxidant activities, promotion of excisional wound healing, etc. In the present work, degradation of native hyaluronic acid by ozone treatment was performed for preparation of low-molecular-weight hyaluronic acid. The molecular weight of native hyaluronic acid was reduced from 1535 to 87 kDa for 120 min at 40°C. The rate of reduction of molecular weight was 94.33%. The FT-IR, 13C NMR, and UV-vis spectra suggested that there was no obvious modification of chemical structure of low-molecular-weight hyaluronic acid. The use of degradation of native hyaluronic acid by ozone treatment can be a useful alternative for production of low-molecular-weight hyaluronic acid.

  13. Effect of hyaluronic acid molecular weight on the morphology of quantum dot-hyaluronic acid conjugates.

    PubMed

    Kim, Jiseok; Park, Kitae; Hahn, Sei Kwang

    2008-01-01

    The morphological analysis of novel quantum dot-hyaluronic acid (QDot-HA) conjugates was carried out with a transmission electron microscope (TEM). Adipic acid dihydrazide-modified HA (HA-ADH) was synthesized and conjugated to quantum dots (QDots) having carboxyl terminal ligands which were activated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS). HA molecules with a molecular weight (MW) of 20K, 234 K and 3000 K were used to investigate the effect of MW on the morphology of QDot-HA conjugates. The TEM micrographs of QDot-HA conjugates showed branched and multi-layered chain type morphology formed by inter- and intra-molecular conjugation of QDots to HA molecules. The size of QDot-HA conjugate increased with the MW of HA. QDot-HA conjugate could be successfully used for real-time bio-imaging of HA derivatives in nude mice. The novel QDot-HA conjugate will be further used to investigate the biological roles of HA with a different MW in the body.

  14. Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads

    NASA Astrophysics Data System (ADS)

    Kim, Jin-Tae; Lee, Deuk Yong; Kim, Tae-Hyung; Song, Yo-Seung; Cho, Nam-Ihn

    2014-05-01

    Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity ( in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.

  15. In situ forming hydrogel composed of hyaluronate and polygalacturonic acid for prevention of peridural fibrosis.

    PubMed

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Liu, Tse-Ying; Chen, Ming-Hong

    2015-04-01

    Hyaluronic acid-based hydrogels can reduce postoperative adhesion. However, the long-term application of hyaluronic acid is limited by tissue mediated enzymatic degradation. To overcome this limitation, we developed a polygalacturonic acid and hyaluronate composite hydrogel by Schiff's base crosslinking reaction. The polygalacturonic acid and hyaluronate composite hydrogels had short gelation time (less than 15 s) and degraded by less than 50 % in the presence of hyaluronidase for 7 days. Cell adhesion and migration assays showed polygalacturonic acid and hyaluronate composite hydrogels prevented fibroblasts from adhesion and infiltration into the hydrogels. Compared to hyaluronate hydrogels and commercial Medishield™ gels, polygalacturonic acid and hyaluronate composite hydrogel was not totally degraded in vivo after 4 weeks. In the rat laminectomy model, polygalacturonic acid and hyaluronate composite hydrogel also had better adhesion grade and smaller mean area of fibrous tissue formation over the saline control and hyaluronate hydrogel groups. Polygalacturonic acid and hyaluronate composite hydrogel is a system that can be easy to use due to its in situ cross-linkable property and potentially promising for adhesion prevention in spine surgeries.

  16. Selective dermal rejuvenation using intradermal injection of carbon dioxide and hyaluronic acid for facial wrinkles.

    PubMed

    Chin, Sae Hoon; Burm, Jin Sik; Kim, Youn Wha

    2013-06-01

    This study assessed selective dermal rejuvenation using sequential intradermal injections of carbon dioxide and hyaluronic acid as a treatment of facial wrinkles. An injection device was designed. After topical anesthesia, 0.1-mL carbon dioxide was gently injected intradermally so as to spread diffusely. A volume of 0.01- to 0.02-mL diluted hyaluronic acid was sequentially injected until the skin rose slightly. Overlapping injections were performed at 3 to 5 mm intervals. This process was repeated until the wrinkles were smoothened. This study included 36 cases of facial wrinkles in 34 patients. The follow-up period was 3 to 11 months. Temporary adverse effects were injection-site pain, mild edema, and redness. Most cases showed obvious improvement in skin thickness, elasticity, and smoothening. Complications included irregularities and hyperpigmentation in 3 cases, and 91% were highly satisfied with the antiwrinkle treatment. This method was a safe, economical, and clinically effective antiwrinkle treatment.

  17. [Management of complications after aesthetic hyaluronic acid injections].

    PubMed

    Jahn, K; Homey, B; Gerber, P A

    2014-10-01

    The use of hyaluronic acid fillers for treatment of rhytides (wrinkles) is widespread in aesthetic dermatology and is considered a safe procedure; however, complications can occur especially if the injections are carried out by an inexperienced person and/or with a lack of anatomical knowledge. The two cases presented here exemplify this problem. In conclusion, both cases demonstrate complications after uncritical injection of hyaluronic acid fillers into "risk" or "expert" regions. While the patients in these two cases recovered completely, the injection of filler substances can also lead to the risk of potentially permanent side effects, such as granuloma, necrosis with scar tissue formation and even blindness. The frequency and severity of complications often show a direct correlation with the qualification or expertise of the person treating and hence injection treatments should be performed solely by physicians.

  18. 1- and 2-particle Microrheology of Hyaluronic Acid

    NASA Astrophysics Data System (ADS)

    Sagan, Austin; Kearns, Sarah; Ross, David; Das, Moumita; Thurston, George; Franklin, Scott

    2015-03-01

    Hyaluronic acid (also called HA or Hyaluronan) is a high molecular weight polysaccaride ubiquitous in the extracellular matrix of soft tissue such as cartilage, skin, the eye's vitreous gel and synovial fluid. It has been shown to play an important role in mechanotransduction, cell migration and proliferation, and in tissue morphodynamics. We present a confocal microrheology study of hyaluronic acid of varying concentrations. The mean squared displacement (MSD) of sub-micron colloidal tracer particles is tracked in two dimensions and shows a transition from diffusive motion at low concentrations to small-time trapping by the protein network as the concentration increases. Correlations between particle motion can be used to determine an effective mean-squared displacement which deviates from the single-particle MSD as the fluid becomes less homogeneous. The real and effective mean-squared displacements are used to probe the local and space-averaged frequency dependent rheological properties of the fluid as the concentration changes.

  19. Oil-free hyaluronic acid matrix for serial femtosecond crystallography

    PubMed Central

    Sugahara, Michihiro; Song, Changyong; Suzuki, Mamoru; Masuda, Tetsuya; Inoue, Shigeyuki; Nakane, Takanori; Yumoto, Fumiaki; Nango, Eriko; Tanaka, Rie; Tono, Kensuke; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Yabashi, Makina; Nureki, Osamu; Numata, Keiji; Iwata, So

    2016-01-01

    The grease matrix was originally introduced as a microcrystal-carrier for serial femtosecond crystallography and has been expanded to applications for various types of proteins, including membrane proteins. However, the grease-based matrix has limited application for oil-sensitive proteins. Here we introduce a grease-free, water-based hyaluronic acid matrix. Applications for proteinase K and lysozyme proteins were able to produce electron density maps at 2.3-Å resolution. PMID:27087008

  20. Oil-free hyaluronic acid matrix for serial femtosecond crystallography

    NASA Astrophysics Data System (ADS)

    Sugahara, Michihiro; Song, Changyong; Suzuki, Mamoru; Masuda, Tetsuya; Inoue, Shigeyuki; Nakane, Takanori; Yumoto, Fumiaki; Nango, Eriko; Tanaka, Rie; Tono, Kensuke; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Yabashi, Makina; Nureki, Osamu; Numata, Keiji; Iwata, So

    2016-04-01

    The grease matrix was originally introduced as a microcrystal-carrier for serial femtosecond crystallography and has been expanded to applications for various types of proteins, including membrane proteins. However, the grease-based matrix has limited application for oil-sensitive proteins. Here we introduce a grease-free, water-based hyaluronic acid matrix. Applications for proteinase K and lysozyme proteins were able to produce electron density maps at 2.3-Å resolution.

  1. Managing knee ostheoarthritis: efficacy of hyaluronic acid injections.

    PubMed

    Roque, V; Agre, M; Barroso, J; Brito, I

    2013-01-01

    Osteoarthritis (OA) is the most common form of chronic arthritis worldwide. The etiology of pain in osteoarthritis is multifactoral, and includes mechanical and inflammatory processes. The use of intra-articular viscosupplementation in the nonoperative management of patients with osteoarthritis has become quite popular. Recent clinical data have demonstrated that the anti-inflammatory and chondroprotective actions of hyaluronic acid viscosupplementation reduce pain, from 4 to 14 weeks after injection, while improving patient function. Viscosupplements are comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events, and hyaluronic acid has more prolonged effects than IA corticosteroids. Although several randomized controlled trials have established the efficacy of this treatment modality, additional high quality randomized control studies with appropriate comparison are still required to clearly define the role of intra-articular hyaluronic acid injections in the treatment of osteoarthritis. We review the basic science and development of viscosupplementation and discuss the mounting evidence in support of its efficacy and safety profile.

  2. Photocrosslinked hyaluronic acid hydrogels: natural, biodegradable tissue engineering scaffolds.

    PubMed

    Baier Leach, Jennie; Bivens, Kathryn A; Patrick, Charles W; Schmidt, Christine E

    2003-06-05

    Ideally, rationally designed tissue engineering scaffolds promote natural wound healing and regeneration. Therefore, we sought to synthesize a biomimetic hydrogel specifically designed to promote tissue repair and chose hyaluronic acid (HA; also called hyaluronan) as our initial material. Hyaluronic acid is a naturally occurring polymer associated with various cellular processes involved in wound healing, such as angiogenesis. Hyaluronic acid also presents unique advantages: it is easy to produce and modify, hydrophilic and nonadhesive, and naturally biodegradable. We prepared a range of glycidyl methacrylate-HA (GMHA) conjugates, which were subsequently photopolymerized to form crosslinked GMHA hydrogels. A range of hydrogel degradation rates was achieved as well as a corresponding, modest range of material properties (e.g., swelling, mesh size). Increased amounts of conjugated methacrylate groups corresponded with increased crosslink densities and decreased degradation rates and yet had an insignificant effect on human aortic endothelial cell cytocompatibility and proliferation. Rat subcutaneous implants of the GMHA hydrogels showed good biocompatibility, little inflammatory response, and similar levels of vascularization at the implant edge compared with those of fibrin positive controls. Therefore, these novel GMHA hydrogels are suitable for modification with adhesive peptide sequences (e.g., RGD) and use in a variety of wound-healing applications.

  3. Hyaluronic acid solution injection for upper and lower gastrointestinal bleeding after failed conventional endoscopic therapy.

    PubMed

    Lee, Jin Wook; Kim, Hyung Hun

    2014-03-01

    Hyaluronic acid solution injection can be an additional endoscopic modality for controlling bleeding in difficult cases when other techniques have failed. We evaluated 12 cases in which we used hyaluronic acid solution injection for stopping bleeding. Immediately following hyaluronic acid solution injection, bleeding was controlled in 11 out of 12 cases. There was no clinical evidence of renewed bleeding in 11 cases during follow up.Hyaluronic acid solution injection can be a simple and efficient additional method for controlling upper and lower gastrointestinal bleeding after failed endoscopic therapy.

  4. Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice.

    PubMed

    Schizas, Nikos; Rojas, Ramiro; Kootala, Sujit; Andersson, Brittmarie; Pettersson, Jennie; Hilborn, Jons; Hailer, Nils P

    2014-02-01

    Numerous biomaterials based on extracellular matrix-components have been developed. It was our aim to investigate whether a hyaluronic acid-based hydrogel improves neuronal survival and tissue preservation in organotypic spinal cord slice cultures. Organotypic spinal cord slice cultures were cultured for 4 days in vitro (div), either on hyaluronic acid-based hydrogel (hyaluronic acid-gel group), collagen gel (collagen group), directly on polyethylene terephthalate membrane inserts (control group), or in the presence of soluble hyaluronic acid (soluble hyaluronic acid group). Cultures were immunohistochemically stained against neuronal antigen NeuN and analyzed by confocal laser scanning microscopy. Histochemistry for choline acetyltransferance, glial fibrillary acidic protein, and Griffonia simplicifolia isolectin B4 followed by quantitative analysis was performed to assess motorneurons and different glial populations. Confocal microscopic analysis showed a 4-fold increase in the number of NeuN-positive neurons in the hyaluronic acid-gel group compared to both collagen (p < 0.001) and control groups (p < 0.001). Compared to controls, organotypic spinal cord slice cultures maintained on hyaluronic acid-based hydrogel showed 5.9-fold increased survival of choline acetyltransferance-positive motorneurons (p = 0.008), 2-fold more numerous resting microglial cells in the white matter (p = 0.031), and a 61.4% reduction in the number of activated microglial cells within the grey matter (p = 0.05). Hyaluronic acid-based hydrogel had a shear modulus (G') of ≈1200 Pascals (Pa), which was considerably higher than the ≈25 Pa measured for collagen gel. Soluble hyaluronic acid failed to improve tissue preservation. In conclusion, hyaluronic acid-based hydrogel improves neuronal and - most notably - motorneuron survival in organotypic spinal cord slice cultures and microglial activation is limited. The positive effects of hyaluronic acid-based hydrogel

  5. Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model

    SciTech Connect

    Urman, B.; Gomel, V.; Jetha, N. )

    1991-09-01

    The aim of this study was to determine the effectiveness of hyaluronic acid solution in preventing intraperitoneal (IP) adhesions. The study design was prospective, randomized and blinded and involved 83 rats. Measured serosal injury was inflicted using a CO2 laser on the right uterine horn of the rat. Animals randomized to groups 1 and 2 received either 0.4% hyaluronic acid or its diluent phosphate-buffered saline (PBS) intraperitoneally before and after the injury. In groups 3 and 4, the same solutions were used only after the injury. Postoperative adhesions were assessed at second-look laparotomy. Histologic assessment of the fresh laser injury was carried out on uteri pretreated with hyaluronic acid, PBS, or nothing. Pretreatment with hyaluronic acid was associated with a significant reduction in postoperative adhesions and a significantly decreased crater depth. Hyaluronic acid appears to reduce postoperative IP adhesion formation by coating the serosal surfaces and decreasing the extent of initial tissue injury.

  6. Photo-crosslinked hyaluronic acid coated upconverting nanoparticles

    NASA Astrophysics Data System (ADS)

    Mrazek, Jiri; Kettou, Sofiane; Matuska, Vit; Svozil, Vit; Huerta-Angeles, Gloria; Pospisilova, Martina; Nesporova, Kristina; Velebny, Vladimir

    2017-02-01

    Hyaluronic acid (HA)-coated inorganic nanoparticles display enhanced interaction with the CD44 receptors which are overexpressed in many types of cancer cells. Here, we describe a modification of core-shell β-NaY0.80Yb0.18Er0.02F4@NaYF4 nanoparticles (UCNP) by HA derivative bearing photo-reactive groups. UCNP capped with oleic acid were firstly transferred to aqueous phase by an improved protocol using hydrochloric acid or lactic acid treatment. Subsequently, HA bearing furanacryloyl moieties (HA-FU) was adsorbed on the nanoparticle surface and crosslinked by UV irradiation. The crosslinking resulted in stable HA coating, and no polymer desorption was observed. As-prepared UCNP@HA-FU show a hydrodynamic diameter of about 180 nm and are colloidally stable in water and cell culture media. The cellular uptake by normal human fibroblasts and MDA MB-231 cancer cell line was investigated by upconversion luminescence imaging.

  7. Bio-functionalisation of polydimethylsiloxane with hyaluronic acid and hyaluronic acid--collagen conjugate for neural interfacing.

    PubMed

    Yue, Zhilian; Liu, Xiao; Molino, Paul J; Wallace, Gordon G

    2011-07-01

    In this work, polydimethylsiloxane was activated with oxygen plasma and treated with silanes bearing ethylene imine units. Hyaluronic acid was then grafted covalently onto the aminated surfaces. The influence of silane structure on surface amination was assessed and the influence of the modification on surface physiochemical properties and protein adsorption of modified polydimethylsiloxane were investigated. Collagen type I was conjugated onto the modified polydimethylsiloxane to improve its cyto-compatibility for neural applications. In vitro cultivation of rat pheochromocytoma cells on the bioactive polydimethylsiloxane showed a significant increase in cell growth and differentiation. The potential applications of the bio-functionalized polydimethylsiloxane in cochlear implant electrode arrays were discussed.

  8. Photodegradation of hyaluronic acid: EPR and size exclusion chromatography study.

    PubMed

    Lapcík, L; Chabrecek, P; Stasko, A

    1991-10-15

    Photochemically induced radical reactions involving the lateral sequences and the end macromolecular chain groups of hyaluronic acid in aqueous solutions at 293K were studied by EPR spin trapping technique with DMPO (5,5-dimethylpyrroline-1-oxide). In the first 1-10 minutes of irradiation EPR indicates spin adducts of two carbon centered radicals with the splitting constants of aN = 1.60 mT, aH = 2.51 mT and aN = 1.56 mT, aH = 2.28 mT. After longer irradiation time (over 10 minutes) dominate two further DMPO adducts of radicals centered on hetero-atoms with splitting constants of aN = 1.44 mT, aH = 1.60 mT and of aN = 1.49 mT, aH = 1.49 mT. Simultaneously, molecular weight followed by SEC decreases, suggesting that UV irradiation leads to the breaking of interglycosidic bonds of hyaluronic acid main macromolecular chain.

  9. Hyaluronic Acid Fat Graft Myringoplasty Versus Autologous Platelet Rich Plasma

    PubMed Central

    Alhabib, Salman F.; Saliba, Issam

    2017-01-01

    Background Hyaluronic acid fat graft myringoplasty (HAFGM) is an office-based technique for tympanic membrane perforation (TMP) treatment. It is simple, inexpensive, and performed under local anesthesia at the outpatient office department. We aimed to compare HAFGM technique to a recently described topical use of autologous platelet rich plasma myringoplasty (PRPM) in the repair of TMP. We also aimed to assess the hearing level improvement postoperatively. Methods We conducted a prospective study in an adult tertiary care center between January 2015 and January 2016. Adult patients presenting with simple TMP were operated randomly using either HAFGM or PRPM under local anesthesia in an office-based setting. Perforations were classified into four grades. Success was considered when complete closure is achieved. Audiometric parameters were evaluated pre- and postoperatively. Results We included 27 patients, of whom 16 were operated with HAFGM and 11 were operated with PRPM. Complete closure was achieved in 81.2% and 18.1%, respectively. Postoperatively, no worsening of bone conduction threshold was noted. The study was abandoned due to the low success rate in patients with PRPM. The pure tone audiometry was improved postoperatively in patients with closed tympanic membrane. Conclusions The study was aborted because of the unsatisfactory obtained results using PRPM. It confirms once again the beneficial effect of hyaluronic acid in the healing process when added to fat graft myringoplasty. Furthermore, it requires no hospitalization. PMID:27924172

  10. Biocompatibility of a Self-Assembled Crosslinkable Hyaluronic Acid Nanogel.

    PubMed

    Pedrosa, Sílvia Santos; Pereira, Paula; Correia, Alexandra; Moreira, Susana; Rocha, Hugo; Gama, Francisco Miguel

    2016-11-01

    Hyaluronic acid nanogel (HyA-AT) is a redox sensitive crosslinkable nanogel, obtained through the conjugation of a thiolated hydrophobic molecule to the hyaluronic acid chain. Engineered nanogel was studied for its biocompatibility, including immunocompatibility and hemocompatability. The nanogel did not compromise the metabolic activity or cellular membrane integrity of 3T3, microvascular endothelial cells, and RAW 264.7 cell lines, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase release assays. Also, we didn't observe any apoptotic effect on these cell lines through the Annexin V-FITC test. Furthermore, the nanogel cell internalization was analyzed using murine bone marrow derived macrophages, and the in vivo and ex vivo biodistribution of the Cy5.5 labeled nanogel was monitored using a non-invasive near-infrared fluorescence imaging system. The HyA-AT nanogel exhibits fairly a long half-live in the blood stream, thus showing potential for drug delivery applications.

  11. Hyaluronic Acid Gel Injection to Prevent Thermal Injury of Adjacent Gastrointestinal Tract during Percutaneous Liver Radiofrequency Ablation

    SciTech Connect

    Hasegawa, Takaaki Takaki, Haruyuki; Miyagi, Hideki; Nakatsuka, Atsuhiro; Uraki, Junji; Yamanaka, Takashi; Fujimori, Masashi; Sakuma, Hajime; Yamakado, Koichiro

    2013-08-01

    This study evaluated the safety, feasibility, and clinical utility of hyaluronic acid gel injection to separate the gastrointestinal tract from the tumor during liver radiofrequency ablation (RFA). Eleven patients with liver tumors measuring 0.9-3.5 cm (mean {+-} standard deviation, 2.1 {+-} 0.8 cm) that were adjacent to the gastrointestinal tracts received RFA after the mixture of hyaluronic acid gel and contrast material (volume, 26.4 {+-} 14.5 mL; range, 10-60 mL) was injected between the tumor and the gastrointestinal tract under computed tomographic-fluoroscopic guidance. Each tumor was separated from the gastrointestinal tract by 1.0-1.5 cm (distance, 1.2 {+-} 0.2 cm) after injection of hyaluronic acid gel, and subsequent RFA was performed without any complications in all patients. Although tumor enhancement disappeared in all patients, local tumor progression was found in a patient (9.1 %, 1 of 11) during the follow-up of 5.5 {+-} 3.2 months (range, 0.4-9.9 months). In conclusion, hyaluronic acid gel injection is a safe and useful technique to avoid thermal injury of the adjacent gastrointestinal tract during liver RFA.

  12. Hyaluronic acid gel injection to prevent thermal injury of adjacent gastrointestinal tract during percutaneous liver radiofrequency ablation.

    PubMed

    Hasegawa, Takaaki; Takaki, Haruyuki; Miyagi, Hideki; Nakatsuka, Atsuhiro; Uraki, Junji; Yamanaka, Takashi; Fujimori, Masashi; Sakuma, Hajime; Yamakado, Koichiro

    2013-08-01

    This study evaluated the safety, feasibility, and clinical utility of hyaluronic acid gel injection to separate the gastrointestinal tract from the tumor during liver radiofrequency ablation (RFA). Eleven patients with liver tumors measuring 0.9-3.5 cm (mean ± standard deviation, 2.1 ± 0.8 cm) that were adjacent to the gastrointestinal tracts received RFA after the mixture of hyaluronic acid gel and contrast material (volume, 26.4 ± 14.5 mL; range, 10-60 mL) was injected between the tumor and the gastrointestinal tract under computed tomographic-fluoroscopic guidance. Each tumor was separated from the gastrointestinal tract by 1.0-1.5 cm (distance, 1.2 ± 0.2 cm) after injection of hyaluronic acid gel, and subsequent RFA was performed without any complications in all patients. Although tumor enhancement disappeared in all patients, local tumor progression was found in a patient (9.1%, 1 of 11) during the follow-up of 5.5 ± 3.2 months (range, 0.4-9.9 months). In conclusion, hyaluronic acid gel injection is a safe and useful technique to avoid thermal injury of the adjacent gastrointestinal tract during liver RFA.

  13. Production and characterization of bacterial cellulose membranes with hyaluronic acid from chicken comb.

    PubMed

    de Oliveira, Sabrina Alves; da Silva, Bruno Campos; Riegel-Vidotti, Izabel Cristina; Urbano, Alexandre; de Sousa Faria-Tischer, Paula Cristina; Tischer, Cesar Augusto

    2017-04-01

    The bacterial cellulose (BC), from Gluconacetobacter hansenii, is a biofilm with a high degree of crystallinity that can be used for therapeutic purposes and as a candidate for healing wounds. Hyaluronic acid (HA) is a constitutive polysaccharide found in the extracellular matrix and is a material used in tissue engineering and scaffolding for tissue regeneration. In this study, polymeric composites were produced in presence of hyaluronic acid isolated from chicken comb on different days of fermentation, specifically on the first (BCHA-SABT0) and third day (BCHA-SABT3) of fermentation. The structural characteristics, thermal stability and molar mass of hyaluronic acid from chicken comb were evaluated. Native membrane and polymeric composites were characterized with respect to their morphology and crystallinity. The optimized process of extraction and purification of hyaluronic acid resulted in low molar mass hyaluronic acid with structural characteristics similar to the standard commercial hyaluronic acid. The results demonstrate that the polymeric composites (BC/HA-SAB) can be produced in situ. The membranes produced on the third day presented better incorporation of HA-SAB between cellulose microfiber, resulting in membranes with higher thermal stability, higher roughness and lower crystallinity. The biocompatiblily of bacterial cellulose and the importance of hyaluronic acid as a component of extracellular matrix qualify the polymeric composites as promising biomaterials for tissue engineering.

  14. Antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections.

    PubMed

    Drago, Lorenzo; Cappelletti, Laura; De Vecchi, Elena; Pignataro, Lorenzo; Torretta, Sara; Mattina, Roberto

    2014-10-01

    To address the problem of limited efficacy of existing antibiotics in the treatment of bacterial biofilm, it is necessary to find alternative remedies. One candidate could be hyaluronic acid; this study therefore aimed to evaluate the in vitro antiadhesive and antibiofilm activity of hyaluronic acid toward bacterial species commonly isolated from respiratory infections. Interference exerted on bacterial adhesion was evaluated by using Hep-2 cells, while the antibiofilm activity was assessed by means of spectrophotometry after incubation of biofilm with hyaluronic acid and staining with crystal violet. Our data suggest that hyaluronic acid is able to interfere with bacterial adhesion to a cellular substrate in a concentration-dependent manner, being notably active when assessed as pure substance. Moreover, we found that Staphylococcus aureus biofilm was more sensitive to the action of hyaluronic acid than biofilm produced by Haemophilus influenzae and Moraxella catarrhalis. In conclusion, hyaluronic acid is characterized by notable antiadhesive properties, while it shows a moderate activity against bacterial biofilm. As bacterial adhesion to oral cells is the first step for colonization, these results further sustain the role of hyaluronic acid in prevention of respiratory infections.

  15. Hyaluronic acid as capacitation inductor: metabolic changes and membrane-associated adenylate cyclase regulation.

    PubMed

    Fernández, S; Córdoba, M

    2014-12-01

    The aim of this research was to study the effect of hyaluronic acid on bovine cryopreserved spermatozoa compared with heparin as regards the variation of capacitation induction, cellular oxidative metabolism and intracellular signal induced by membrane-associated adenylate cyclase to propose hyaluronic acid as a capacitation inductor. Heparin or hyaluronic acid and lysophosphatidylcholine were used to induce sperm capacitation and acrosome reaction, respectively. 2',5'-dideoxyadenosine was used as a membrane-associated adenylate cyclase inhibitor. The highest percentages of capacitated spermatozoa and live spermatozoa with acrosome integrity were obtained by incubating sperm for 60 min using 1000 μg/ml hyaluronic acid. In these conditions, capacitation induced by hyaluronic acid was lower compared with heparin; nonetheless both glycosaminoglycans promote intracellular changes that allow true acrosome reaction in vitro induced by lysophosphatidylcholine in bovine spermatozoa. Oxygen consumption in heparin-capacitated spermatozoa was significantly higher than in hyaluronic acid-treated spermatozoa. With all treatments, mitochondrial coupling was observed when a specific uncoupler of the respiratory chain was added. The inhibition of membrane-associated adenylate cyclase significantly blocked capacitation induction produced by hyaluronic acid, maintaining a basal sperm oxygen uptake in contrast to heparin effect in which both sperm parameters were inhibited, suggesting that the membrane-associated adenylate cyclase activation is involved in the intracellular signal mechanisms induced by both capacitation inductors, but only regulates mitochondrial oxidative phosphorylation in heparin-capacitated spermatozoa.

  16. Microbial production of hyaluronic acid: current state, challenges, and perspectives

    PubMed Central

    2011-01-01

    Hyaluronic acid (HA) is a natural and linear polymer composed of repeating disaccharide units of β-1, 3-N-acetyl glucosamine and β-1, 4-glucuronic acid with a molecular weight up to 6 million Daltons. With excellent viscoelasticity, high moisture retention capacity, and high biocompatibility, HA finds a wide-range of applications in medicine, cosmetics, and nutraceuticals. Traditionally HA was extracted from rooster combs, and now it is mainly produced via streptococcal fermentation. Recently the production of HA via recombinant systems has received increasing interest due to the avoidance of potential toxins. This work summarizes the research history and current commercial market of HA, and then deeply analyzes the current state of microbial production of HA by Streptococcus zooepidemicus and recombinant systems, and finally discusses the challenges facing microbial HA production and proposes several research outlines to meet the challenges. PMID:22088095

  17. Effect of adipic dihydrazide modification on the performance of collagen/hyaluronic acid scaffold.

    PubMed

    Zhang, Ling; Xiao, Yumei; Jiang, Bo; Fan, Hongsong; Zhang, Xingdong

    2010-02-01

    Collagen and hydrazide-functionalized hyaluronic acid derivatives were hybridized by gelating and genipin crosslinking to form composite hydrogel. The study contributed to the understanding of the effects of adipic dihydrazide modification on the physicochemical and biological properties of the collagen/hyaluronic acid scaffold. The investigation included morphology observation, mechanical measurement, swelling evaluation, and collagenase degradation. The results revealed that the stability of composites was increased through adipic dihydrazide modification and genipin crosslinking. The improved biocompatibility and retention of hyaluronic acid made the composite material more favorable to chondrocytes growing, suggesting the prepared scaffold might be high potential for chondrogenesis.

  18. Isolation and characterization of hyaluronic acid from marine organisms.

    PubMed

    Giji, Sadhasivam; Arumugam, Muthuvel

    2014-01-01

    Hyaluronic acid (HA) being a viscous slippery substance is a multifunctional glue with immense therapeutic applications such as ophthalmic surgery, orthopedic surgery and rheumatology, drug delivery systems, pulmonary pathology, joint pathologies, and tissue engineering. Although HA has been isolated from terrestrial origin (human umbilical cord, rooster comb, bacterial sources, etc.) so far, the increasing interest on this polysaccharide significantly aroused the alternative search from marine sources since it is at the preliminary level. Enthrallingly, marine environments are considered more biologically diverse than terrestrial environments. Although numerous methods have been described for the extraction and purification of HA, the hitch on the isolation methods which greatly influences the yield as well as the molecular weight of the polymer still exists. Adaptation of suitable method is essential in this venture. Stimulated by the developed technology, to sketch the steps involved in isolation and analytical techniques for characterization of this polymer, a brief report on the concerned approach has been reviewed.

  19. Hyaluronic acid synthesis is required for zebrafish tail fin regeneration

    PubMed Central

    Ouyang, Xiaohu; Panetta, Nicholas J.; Talbott, Maya D.; Payumo, Alexander Y.; Halluin, Caroline; Longaker, Michael T.

    2017-01-01

    Using genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-ß signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impairs tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation. In addition, 4-MU reduces the expression of genes associated with wound epithelium and blastema function. Treatment with glycogen synthase kinase 3 inhibitors rescues 4-MU-induced defects in cell proliferation and tail regeneration, while restoring a subset of wound epithelium and blastema markers. Our findings demonstrate a role for HA biosynthesis in zebrafish tail regeneration and delineate its epistatic relationships with other regenerative processes. PMID:28207787

  20. [A case of nasal tip necrosis after hyaluronic acid injection].

    PubMed

    Honart, J-F; Duron, J-B; Mazouz Dorval, S; Rausky, J; Revol, M

    2013-12-01

    Hyaluronic acid (HA) is the most used dermal filler. Some complications associated with its use have been described, but most of them are rare and benign. We report an exceptional case of skin necrosis of the tip of the nose, in a 22-year-old patient, after HA injection. The initial appearance may occurred subsequent aesthetic sequels. After necrotic tissue excision, patient was followed in rapid succession. Daily local care has led to wound healing, without any important sequel. This rare complication reminds us that HA injections are not without risk, despite their apparent simplicity of use. Moreover, the case presented confirms the potential healing of the nasal tip, allowing treatment with wound healing, rather than other early invasive procedure.

  1. Protective effect of hyaluronic acid on cryopreserved boar sperm.

    PubMed

    Qian, Li; Yu, Sijiu; Zhou, Yan

    2016-06-01

    This study aimed to evaluate the effects of supplementing freezing and thawing media with hyaluronic acid (HA) on the quality parameters of frozen-thawed boar spermatozoa. Boar semen samples were collected from seven mature Yorkshire boars once a week using the gloved hand technique; these samples were frozen-thawed in the extender with added HA. Boar sperm was cryopreserved in the extender with HA added at concentrations of 0 (used as control), 4, 6, 8, 8 and 12mg/L, and their effects on the quality of frozen-thawed boar sperm were evaluated. HA addition to the extender significantly improved sperm motility, sperm membrane integrity, mitochondrial activity, acrosomal integrity, superoxide dismutase and catalase activity, but decreased sperm malondialdehyde level (p<0.05). Therefore, HA could be a promising cryoprotectant for boar sperm.

  2. Permanent hair dye-incorporated hyaluronic acid nanoparticles.

    PubMed

    Lee, Hye-Young; Jeong, Young-Il; Kim, Da-Hye; Choi, Ki-Choon

    2013-01-01

    We prepared p-phenylenediamine (PDA)-incorporated nanoparticles using hyaluronic acid (HA). PDA-incorporated HA nanoparticles have spherical shapes and sizes were less than 300 nm. The results of FT-IR spectra indicated that PDA-incorporated HA nanoparticles were formed by ion-complex formation between amine group of PDA and carboxyl group of HA. Furthermore, powder-X-ray diffractogram (XRD) measurement showed that intrinsic crystalline peak of PDA disappeared by formation of nanoparticle with HA at XRD measurement. These results indicated that PDA-incorporated HA nanoparticles were formed by ion-complex formation. At drug release study, the higher PDA contents induced faster release rate from nanoparticles. PDA-incorporated nanoparticles showed reduced intrinsic toxicity against HaCaT human keratinocyte cells at MTT assay and apoptosis assay. We suggest that PDA-incorporated HA nanoparticles are promising candidates for novel permanent hair dye.

  3. Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts.

    PubMed

    Maeda-Sano, Katsura; Gotoh, Mari; Morohoshi, Toshiro; Someya, Takao; Murofushi, Hiromu; Murakami-Murofushi, Kimiko

    2014-09-01

    Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway.

  4. [Hyaluronic Acid (hyalgan(r)) in the treatment of gonarthritis.].

    PubMed

    Pavelka, K; Vlasáková, V; Vítová, J; Stehlíková, H; Slanský, J

    1995-01-01

    The authors made an open multicentre clinical study with the administration of hyaluronic acid (Hyalgan(R) - Fidia) in patients with gonarthritis. The study comprised 31 patients with gonarthritis grade II-III according to Kellgren, 30 of whom completed the study. Hyalgan was administered to the patients - vials á 2 ml in five injections in weekly intervals by the intraarticular route. The patients were followed up for another three months after completed treatment. A significant decline of pain on the visual analogue scale (VAS) was recorded already two weeks after onset of treatment (p = 0.001) and this decline persisted for another 13 weeks after termination of treatment. The algofunctional indices (Lequesne, Jezek) also declined after the first injection, whereby a statistically significant reduction was recorded still after 12 weeks, as compared with values before the onset of treatment (p = 0.001). Similar results were obtained also in objective evaluations (effusion, temperature above joint, tenderness). Already after the second injection a significantly shorter time was required for a 20 m walk. The mean daily paracetamol consumption declined from a mean value of 1496 +/- 777 mg before administration to 670 6 661 mg at the end of the investigation (p = 0.00006). Undesirable effects (increased intensity of pain after puncture) was recorded in one patient (3.3%). Evidence was provided that Hyalgan(R) belongs as to its profile of effectiveness among so-called SYSADOAs (symptomatic slow acting drugs for OA). Treatment is quite safe. Key words: knee osteoarthritis, hyaluronic acid, i. a. treatment.

  5. Sedimentation properties in density gradients correspond with levels of sperm DNA fragmentation, chromatin compaction and binding affinity to hyaluronic acid.

    PubMed

    Torabi, Forough; Binduraihem, Adel; Miller, David

    2017-03-01

    Mature spermatozoa bind hyaluronic acid in the extracellular matrix via hyaladherins. Immature spermatozoa may be unable to interact because they do not express the appropriate hyaladherins on their surface. Fresh human semen samples were fractionated using differential density gradient centrifugation (DDGC) and the ability of these fractions to bind hyaluronic acid was evaluated. The presence of sperm hyaladherins was also assessed. CD44 was located mainly on the acrosome and equatorial segment and became more restricted to the equatorial segment in capacitated spermatozoa. Hyaluronic acid-TRITC (hyaluronic acid conjugated with tetramethylrhodamine isothiocyanante), a generic hyaluronic-acid-binding reagent, labelled the membrane and the neck region, particularly after capacitation. Sperm populations obtained after DDGC or after interaction with hyaluronic acid were assessed for DNA fragmentation and chromatin maturity. Strong relationships between both measures and sperm sedimentation and hyaluronic-acid-binding profiles were revealed. Capacitation enhanced hyaluronic acid binding of both DDGC-pelleted sperm and sperm washed free of seminal fluid. In conclusion, hyaladherins were detected on human sperm and a higher capacity for sperm hyaluronic-acid-binding was shown to correspond with their DDGC sedimentation profiles and with lower levels of DNA fragmentation and better chromatin maturity. Capacitation induced changes in the distribution and presence of hyaladherins may enhance hyaluronic-acid-binding.

  6. Cashew apple juice as microbial cultivation medium for non-immunogenic hyaluronic acid production

    PubMed Central

    Oliveira, Adriano H.; Ogrodowski, Cristiane C.; de Macedo, André C.; Santana, Maria Helena A.; Gonçalves, Luciana R.B.

    2013-01-01

    In this work, natural cashew apple juice was used as cultivation medium as an alternative to substitute brain heart infusion medium. The effect of aeration and juice supplementation with yeast extract on the production of hyaluronic acid in batch fermentation was also investigated. Similar levels of cell mass were obtained in inoculum using cashew apple juice supplemented with yeast extract or the conventional brain heart infusion medium. Fermentation in Erlenmeyer flasks produced low biomass and hyaluronic acid concentrations. The hyaluronic acid concentration and viscosity increased from 0.15 g/L and 3.87 cP (no aeration or medium supplementation) to 1.76 g/L and 107 cP, when aeration (2 vvm) and 60 g/L of yeast extract were used. The results suggest the production of low-molecular weight hyaluronic acid oligomers instead of the high molecular weight polymer. PMID:24688498

  7. [Preparation of galactosylated hyaluronic acid/chitosan scaffold for liver tissue engineering].

    PubMed

    Fan, Jinyong; Shang, Yi; Yang, Jun; Yuan, Yingjin

    2009-12-01

    The purpose of this research is to construct a kind of 3D-Scaffold with galactose-carrying polysaccharide for improving the function of hepatocytes in vitro. Galactose moieties were covalently coupled with hyaluronic acid through ethylenediamine. Galactosylated hyaluronic acid/chitosan scaffolds were prepared by lyophilization. The characteristics of the scaffolds such as morphology, hydrophilicity, and mechanical properties were investigated. The results indicated that the porosity and the pore size of the scaffolds made in -20 degrees C were useful used for culturing hepatocytes. And, the incorporating of hyaluronic acid in chitosan network improved the hydrophilicity and mechanical properties of the scaffolds. Rat primary hepatocytes growing in the scaffolds observed by phase-contrast microscope showed the multicellular spheroid morphologies. Therefore, galactosylated hyaluronic acid/chitosan scaffolds could be used as a promising scaffold for liver tissue engineering.

  8. The influence of polymeric component of bioactive glass-based nanocomposite paste on its rheological behaviors and in vitro responses: hyaluronic acid versus sodium alginate.

    PubMed

    Sohrabi, Mehri; Hesaraki, Saeed; Kazemzadeh, Asghar

    2014-04-01

    Different biocomposite pastes were prepared from a solid phase that was nanoparticles of sol-gel-derived bioactive glass and different liquid phases including 3% hyaluronic acid solution, sodium alginate solutions (3% and 10 %) or mixtures of hyaluronic acid and sodium alginate (3% or 10 %) solutions in 50:50 volume ratio. Rheological properties of the pastes were measured in both rotatory and oscillatory modes. The washout behavior and in vitro apatite formation of the pastes were determined by soaking them in simulated body fluid under dynamic situation for 14 days. The proliferation and alkaline phosphatase activity of MG-63 osteoblastic cells were also determined using extracts of the pastes. All pastes could be easily injected from the standard syringes with different tip diameters. All pastes exhibited visco-elastic character, but a nonthixotropic paste was obtained using hyaluronic acid in which the loss modulus was higher than the storage modulus. The thixotropy and storage modulus were increasingly improved by adding/using sodium alginate as mixing liquid. Moreover, the pastes in which the liquid phase was sodium alginate or mixture of hyaluronic acid and 10% sodium alginate solution revealed better apatite formation ability and washout resistance than that made of hyaluronic acid alone. No cytotoxicity effects were observed by extracts of the pastes on osteoblasts but better alkaline phosphatase activity was found for the pastes containing hyaluronic acid. Overall, injectable biocomposites can be produced by mixing bioactive glass nanoparticles and sodium alginate/hyaluronic acid polymers. They are potentially useful for hard and even soft tissues treatments.

  9. Platelet-derived Factor Concentrates with Hyaluronic Acid Scaffolds for Treatment of Deep Burn Wounds

    PubMed Central

    Minabe, Toshiharu; Yamakawa, Tomomi; Araki, Jun; Sano, Hitomi; Yoshimura, Kotaro

    2016-01-01

    Summary: A deep burn wound is a critical condition that generally necessitates vascularized tissue coverage. We performed the injection of platelet-derived factor concentrates combined with non–cross-linked hyaluronic acid scaffolds for 2 patients with critical burn wounds with bone and tendon exposure and achieved successful healing. Hyaluronic acid was considered to have served as a controlled-release carrier of platelet-derived factors, being clinically effective for the treatment of deep burn wounds. PMID:27826482

  10. Constructing a recombinant hyaluronic acid biosynthesis operon and producing food-grade hyaluronic acid in Lactococcus lactis.

    PubMed

    Sheng, Juzheng; Ling, Peixue; Wang, Fengshan

    2015-02-01

    Hyaluronic acid (HA), a natural high molecular weight polysaccharide, is produced by Streptococcus zooepidemicus. However, Streptococcus has several drawbacks including its potential to produce exotoxins, so there is demand for an alternative HA source. Here, a recombinant HA biosynthesis operon, as well as the HA biosynthesis operon of S. zooepidemicus were introduced into L. lactis using the nisin-controlled expression system, respectively. HA was successfully synthesized by recombinant L. lactis. Furthermore, overexpression of the endogenous enzymes directing the synthesis of precursor sugars was effective at increasing HA production, and increasing the supply of UDP-activated monosaccharide donors aided synthesis of monodisperse HA polysaccharides. Besides GRAS host strain (L. lactis) and NICE system, the selecting marker (lacF gene) of the recombinant strain is also food grade. Therefore, HA produced by recombinant L. lactis overcomes the problems associated with Streptococcus and provides a source of food-grading HA appropriate for widespread biotechnological applications.

  11. An In Vivo Study of Composite Microgels Based on Hyaluronic Acid and Gelatin for the Reconstruction of Surgically Injured Rat Vocal Folds

    ERIC Educational Resources Information Center

    Coppoolse, Jiska M. S.; Van Kooten, T. G.; Heris, Hossein K.; Mongeau, Luc; Li, Nicole Y. K.; Thibeault, Susan L.; Pitaro, Jacob; Akinpelu, Olubunm; Daniel, Sam J.

    2014-01-01

    Purpose: The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid-gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. Method: Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 µl saline (placebo controls),…

  12. The penetration of topically applied ointment containing hyaluronic acid in rabbit tissues.

    PubMed

    Birkenfeld, B; Parafiniuk, M; Bielecka-Grzela, S; Klimowicz, A; Piwowarska-Bilska, H; Mikołajczak, R; Listewnik, M H; Kurzejamska-Parafiniuk, M; Osowski, A; Byszewska-Szpocińska, E

    2011-01-01

    The properties of hyaluronic acid used for treatment of acute and chronic joint disease are known for many years and this compound is widely used both in humans and animals. To obtain a therapeutic effect of a certain drug, the appropriate concentration in the target organ or tissue is important. The application of labeled compounds is one of the frequently applied techniques to estimate drug penetration into the skin and other body tissues or organs. The aim of the study was to evaluate the penetration of hyaluronic acid labeled with I-131 through the skin and its distribution within the knee joint and other internal organs in rabbits after a topical application of an ointment containing hyaluronic acid. The experiment was performed on 22 albino rabbits divided into control and examined groups. Fifteen rabbits were exposed to the multicomponent ointment containing hyaluronic acid labeled with I-131. Time of exposure was 48 hours. Hyaluronate penetrated to a high degree into the examined tissues. No significant differences in terms of leg tissue activity were observed between a leg tissue exposed to labeled ointment and that unexposed, suggesting that after topical administration, the active component of the ointment is delivered to the joint via the blood stream. Hyaluronate applied topically penetrates through the skin into the rabbit tissues and organs and into the joint fluid of both legs (exposed and not exposed). This route of administration seems to be useful for this drug delivery and allows to avoid unnecessary side effects.

  13. Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit.

    PubMed Central

    Fraser, J R; Laurent, T C; Pertoft, H; Baxter, E

    1981-01-01

    The plasma clearance, tissue distribution and metabolism of hyaluronic acid were studied with a high average molecular weight [3H]acetyl-labelled hyaluronic acid synthesized in synovial cell cultures. After intravenous injection in the rabbit the label disappeared from the plasma with a half-life of 2.5--4.5 min, which corresponds to a normal hyaluronic acid clearance of approx. 10 mg/day per kg body weight. Injection of unlabelled hyaluronic acid 15 min after the tracer failed to reverse its absorption. Clearance of labelled polymer was retarded by prior injection of excess unlabelled hyaluronic acid. The maximum clearance capacity was estimated in these circumstances to be about 30 mg/day per kg body wt. The injected material was concentrated in the liver and spleen. As much as 88% of the label was absorbed by the liver, where it was found almost entirely in non-parenchymal cells. Degradation was rapid and complete, since volatile material, presumably 3H2O, appeared in the plasma within 20 min. Undegraded [3H]hyaluronic acid, small labelled residues and 3H2O were detected in the liver, but there was little evidence of intermediate oligosaccharides. No metabolite except 3H2O was recognized in plasma or urine. Two-thirds of the radioactivity was retained in the body water 24 h later, and small amounts were found in liver lipids. Radioactivity did not decline in the spleen as rapidly as in the liver. The upper molecular weight limit for renal excretion was about 25 000. Renal excretion played a negligible part in clearance. It is concluded that hyaluronic acid is removed from the plasma and degraded quickly by an efficient extrarenal system with a high reserve capacity, sited mainly in the liver. PMID:7340841

  14. Comparison of the effects of hyaluronidase and hyaluronic acid on probiotics growth

    PubMed Central

    2013-01-01

    Background Hyaluronic acid has several clinical applications. Recent evidences suggested antimicrobial properties against several pathogens. The aim of the present survey was to evaluate the effect of hyaluronic acid, alone or in combination with hyaluronidase, on protechnological or probiotic strains. Results The role of hyaluronic acid and hyaluronidase on in vitro growth rate of different lactic acid bacteria was investigated. Standard methods revealed that low concentrations of hyaluronic acid (0.5-0.125 mg ml-1), and hyaluronidase at fixed concentration (1.6 mg ml-1), resulted in an increased bacterial strains growth up to 72 hours whereas higher concentrations of the acid (2 and 1 mg ml-1), and hyaluronidase at the same fixed concentration, reduced the bacterial growth. Conclusions Observations might suggest a possible protective role of both hyaluronidase and low doses of hyaluronic acid towards some strains, supporting their in vivo proliferation and engraftment after oral administration. Hyaluronidase introduction into growth medium greatly enhanced the bacterial growth up to 72 hours. PMID:24188369

  15. Hypocrellin B and paclitaxel-encapsulated hyaluronic acid-ceramide nanoparticles for targeted photodynamic therapy in lung cancer.

    PubMed

    Chang, Ji-Eun; Cho, Hyun-Jong; Yi, Eunjue; Kim, Dae-Duk; Jheon, Sanghoon

    2016-05-01

    To increase the therapeutic efficacy of photodynamic therapy (PDT) in treating lung cancer, we developed both photosensitizer and anticancer drug encapsulated hyaluronic acid-ceramide nanoparticles. Based on our previous study, a co-delivery system of photosensitizers and anticancer agents greatly improves the therapeutic effect of PDT. Furthermore, hyaluronic acid-ceramide-based nanoparticles are ideal targeting carriers for lung cancer. In vitro phototoxicity in A549 (human lung adenocarcinoma) cells and in vivo antitumor efficacy in A549 tumor-bearing mice treated with hypocrellin B (HB)-loaded nanoparticles (HB-NPs) or hypocrellin B and paclitaxel loaded nanoparticles (HB-P-NPs) were evaluated. Cell viability assay, microscopic analysis and FACS analysis were performed for the in vitro studies and HB-P-NPs showed enhanced phototoxicity compared with HB-NPs. In the animal study, the tumor volume change and the histological analysis was studied and the anticancer efficacy improved in the order of free HBhyaluronic acid-ceramide nanoparticle-based targeted delivery improved the effects of PDT in lung cancer in mice.

  16. Synthesis and Characterization of Hybrid Hyaluronic Acid-Gelatin Hydrogels

    PubMed Central

    Camci-Unal, Gulden; Cuttica, Davide; Annabi, Nasim; Demarchi, Danilo; Khademhosseini, Ali

    2013-01-01

    Biomimetic hybrid hydrogels have generated broad interest in tissue engineering and regenerative medicine. Hyaluronic acid (HA) and gelatin (hydrolyzed collagen) are naturally derived polymers and biodegradable under physiological conditions. Moreover, collagen and HA are major components of the extracellular matrix (ECM) in most of the tissues (e.g. cardiovascular, cartilage, neural). When used as a hybrid material, HA-gelatin hydrogels may enable mimicking the ECM of native tissues. Although HA-gelatin hybrid hydrogels are promising biomimetic substrates, their material properties have not been thoroughly characterized in the literature. Herein, we generated hybrid hydrogels with tunable physical and biological properties by using different concentrations of HA and gelatin. The physical properties of the fabricated hydrogels including swelling ratio, degradation, and mechanical properties were investigated. In addition, in vitro cellular responses in both two and three dimensional (2D and 3D) culture conditions were assessed. It was found that the addition of gelatin methacrylate (GelMA) into HA methacrylate (HAMA) promoted cell spreading in the hybrid hydogels. Moreover, the hybrid hydrogels showed significantly improved mechanical properties compared to their single component analogs. The HAMA-GelMA hydrogels exhibited remarkable tunability behavior and may be useful for cardiovascular tissue engineering applications. PMID:23419055

  17. Hyaluronic Acid Based Hydrogels for Regenerative Medicine Applications

    PubMed Central

    Borzacchiello, Assunta; Russo, Luisa; Malle, Birgitte M.; Schwach-Abdellaoui, Khadija; Ambrosio, Luigi

    2015-01-01

    Hyaluronic acid (HA) hydrogels, obtained by cross-linking HA molecules with divinyl sulfone (DVS) based on a simple, reproducible, and safe process that does not employ any organic solvents, were developed. Owing to an innovative preparation method the resulting homogeneous hydrogels do not contain any detectable residual cross-linking agent and are easier to inject through a fine needle. HA hydrogels were characterized in terms of degradation and biological properties, viscoelasticity, injectability, and network structural parameters. They exhibit a rheological behaviour typical of strong gels and show improved viscoelastic properties by increasing HA concentration and decreasing HA/DVS weight ratio. Furthermore, it was demonstrated that processes such as sterilization and extrusion through clinical needles do not imply significant alteration of viscoelastic properties. Both SANS and rheological tests indicated that the cross-links appear to compact the network, resulting in a reduction of the mesh size by increasing the cross-linker amount. In vitro degradation tests of the HA hydrogels demonstrated that these new hydrogels show a good stability against enzymatic degradation, which increases by increasing HA concentration and decreasing HA/DVS weight ratio. Finally, the hydrogels show a good biocompatibility confirmed by in vitro tests. PMID:26090451

  18. Hyaluronic acid ion-pairing nanoparticles for targeted tumor therapy.

    PubMed

    Li, Wenhao; Yi, Xiaoli; Liu, Xing; Zhang, Zhirong; Fu, Yao; Gong, Tao

    2016-03-10

    Hyaluronic acid (HA)-based doxorubicin (DOX) nanoparticles (HA-NPs) were fabricated via ion-pairing between positively charged DOX and negatively charged HA, which displayed near-spherical shapes with an average size distribution of 180.2nm (PDI=0.184). Next, HA-NPs were encapsulated in liposomal carriers to afford HA-based DOX liposomes (HA-LPs), which also showed near-spherical morphology with an average size of 130.5nm (PDI=0.201). HA-NPs and HA-LPs displayed desirable sustained-release profiles compared to free DOX, and moreover, HA-LPs were proven to prevent premature release of DOX from HA-NPs. Cell based studies demonstrated HA-NPs and HA-LPs were selectively taken up by CD44(+) tumor cells, and DOX was released intracellularly to target the cell nuclei. Both HA-NPs and HA-LPs showed comparable levels of penetration efficiency in tumor spheroids. In vivo studies revealed that HA-NPs and HA-LPs significantly prolonged the blood circulation time of DOX, decreased accumulation in the normal tissues and enriched drugs into the tumors. Furthermore, HA-NPs and HA-LPs greatly enhanced therapeutic efficacy of DOX in tumor-bearing mice and minimized systemic toxicity against vital organs. In sum, HA-NPs and HA-LPs represent promising nanocarriers for CD44(+) tumor-targeted delivery.

  19. Paclitaxel isomerisation in polymeric micelles based on hydrophobized hyaluronic acid.

    PubMed

    Smejkalová, Daniela; Nešporová, Kristina; Hermannová, Martina; Huerta-Angeles, Gloria; Cožíková, Dagmar; Vištejnová, Lucie; Safránková, Barbora; Novotný, Jaroslav; Kučerík, Jiří; Velebný, Vladimír

    2014-05-15

    Physical and chemical structure of paclitaxel (PTX) was studied after its incorporation into polymeric micelles made of hyaluronic acid (HA) (Mw=15 kDa) grafted with C6 or C18:1 acyl chains. PTX was physically incorporated into the micellar core by solvent evaporation technique. Maximum loading capacity for HAC6 and HAC18:1 was determined to be 2 and 14 wt.%, respectively. The loading efficiency was higher for HAC18:1 and reached 70%. Independently of the derivative, loaded HA micelles had spherical size of approximately 60-80 nm and demonstrated slow and sustained release of PTX in vitro. PTX largely changed its form from crystalline to amorphous after its incorporation into the micelle's interior. This transformation increased PTX sensitivity towards stressing conditions, mainly to UV light exposure, during which the structure of amorphous PTX isomerized and formed C3C11 bond within its structure. In vitro cytotoxicity assay revealed that polymeric micelles loaded with PTX isomer had higher cytotoxic effect to normal human dermal fibroblasts (NHDF) and human colon carcinoma cells (HCT-116) than the same micelles loaded with non-isomerized PTX. Further observation indicated that PTX isomer influenced in different ways cell morphology and markers of cell cycle. Taken together, PTX isomer loaded in nanocarrier systems may have improved anticancer activity in vivo than pure PTX.

  20. Carbon nanotubes induced gelation of unmodified hyaluronic acid.

    PubMed

    Zamora-Ledezma, Camilo; Buisson, Lionel; Moulton, Simon E; Wallace, Gordon; Zakri, Cécile; Blanc, Christophe; Anglaret, Eric; Poulin, Philippe

    2013-08-13

    This work reports an experimental study of the kinetics and mechanisms of gelation of carbon nanotubes (CNTs)-hyaluronic acid (HA) mixtures. These materials are of great interest as functional biogels for future medical applications and tissue engineering. We show that CNTs can induce the gelation of noncovalently modified HA in water. This gelation is associated with a dynamical arrest of a liquid crystal phase separation, as shown by small-angle light scattering and polarized optical microscopy. This phenomenon is reminiscent of arrested phase separations in other colloidal systems in the presence of attractive interactions. The gelation time is found to strongly vary with the concentrations of both HA and CNTs. Near-infrared photoluminescence reveals that the CNTs remain individualized both in fluid and in gel states. It is concluded that the attractive forces interplay are likely weak depletion interactions and not strong van der Waals interactions which could promote CNT rebundling, as observed in other biopolymer-CNT mixtures. The present results clarify the remarkable efficiency of CNT at inducing the gelation of HA, by considering that CNTs easily phase separate as liquid crystals because of their giant aspect ratio.

  1. Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

    PubMed Central

    Lokeshwar, Vinata B.; Mirza, Summan; Jordan, Andre

    2016-01-01

    Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer therapy. Furthermore, as these members are also overexpressed in a variety of carcinomas, targeting of the HA family is clinically relevant. A variety of targeted approaches have been developed to target various HA family members, including small-molecule inhibitors and antibody and vaccine therapies. These treatment approaches inhibit HA-mediated intracellular signaling that promotes tumor cell proliferation, motility, and invasion, as well as induction of endothelial cell functions. Being nontoxic, nonimmunogenic, and versatile for modifications, HA has been used in nanoparticle preparations for the targeted delivery of chemotherapy drugs and other anticancer compounds to tumor cells through interaction with cell-surface HA receptors. This review discusses basic and clinical translational aspects of targeting each HA family member and respective treatment approaches that have been described in the literature. PMID:25081525

  2. LSMO Nanoparticles Coated by Hyaluronic Acid for Magnetic Hyperthermia

    NASA Astrophysics Data System (ADS)

    Chen, Yuanwei; Wang, Ying; Liu, Xi; Lu, Mai; Cao, Jiangwei; Wang, Tao

    2016-12-01

    Magnetic hyperthermia with the treating temperature range of 41-46 °C is an alternative therapy for cancer treatment. In this article, lanthanum strontium manganates (La1- x Sr x MnO3, 0.25 ≤ × ≤ 0.35) magnetic nanoparticles coated by hyaluronic acid (HA) which possesses the ability of targeting tumor cells were prepared by a simple hydrothermal method combined with a high-energy ball milling technique. The crystal structure, morphology, magnetic properties of the HA-coated magnetic nanoparticles (MNPs), and their heating ability under alternating magnetic field were investigated. It was found the HA-coated La0.7Sr0.3MnO3, with particle diameter of 100 nm, Curie temperature of 45 °C at a concentration 6 mg/ml, gave the optimal induction heating results. The heating temperature saturates at 45.7 °C, and the ESAR is 5.7 × 10-3 W/g · kHz · (kA/m2) which is much higher than other reported results.

  3. Hyaluronic acid in the management of osteoarthritis: injection therapies innovations

    PubMed Central

    Santilli, Valter; Paoloni, Marco; Mangone, Massimiliano; Alviti, Federica; Bernetti, Andrea

    2016-01-01

    Summary Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and progressive functional limitation. Viscosupplementation with intra-articular (IA) hyaluronic acid (HA) could be a treatment option in OA, however recommendations made in different international guidelines for the non-surgical management of OA are not always concordant with regard to the role of IA injection therapies. Results from a recent Italian Consensus Conference underline how IA-HA to treat OA represents a widely used therapy in Italy. Specifically high molecular weight HA, cross-linked HA, and mobile reticulum HA are considered very useful to treat the OA joints from a great number of expert in Italy. These kinds of HA could reduce the NSAIDs intake, furthermore high-molecular weight and mobile reticulum HA are considered to be able to delay or avoid a joint prosthetic implant. This mini review highlights the results obtained from the Italian Consensus Conference “Appropriateness of clinical and organizational criteria for intra-articular injection therapies in osteoarthritis” and give further indication about innovation in IA-HA therapies. PMID:27920810

  4. Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging.

    PubMed

    Yang, Xia; Sun, Yi; Kootala, Sujit; Hilborn, Jöns; Heerschap, Arend; Ossipov, Dmitri

    2014-09-22

    We report on a 19F labeled injectable hyaluronic acid (HA) hydrogel that can be monitored by both 1H and 19F MR imaging. The HA based hydrogel formed via carbazone reaction can be obtained within a minute by simple mixing of HA-carbazate and HA-aldehyde derivatized polymers. 19F contrast agent was linked to with carbazate and thiol dually functionalized HA via orthogonal Michael addition reaction which afforded cross-linkable and 19F labeled HA. The 19F labeling of HA polymer did not affect the mechanical properties of the formed hydrogel. As a result, the shape of a hydrogel sample could be imaged very well by both 1H MRI and high resolution 19F MRI. This hydrogel has high potential in clinical applications since it is injectable, biocompatible, and can be tracked in a minimally invasive manner. The present approach can be applied in preparation of injectable 19F labeled hydrogel biomaterials from other natural biomacromolecules.

  5. Viscoelasticity of hyaluronic acid-gelatin hydrogels for vocal fold tissue engineering

    PubMed Central

    Kazemirad, Siavash; Heris, Hossein K.; Mongeau, Luc

    2015-01-01

    Cross-linked injectable hyaluronic acid-gelatin hydrogels have remarkable viscoelastic and biological properties for vocal fold tissue engineering. Patient-specific tuning of the viscoelastic properties of this injectable biomaterial could improve tissue regeneration. The frequency-dependent viscoelasticity of cross-linked hyaluronic acid-gelatin hydrogels was measured as a function of the concentration of hyaluronic acid, gelatin, and cross-linker. Synthetic extracellular matrix hydrogels were fabricated using thiol-modified hyaluronic acid and gelatin, and cross-linked by Poly(ethylene glycol)diacrylate. A recently developed characterization method based on Rayleigh wave propagation was used to quantify the frequency-dependent viscoelastic properties of these hydrogels, including shear storage and loss moduli, over a broad frequency range; i.e., from 40 to 4000 Hz. The viscoelastic properties of the hydrogels increased with frequency. The storage and loss moduli values and the rate of increase with frequency varied with the concentrations of the constituents. The range of the viscoelastic properties of the hydrogels was within that of human vocal fold tissue obtained from in vivo and ex vivo measurements. Frequency-dependent parametric relations were obtained using a linear least-squares regression. The results are useful to better fine-tune the storage and loss moduli of hyaluronic acid-gelatin hydrogels by varying the concentrations of the constituents for use in patient-specific treatments. PMID:25728914

  6. Hyaluronic acid: analytical procedures for purity determination, polymerization degrees and comparative instrumental test 'in vivo'.

    PubMed

    Fiorentini, G; Becheroni, L; Iorio, G D

    1989-04-01

    Synopsis Recent studies have shown that hyaluronic acid is an important molecule in cosmetics, although there are different, sometimes controversial theories about its role. This work is an analytical contribution to the characterization and control of hyaluronic acid. The main techniques used are UV, GCP or SEC, IR and corneometry. Surveys conducted with the aid of these techniques have allowed a better knowledge of the molecular weight determination and of the uniform quality of commercial supplies. These procedures may be of application for quality control and promote further investigation on the biological tissular role played by hyaluronic acid in topical cosmetic products. The analytical results of a study of the evaluation of oil/water (o/w) emulsions containing hyaluronic acid of different origins are reported. The analytical data obtained from cutaneous hydration control apparatuses were compared statistically. The choice of hyaluronic acid, made through screening and evaluation by the abovementioned techniques, ensures the optimal formulation of the finished product and a quality standard of the active principle.

  7. The role of hyaluronic acid in SEB-induced acute lung inflammation.

    PubMed

    Uchakina, Olga N; Castillejo, Clara M; Bridges, Christy C; McKallip, Robert J

    2013-01-01

    We investigated the role of the extracellular matrix component, hyaluronic acid (HA) in SEB-induced ALI/ARDS. Intranasal exposure of mice to SEB led to a significant increase in the level of soluble hyaluronic acid in the lungs. Similarly, in an endothelial cell/spleen cell co-culture, SEB exposure led to significant increases in soluble levels of hyaluronic acid, cellular proliferation, and cytokine production compared with SEB-exposed spleen cells or endothelial cells alone. Exposure of SEB-activated spleen cells to hyaluronic acid led to increased cellular proliferation and increased cytokine production. SEB-induced cytokine production and proliferation in vitro were significantly reduced by the hyaluronic acid blocking peptide, Pep-1. Finally, treatment of SEB-exposed mice with Pep-1 significantly reduced SEB-induced ALI/ARDS, through reduction of cytokine production and numbers of lung inflammatory cells, compared to mice treated with a control peptide. Together, these results suggest the possibility of targeting HA for the treatment of SEB-induced ALI/ARDS.

  8. Complex coacervates of hyaluronic acid and lysozyme: effect on protein structure and physical stability.

    PubMed

    Water, Jorrit J; Schack, Malthe M; Velazquez-Campoy, Adrian; Maltesen, Morten J; van de Weert, Marco; Jorgensen, Lene

    2014-10-01

    Complex coacervates of hyaluronic acid and lysozyme, a model protein, were formed by ionic interaction using bulk mixing and were characterized in terms of binding stoichiometry and protein structure and stability. The complexes were formed at pH 7.2 at low ionic strength (6mM) and the binding stoichiometry was determined using solution depletion and isothermal titration calorimetry. The binding stoichiometry of lysozyme to hyaluronic acid (870 kDa) determined by solution depletion was found to be 225.9 ± 6.6 mol, or 0.1 bound lysozyme molecules per hyaluronic acid monomer. This corresponded well with that obtained by isothermal titration calorimetry of 0.09 bound lysozyme molecules per hyaluronic acid monomer. The complexation did not alter the secondary structure of lysozyme measured by Fourier-transform infrared spectroscopy overlap analysis and had no significant impact on the Tm of lysozyme determined by differential scanning calorimetry. Furthermore, the protein stability of lysozyme was found to be improved upon complexation during a 12-weeks storage study at room temperature, as shown by a significant increase in recovered protein when complexed (94 ± 2% and 102 ± 5% depending on the polymer-protein weight to weight ratio) compared to 89 ± 2% recovery for uncomplexed protein. This study shows the potential of hyaluronic acid to be used in combination with complex coacervation to increase the physical stability of pharmaceutical protein formulations.

  9. Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing.

    PubMed

    Trabucchi, E; Pallotta, S; Morini, M; Corsi, F; Franceschini, R; Casiraghi, A; Pravettoni, A; Foschi, D; Minghetti, P

    2002-01-01

    Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.

  10. Platelet dysfunction associated with Wilms tumor and hyaluronic acid.

    PubMed

    Bracey, A W; Wu, A H; Aceves, J; Chow, T; Carlile, S; Hoots, W K

    1987-03-01

    Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F.VIIIR:Ag, diminished F.VIIIR:WF (16.3%), F.VIII:C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels. To study the effects of HA on platelet function, we added HA to normal platelet-poor plasma (NPP), which rendered F.VIIIR:Ag undetectable; treatment of HA with hyaluronidase eliminated F.VIIIR:Ag assay interference caused by HA. F.VIII:C activity decreased in vitro when HA was mixed with normal platelet-poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA-spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27-136 dynes/cm2 over shear rates of 10-216 sec-1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F.VIIIR:Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.

  11. CD44 Binding to Hyaluronic Acid Is Redox Regulated by a Labile Disulfide Bond in the Hyaluronic Acid Binding Site

    PubMed Central

    Kellett-Clarke, Helena; Stegmann, Monika; Barclay, A. Neil; Metcalfe, Clive

    2015-01-01

    CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA), a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the–LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies. PMID:26379032

  12. The nonlinear viscoelasticity of hyaluronic acid and its role in joint lubrication.

    PubMed

    Zhang, Zhenhuan; Christopher, Gordon F

    2015-04-07

    Hyaluronic acid solutions have been widely studied due to their relevance to the rheological behavior of synovial fluid and joint lubrication. Ambulatory joint motion is typically large oscillatory deflections; therefore, large amplitude oscillatory shear strain experiments are used to examine the relevant non-linear viscoelastic properties of these solutions. Using the sequence of physical processes method to analyze data provides time dependent viscoelastic moduli, which exhibit a clear physiologically relevant behavior to hyaluronic acids non-linear viscoelasticity. In particular, it is seen that during peak strain/acceleration, the time dependent elastic modulus peaks and the loss modulus is at a minimum. The hyaluronic acid can provide an immediate elastic response to sudden forces, acting like a shock absorber during sudden changes in direction of motion or maximum deflection. However, during peak rate, the elastic modulus is at a minimum and the loss modulus is at a maximum, which provides greater efficacy to hydrodynamic shear lubrication.

  13. Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages.

    PubMed

    Fernandes Stefanello, Talitha; Szarpak-Jankowska, Anna; Appaix, Florence; Louage, Benoit; Hamard, Lauriane; De Geest, Bruno G; van der Sanden, Boudewijn; Nakamura, Celso Vataru; Auzély-Velty, Rachel

    2014-11-01

    Delivery systems for macrophages are particularly attractive since these phagocytic cells play a important role in immunological and inflammatory responses, also acting as host cells for microorganisms that are involved in deadly infectious diseases, such as leishmaniasis. Hyaluronic acid (HA) is specifically recognized by macrophages that are known to express HA receptors. Therefore, in this study, we focused on HA-based nanogels as drug carriers for these cells. The drug delivery was validated in an in vivo study on mice using intravital two-photon laser scanning microscopy. HA derivatives were modified with a biocompatible oligo(ethylene glycol)-based thermoresponsive polymer to form nanogels. These HA conjugates were readily prepared by varying the molar mass of initial HA and the degree of substitution via radical-mediated thiol-ene chemistry in aqueous solution. The derivatives were shown to self-assemble into spherical gel particles with diameters ranging from 150 to 214 nm above 37 °C. A poorly water-soluble two-photon dye was successfully loaded into the nanogels during this self-assembly process. In vitro cellular uptake tests using a RAW 264.7 murine macrophage cell line showed successful intracellular delivery of the hydrophobic dye. After intravenous injection in mice, the nanogels circulated freely in the blood but were rapidly phagocytized within 13 min by circulating macrophages and stored in the liver and spleen, as observed by two-photon microscopy. Benefit can be thus expected in using such a delivery system for the liver and spleen macrophage-associated diseases.

  14. Tranexamic Acid and Hyaluronate/Carboxymethylcellulose Create Cell Injury

    PubMed Central

    Yılmaz, Bayram; Dilbaz, Serdar; Üstün, Yusuf; Kumru, Selahattin

    2014-01-01

    Background and Objectives: Postoperative pelvic adhesions are associated with chronic pelvic pain, dyspareunia, and infertility. The aim of this study was to evaluate the adhesion prevention effects of tranexamic acid (TA) and hyaluronate/carboxymethylcellulose (HA/CMC) barrier in the rat uterine horn models on the basis of macroscopic and microscopic adhesion scores and histopathological as well as biochemical parameters of inflammation. Methods: Twenty-one Wistar rats were randomly divided into 3 groups. Ten lesions were created on the antimesenteric surface of both uterine horns by bipolar cautery. Three milliliters of 0.9% sodium chloride solution were administered in the control group. A single layer of 2 × 2 cm HA/CMC was plated in group 2. Two milliliters of TA was applied in the last group. All rats were sacrificed at postoperative day 21. Results: No significant difference was found among the control group, the HA/CMC group, and the TA group in terms of macro-adhesion score (P = .206) and microadhesion score (P = .056). No significant difference was found among the 3 groups in terms of inflammation score (P = .815) and inflammatory cell activity (P = .835). Malondialdehyde levels were significantly lower in the control group than in the TA group and HA/CMC group (P = .028). Superoxide dismutase and glutathione S-transferase activities were found to be higher in the control group than in the TA group (P = .005) and HA/CMC group (P = .009). Conclusions: TA and HA/CMC had no efficacy in preventing macroscopic or microscopic adhesion formation and decreasing inflammatory cell activity or inflammation score in our rat models. TA and HA/CMC increased the levels of free radicals and reduced the activities of superoxide dismutase and glutathione S-transferase enzymes, which act to reduce tissue injury. PMID:25392658

  15. Photopatterned collagen-hyaluronic acid interpenetrating polymer network hydrogels.

    PubMed

    Suri, Shalu; Schmidt, Christine E

    2009-09-01

    To engineer complex tissues, it is necessary to create hybrid scaffolds with micropatterned structural and biomechanical properties, which can closely mimic the intricate body tissues. The current report describes the synthesis of a novel photocrosslinkable interpenetrating polymeric network (IPN) of collagen and hyaluronic acid (HA) with precisely controlled structural and biomechanical properties. Both collagen and HA are present in crosslinked form in IPNs, and the two networks are entangled with each other. IPNs were also compared with semi-IPNs (SIPN), in which only collagen was in network form and HA chains were entangled in the collagen network without being photocrosslinked. Scanning electron microscopy images revealed that IPNs are denser than SIPNs, which results in their molecular reinforcement. This was further confirmed by rheological experiments. Because of the presence of the HA crosslinked network, the storage modulus of IPNs was almost two orders of magnitude higher than SIPNs. The degradation of the collagen-HA IPNs was slower than the SIPNs because of the presence of the crosslinked HA network. Increasing concentration of HA further altered the properties among IPNs. Cytocompatibility of IPNs was confirmed by Schwann cell and dermal fibroblasts adhesion and proliferation studies. We also fabricated patterned scaffolds with regions of IPNs and SIPNs within a bulk hydrogel, resulting in zonal distribution of crosslinking densities, viscoelasticities, water content and pore sizes at the micro- and macro-scales. With the ability to fine-tune the scaffold properties by performing structural modifications and to create patterned scaffolds, these hydrogels can be employed as potential candidates for regenerative medicine applications.

  16. Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits.

    PubMed

    Narurkar, Vic A; Fabi, Sabrina G; Bucay, Vivian W; Tedaldi, Ruth; Downie, Jeanine B; Zeichner, Joshua A; Butterwick, Kimberly; Taub, Amy; Kadoya, Kuniko; Makino, Elizabeth T; Mehta, Rahul C; Vega, Virginia L

    2016-01-01

    Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface. SkinMedica's HA5 Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles. Pre-clinical studies demonstrated that HA5 induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA5 application. Initial clinical studies showed that within 15 minutes of application, HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies

  17. Hyaluronic acid-coated liposomes for active targeting of gemcitabine.

    PubMed

    Arpicco, Silvia; Lerda, Carlotta; Dalla Pozza, Elisa; Costanzo, Chiara; Tsapis, Nicolas; Stella, Barbara; Donadelli, Massimo; Dando, Ilaria; Fattal, Elias; Cattel, Luigi; Palmieri, Marta

    2013-11-01

    The aim of this work was the preparation, characterization, and preliminary evaluation of the targeting ability toward pancreatic adenocarcinoma cells of liposomes containing the gemcitabine lipophilic prodrug [4-(N)-lauroyl-gemcitabine, C12GEM]. Hyaluronic acid (HA) was selected as targeting agent since it is biodegradable, biocompatible, and can be chemically modified and its cell surface receptor CD44 is overexpressed on various tumors. For this purpose, conjugates between a phospholipid, the 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and HA of two different low molecular weights 4800 Da (12 disaccharidic units) and 12,000 Da (32 disaccharidic units), were prepared, characterized, and introduced in the liposomes during the preparation. Different liposomal formulations were prepared and their characteristics were analyzed: size, Z potential, and TEM analyses underline a difference in the HA-liposomes from the non-HA ones. In order to better understand the HA-liposome cellular localization and to evaluate their interaction with CD44 receptor, confocal microscopy studies were performed. The results demonstrate that HA facilitates the recognition of liposomes by MiaPaCa2 cells (CD44(+)) and that the uptake increases with increase in the polymer molecular weight. Finally, the cytotoxicity of the different preparations was evaluated and data show that incorporation of C12GEM increases their cytotoxic activity and that HA-liposomes inhibit cell growth more than plain liposomes. Altogether, the results demonstrate the specificity of C12GEM targeting toward CD44-overexpressing pancreatic adenocarcinoma cell line using HA as a ligand.

  18. Hyaluronic acid enhances gene delivery into the cochlea.

    PubMed

    Shibata, Seiji B; Cortez, Sarah R; Wiler, James A; Swiderski, Donald L; Raphael, Yehoash

    2012-03-01

    Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.

  19. Hyaluronic acid-coated chitosan nanoparticles: molecular weight-dependent effects on morphology and hyaluronic acid presentation.

    PubMed

    Almalik, Abdulaziz; Donno, Roberto; Cadman, Christopher J; Cellesi, Francesco; Day, Philip J; Tirelli, Nicola

    2013-12-28

    Chitosan nanoparticles are popular carriers for the delivery of macromolecular payloads, e.g. nucleic acids. In this study, nanoparticles were prepared via complexation with triphosphate (TPP) anions and were successively coated with hyaluronic acid (HA). Key variables of the preparative process (e.g. chitosan and HA molecular weight) were optimised in view of the maximisation of loading with DNA, of the Zeta potential and of the dimensional stability, and the resulting particles showed excellent storage stability. We have focused on the influence of chitosan molecular weight on nanoparticle properties. Larger molecular weight increased their porosity (=decreased cross-link density), and this caused also larger dimensional changes in response to variations in osmotic pressure or upon drying. The dependency of nanoparticle porosity on chitosan molecular weight had a profound effect on the adsorption of HA on the nanoparticles; HA was apparently able to penetrate deeply into the more porous high molecular weight (684 kDa) chitosan nanoparticles, while it formed a corona around those composed of more densely cross-linked low molecular weight (25 kDa) chitosan. Atomic Force Microscopy (AFM) allowed not only to highlight the presence of this corona, but also to estimate its apparent thickness to about 20-30 nm (in a dry state). The different morphology has a significant effect on the way HA is presented to biomolecules, and this has specific relevance in relation to interactions with HA receptors (e.g. CD44) that influence kinetics and mechanism of nanoparticle uptake. Finally, it is worth to mention that chitosan molecular weight did not appear to greatly affect the efficiency of nanoparticle loading with DNA, but significantly influenced its chitosanase-triggered release, with high molecular chitosan nanoparticles seemingly more prone to degradation by this enzyme.

  20. Changes of synovial fluid protein concentrations in supra-patellar bursitis patients after the injection of different molecular weights of hyaluronic acid.

    PubMed

    Chen, Carl P C; Hsu, Chih Chin; Pei, Yu-Cheng; Chen, Ruo Li; Zhou, Shaobo; Shen, Hsuan-Chen; Lin, Shih-Cherng; Tsai, Wen Chung

    2014-04-01

    Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical settings, and in the aging population. Bursitis of the knee joint, especially when the volume of the synovial fluid is large enough, can compress and distend the nearby soft tissues, causing pain in the knee joint. Out of all the bursae surrounding the knee joint, supra-patellar bursitis is most often associated with knee pain. Treatment strategies in managing supra-patellar bursitis include the aspiration of joint synovial fluid and then followed by steroid injection into the bursa. When supra-patellar bursitis is caused by degenerative disorders, the concept of viscosupplementation treatment may be effective by injecting hyaluronic acid into the bursa. However, the rheology or the changes in the concentrations of proteins (biomarkers) that are related to the development of bursitis in the synovial fluid is virtually unexplored. Therefore, this study aimed to identify the concentration changes in the synovial fluid total protein amount and individual proteins associated with supra-patellar bursitis using the Bradford protein assay and western immunoglobulin methods. A total of 20 patients were divided into two groups with 10 patients in each group. One group received the high molecular weight hyaluronic acid product of Synvisc Hylan G-F 20 and the other group received the low molecular weight hyaluronic acid product of Hya-Joint Synovial Fluid Supplement once per week injection into the bursa for a total of 3 weeks. Significant decreases in the synovial fluid total protein concentrations were observed after the second dosage of high molecular weight hyaluronic acid injections. Apolipoprotein A-I, interleukin 1 beta, alpha 1 antitrypsin, and matrix metalloproteinase 1 proteins revealed a trend of decreasing western immunoblotting band densities after hyaluronic acid injections. The decreases in apolipoprotein A-I and interleukin 1 beta protein band densities were significant in the high

  1. Production and characterization of hyaluronic acid microparticles for the controlled delivery of growth factors using a spray/dehydration method.

    PubMed

    Babo, Pedro S; Reis, Rui L; Gomes, Manuela E

    2016-11-01

    Hyaluronic acid is the main polysaccharide present in the connective tissue. Besides its structural function as backbone of the extracellular matrix, hyaluronic acid plays staple roles in several biological processes including the modulation of inflammation and wound healing processes. The application of hyaluronic acid in regenerative medicine, either as cells and/or drug/growth factors delivery vehicles, relies on its ability to be cross-linked using a plethora of reactions, producing stable hydrogels. In this work, we propose a novel method for the production of hyaluronic acid microparticles that presents several advantages over others that have been used. Basically, droplets of hyaluronic acid solution produced with a nozzle are collected in an isopropanol dehydration bath, and stabilized after crosslinking with adipic acid dihydrazide, using a cabodiimide-based chemistry. The size and morphology of the hyaluronic acid microparticles produced by this method varied with the molecular weight and concentration of the hyaluronic acid solution, the nozzle chamber pressure, the distance between the nozzle and the crosslinking solution, and the number of crosslinking steps. The degree of crosslinking of the hyaluronic acid microparticles produced was tunable and allowed to control the rate of the degradation promoted by hyaluronidase. Moreover, the particles were loaded with platelet lysate, a hemoderivative rich in cytokines with interest for regenerative medicine applications. The hyaluronic acid microparticles showed potential to bind selectively to positively charged molecules, as the factors present in the platelet lysate. It is envisioned that these can be further released in a sustained manner by ion exchange or by the degradation of the hyaluronic acid microparticles matrix promoted by extracellular matrix remodeling.

  2. Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

    PubMed

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

    2016-05-01

    The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis.

  3. High and low molecular weight hyaluronic acid differentially influence macrophage activation.

    PubMed

    Rayahin, Jamie E; Buhrman, Jason S; Zhang, Yu; Koh, Timothy J; Gemeinhart, Richard A

    2015-07-13

    Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs.

  4. High and low molecular weight hyaluronic acid differentially influence macrophage activation

    PubMed Central

    Rayahin, Jamie E.; Buhrman, Jason S.; Zhang, Yu; Koh, Timothy J.; Gemeinhart, Richard A.

    2015-01-01

    Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs. PMID:26280020

  5. Intra-articular hyaluronic acid increases cartilage breakdown biomarker in patients with knee osteoarthritis.

    PubMed

    Gonzalez-Fuentes, Alexandra M; Green, David M; Rossen, Roger D; Ng, Bernard

    2010-06-01

    Intra-articular hyaluronic acid has been used in treatment of patients with knee osteoarthritis. Though its effect on pain has been well studied, it is not clear how it affects the articular cartilage. This is a preliminary study to evaluate the kinetics of urinary collagen type-II C-telopeptide (CTX-II) as a biomarker of collagen breakdown in response to intra-articular hyaluronic acid injection in patients with symptomatic knee osteoarthritis. Intra-articular injections of hyaluronan were administered to ten patients with symptomatic knee osteoarthritis. Urine collection for urinary CTX-II was obtained at baseline, before each injection and once every other week for a total of 6 months. Urine CTX-II was measured using a CartiLaps(c) ELISA kit. There was a statistically significant increase (p = 0.0136) in CTX-II a week after the third intra-articular injection of hyaluronic acid (6,216 ng/mmol +/- 4,428) compared with baseline (2,233 ng/mmol +/- 1,220). This increase in CTX-II was sustained throughout the entire 6 months follow-up period (repeated measures ANOVA, p < 0.015). This is the first study of changes in an osteoarthritis biomarker after intra-articular hyaluronic acid injections in patients with symptomatic knee osteoarthritis. Contrary to our initial hypothesis that CTX-II levels should decrease after intra-articular hyaluronic acid injections, we found a significant increase in urinary CTX-II levels that was sustained throughout the study. These observations suggest that intra-articular hyaluronic acid injections may accelerate cartilage breakdown in patients with symptomatic knee osteoarthritis. The responsible mechanisms are unknown and warrant further study.

  6. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

    PubMed

    Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2017-02-16

    (3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

  7. Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid.

    PubMed

    Estades-Rubio, Francisco J; Reyes-Martín, Alvaro; Morales-Marcos, Victor; García-Piriz, Mercedes; García-Vera, Juan J; Perán, Macarena; Marchal, Juan A; Montañez-Heredia, Elvira

    2017-03-17

    Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren-Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane(®)) and Group II with HA (Go-ON(®)). Patient's evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.

  8. Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid

    PubMed Central

    Estades-Rubio, Francisco J.; Reyes-Martín, Alvaro; Morales-Marcos, Victor; García-Piriz, Mercedes; García-Vera, Juan J.; Perán, Macarena; Marchal, Juan A.; Montañez-Heredia, Elvira

    2017-01-01

    Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren–Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane®) and Group II with HA (Go-ON®). Patient’s evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA. PMID:28304363

  9. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    SciTech Connect

    Kawano, Michinao; Ariyoshi, Wataru; Iwanaga, Kenjiro; Okinaga, Toshinori; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro; Nishihara, Tatsuji

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  10. Serum hyaluronic acid levels in patients with ankylosing spondylitis.

    PubMed

    Duruöz, Mehmet Tuncay; Turan, Yasemin; Cerrahoglu, Lale; Isbilen, Banu

    2008-05-01

    Our aim in this study was to investigate serum hyaluronic acid (HA) levels and the relationship between clinical parameters in ankylosing spondylitis (AS). Approximately 30 patients with AS and 30 healthy individuals were recruited in this study consecutively. Cross-sectional study was planned, and demographic, clinical, functional, radiological, and laboratory data of patients were evaluated. Disease activity, functional status, and quality of life were assessed, respectively, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Short-Form 36 (SF-36). Mander Enthesis Index (MEI) was used for evaluation of enthesis involvement. We examined serum concentrations of HA (ng/ml) in patients with AS and controls. The mean ages of patients and control group were 38.3 (SD=10.8) and 42.7 (SD=10.6) years, respectively. The mean of serum HA levels in AS patients was 40.4 (SD=34.8) ng/ml and in controls was 24.9 (SD=20.2). There was significant difference of HA levels between two groups (p=0.04). Furthermore, there was a significant correlation between HA level and distance of hand-floor (r=0.444, p=0.014), modified lumbar Schober's (r= -0.413, p=0.023), distance of chin to chest (r=0.436, p=0.016), right sacroiliit grade (r=0.601, p<0.001), left sacroiliit grade (r=0.610, p<0.001), C reactive protein level (r=0.404, p=0.027), albumin (r= -0.464, p=0.010), C3 (p=0.449, p=0.013), and IgA levels (r=0.369, p=0.045). However, there was no significant correlation between HA levels with MEI, BASFI, BASDAI, and SF-36 (p >or= 0.05). Serum HA level was significantly higher in AS patients than controls. However, there was no significant correlation between serum HA level and disease-specific measures as BASFI and BASDAI; it had significant relation with spinal mobility limitation, sacroiliitis, and laboratory parameters related with acute inflammation. The serum HA level may be a potential biomarker of axial

  11. Viscosupplementation in the hip: evaluation of hyaluronic acid formulations.

    PubMed

    van den Bekerom, M P J; Rys, B; Mulier, M

    2008-03-01

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

  12. Clinical benefit using sperm hyaluronic acid binding technique in ICSI cycles: a systematic review and meta-analysis.

    PubMed

    Beck-Fruchter, Ronit; Shalev, Eliezer; Weiss, Amir

    2016-03-01

    The human oocyte is surrounded by hyaluronic acid, which acts as a natural selector of spermatozoa. Human sperm that express hyaluronic acid receptors and bind to hyaluronic acid have normal shape, minimal DNA fragmentation and low frequency of chromosomal aneuploidies. Use of hyaluronic acid binding assays in intracytoplasmic sperm injection (ICSI) cycles to improve clinical outcomes has been studied, although none of these studies had sufficient statistical power. In this systematic review and meta-analysis, electronic databases were searched up to June 2015 to identify studies of ICSI cycles in which spermatozoa able to bind hyaluronic acid was selected. The main outcomes were fertilization rate and clinical pregnancy rate. Secondary outcomes included cleavage rate, embryo quality, implantation rate, spontaneous abortion and live birth rate. Seven studies and 1437 cycles were included. Use of hyaluronic acid binding sperm selection technique yielded no improvement in fertilization and pregnancy rates. A meta-analysis of all available studies showed an improvement in embryo quality and implantation rate; an analysis of prospective studies only showed an improvement in embryo quality. Evidence does not support routine use of hyaluronic acid binding assays in all ICSI cycles. Identification of patients that might benefit from this technique needs further study.

  13. [Specific interaction study in collagen/hyaluronic acid blends by two-dimensional infrared correlation spectroscopy].

    PubMed

    Tan, Qing-Tian; Tian, Zhen-Hua; Li, Guo-Ying

    2011-04-01

    Conformational changes and specific interactions in the collagen/hyaluronic acid blends were studied by two-dimensional infrared correlation spectroscopy with the interruption of the component of hyaluronic acid in collagen/ hyaluronic acid blends. It was found that the synchronous cross-peaks, derived from stretching vibrations of C=O at 1 694 cm(-1), wagging of N-H at 1 524 cm(-1) and in-plane deformation of N-H at 1 241 cm(-1) of collagen, were indicative of local conformational changes of collagen. The synchronous negative cross-peak between stretching vibrations of C-OH of hyaluronic acid at 1 045 cm(-1) and streching vibrations of C=O of collagen at 1 694 cm(-1) suggested that the interaction of hydrogen bonding existing between O-H of HA and C=O of collagen with the content of HA varied from 0% to 50%. With the content of HA more than 50%, the cross-peak at 1 045 cm(-1) disappeared in synchronous correlation spectra while the intensity of cross-peak at (1 694, 1 524), (1 694, 1 241), (1 524, 1 241) increased, which indicated that no interaction was found between O-H of HA and collagen, however, the interactions of hydrogen bonding existed between C=O of HA and N-H of collagen, resulting in the conformational changes of collagen.

  14. A novel biocompatible hyaluronic acid-chitosan hybrid hydrogel for osteoarthrosis therapy.

    PubMed

    Kaderli, S; Boulocher, C; Pillet, E; Watrelot-Virieux, D; Rougemont, A L; Roger, T; Viguier, E; Gurny, R; Scapozza, L; Jordan, O

    2015-04-10

    A conventional therapy for the treatment of osteoarthrosis is intra-articular injection of hyaluronic acid, which requires repeated, frequent injections. To extend the viscosupplementation effect of hyaluronic acid, we propose to associate it with another biopolymer in the form of a hybrid hydrogel. Chitosan was chosen because of its structural similarity to synovial glycosaminoglycans, its anti-inflammatory effects and its ability to promote cartilage growth. To avoid polyelectrolyte aggregation and obtain transparent, homogeneous gels, chitosan was reacetylated to a 50% degree, and different salts and formulation buffers were investigated. The biocompatibility of the hybrid gels was tested in vitro on human arthrosic synoviocytes, and in vivo assessments were made 1 week after subcutaneous injection in rats and 1 month after intra-articular injection in rabbits. Hyaluronic acid-chitosan polyelectrolyte complexes were prevented by cationic complexation of the negative charges of hyaluronic acid. The different salts tested were found to alter the viscosity and thermal degradation of the gels. Good biocompatibility was observed in rats, although the calcium-containing formulation induced calcium deposits after 1 week. The sodium chloride formulation was further tested in rabbits and did not show acute clinical signs of pain or inflammation. Hybrid HA-Cs hydrogels may be a valuable alternative viscosupplementation agent.

  15. Synthesis, Structural and Micromechanical Properties of 3D Hyaluronic Acid-Based Cryogel Scaffolds.

    PubMed

    Oelschlaeger, C; Bossler, F; Willenbacher, N

    2016-02-08

    In this study, macroporous, elastic, three-dimensional scaffolds formed of hyaluronic acid mixed with ethylene glycol diglycidyl ether as a chemical cross-linker have been prepared by cryogelation for application in tissue engineering. These cryogels are characterized by large interconnected pores of size ∼50-300 μm and pore wall thickness of ∼5-30 μm as determined from confocal microscopy images. Variation of pH, freezing temperature, and polymerization time allows for control of pore size and shape as well as matrix thickness. These structural properties then determine mechanical strength as well as swelling capacity. Furthermore, increasing hyaluronic acid concentration decreases cryogel pore size, reduces swelling properties, and reinforces mechanical properties. On the other hand, decreasing cross-linker concentration, at a constant hyaluronic acid concentration, increases pore size and swelling capacity but provides less rigidity. Additionally, for the first time, local elastic properties of the polymer matrix and viscous properties of the pores have been characterized using multiple particle tracking microrheology. Local matrix elasticity, relaxation time of hyaluronic acid chains, and the degree of heterogeneity are discussed in detail. These latter properties are crucial for the development of new tissue engineering constructs and will help to understand how local matrix viscoelasticity affects cell cultivation. Finally, elastic moduli obtained in bulk rheology are much higher than corresponding values deduced from microrheology. This discrepancy might be explained by the formation of very highly cross-linked cores in the network where no tracer particle can penetrate.

  16. A blanching technique for intradermal injection of the hyaluronic acid Belotero.

    PubMed

    Micheels, Patrick; Sarazin, Didier; Besse, Stéphanie; Sundaram, Hema; Flynn, Timothy C

    2013-10-01

    With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.

  17. A case of diffuse alveolar hemorrhage associated with hyaluronic acid dermal fillers

    PubMed Central

    Basora, Jose F.; Fernandez, Ricardo; Gonzalez, Modesto; Adorno, Jose

    2014-01-01

    Patient: Male, 25 Final Diagnosis: Diffuse alveolar hemorrhage Symptoms: Cough dry • short of breath Medication: — Clinical Procedure: — Specialty: — Objective: Unusual clinical course Background: Hyaluronic acid is a substance that is naturally present in the human body, especially in joints and eyes. Hyaluronic acid injectable gels have been available for the general market since 2003 as cosmetic dermal fillers and skin boosters. Diffuse alveolar hemorrhage is an acute event that threatens the life of the patient and can lead to pulmonary fibrosis. Alveolar hemorrhage associated with hyaluronic acid dermal fillers is an entity that to the best of our knowledge has never been described in the medical literature. Case Report: We describe a patient who presented with dyspnea and cough after a subcutaneous injection of hyaluronic acid, with radiographic abnormalities including ground glass opacities and consolidation. The patient underwent flexible bronchoscopy and was diagnosed with diffuse alveolar hemorrhage. Conclusions: This case emphasizes that this life threatening condition may occur with the use of this medication and physicians must be aware of this disorder, as early recognition and management can reduce morbidity. PMID:24826208

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

    PubMed

    Kim, Deok-Yeol; Namgoong, Sik; Han, Seung-Kyu; Won, Chang-Hoon; Jeong, Seong-Ho; Dhong, Eun-Sang; Kim, Woo-Kyung

    2015-07-01

    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.

  19. Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration.

    PubMed

    Su, Wen-Yu; Chen, Yu-Chun; Lin, Feng-Huei

    2010-08-01

    Injectable hydrogel allows irregular surgical defects to be completely filled, lessens the risk of implant migration, and minimizes surgical defects due to the solution-gel state transformation. Here, we first propose a method for preparing oxidized hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) injectable hydrogel by chemical cross-linking under physiological conditions. Fourier transform infrared spectrometry and trinitrobenzene sulfonate assay were used to confirm the oxidation of hyaluronic acid. Rheological properties were measured to evaluate the working ability of the hydrogel for further clinical application. The oxi-HA/ADH in situ forming hydrogel can transform from liquid form into a gel-like matrix within 3-8 min, depending on the operational temperature. Furthermore, hydrogel degradation and cell assessment is also a concern for clinical application. Injectable oxi-HA/ADH8 hydrogel can maintain its gel-like state for at least 5 weeks with a degradation percentage of 40%. Importantly, oxi-HA/ADH8 hydrogel can assist in nucleus pulposus cell synthesis of type II collagen and aggrecan mRNA gene expression according to the results of real-time PCR analysis, and shows good biocompatibility based on cell viability and cytotoxicity assays. Based on the results of the current study, oxi-HA/ADH hydrogel may possess several advantages for future application in nucleus pulposus regeneration.

  20. An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute.

    PubMed

    Su, Wen-Yu; Chen, Ko-Hua; Chen, Yu-Chun; Lee, Yen-Hsien; Tseng, Ching-Li; Lin, Feng-Huei

    2011-01-01

    Vitrectomy is a common procedure for treating ocular-related diseases. The surgery involves removing the vitreous humor from the center of the eye, and vitreous substitutes are needed to replace the vitreous humor after vitrectomy. In the present study, we developed a colorless, transparent and injectable hydrogel with appropriate refractive index as a vitreous substitute. The hydrogel is formed by oxidated hyaluronic acid (oxi-HA) cross-linked with adipic acid dihydrazide (ADH). Hyaluronic acid (HA) was oxidized by sodium periodate to create aldehyde functional groups, which could be cross-linked by ADH. The refractive index of this hydrogel ranged between 1.3420 and 1.3442, which is quite similar to human vitreous humor (1.3345). The degradation tests demonstrated that the hydrogel could maintain the gel matrix over 35 days, depending on the ADH concentration. In addition, the cytotoxicity was evaluated on retina pigmented epithelium (RPE) cells cultivated following the ISO standard (tests for in vitro cytotoxicity), and the hydrogel was found to be non-toxic. In a preliminary animal study, the oxi-HA/ADH hydrogel was injected into the vitreous cavity of rabbit eyes. The evaluations of slit-lamp observation, intraocular pressure, cornea thickness and histological examination showed no significant abnormal biological reactions for 3 weeks. This study suggests that the injectable oxi-HA/ADH hydrogel should be a potential vitreous substitute.

  1. Hyaluronic acid and its use as a "rejuvenation" agent in cosmetic dermatology.

    PubMed

    Andre, Pierre

    2004-12-01

    Since 1996, hyaluronic acid (HA) has been launched onto the market in Europe. Since then, different companies proposed their HAs. Biomatrix (NJ, USA) proposes an animal-derived HA (from rooster comb). Q-Med AB (Uppsala, Sweden) and LEA-DERM (Paris, France) are the main companies to have a nonanimal HA. HA is produced by bacterial fermentation from a specific strain of streptococci. HA has no species specificity and theoretically has no risk of allergy. No skin testing is necessary before injecting because HA is a biodegradable agent. To be utilized as a filler agent for improving wrinkles, scars, or increasing volumes, HA must be stabilized to obtain a sufficient half-life. Process of stabilization varies, according to each manufacturer. This explains the differences in longevity and in viscosity of the different products. Several HAs are suitable to fine lines, to deep wrinkles/folds, or to increase volume. A new indication for "rejuvenation" is injection into the superficial dermis and epidermis. The HA (stabilized or not) is not used to fill in but rather to hydrate and finally to rejuvenate the skin. This procedure must be repeated at intervals of a few weeks or months. If HA is the safest filler agent in cosmetic indications today, some rare side effects may appear and must be known to inform patients. Most of these complications are not severe and will disappear when the product is degraded.

  2. The association between radiographic embrasure morphology and interdental papilla reconstruction using injectable hyaluronic acid gel

    PubMed Central

    2016-01-01

    Purpose The purpose of this study was to evaluate the clinical efficacy of enhancing deficient interdental papilla with hyaluronic acid gel injection by assessing the radiographic anatomical factors affecting the reconstruction of the interdental papilla. Methods Fifty-seven treated sites from 13 patients (6 males and 7 females) were included. Patients had papillary deficiency in the upper anterior area. Prior to treatment, photographic and periapical radiographic standardization devices were designed for each patient. A 30-gauge needle was used with an injection-assistance device to inject a hyaluronic acid gel to the involved papilla. This treatment was repeated up to 5 times every 3 weeks. Patients were followed up for 6 months after the initial gel application. Clinical photographic measurements of the black triangle area (BTA), height (BTH), and width (BTW) and periapical radiographic measurements of the contact point and the bone crest (CP-BC) and the interproximal distance between roots (IDR) were undertaken using computer software. The interdental papilla reconstruction rate (IPRR) was calculated to determine the percentage change of BTA between the initial and final examination and the association between radiographic factors and the reconstruction of the interdental papilla by means of injectable hyaluronic acid gel were evaluated. Results All sites showed improvement between treatment examinations. Thirty-six sites had complete interdental papilla reconstruction and 21 sites showed improvement ranging from 19% to 96%. The CP-BC correlated with the IPRR. More specifically, when the CP-BC reached 6 mm, virtually complete interdental papilla reconstruction via injectable hyaluronic acid gel was achieved. Conclusions These results suggest that the CP-BC is closely related to the efficacy of hyaluronic acid gel injection for interdental papilla reconstruction. PMID:27588217

  3. Isolation and characterization of hyaluronic acid from the liver of marine stingray Aetobatus narinari.

    PubMed

    Sadhasivam, Giji; Muthuvel, Arumugam; Pachaiyappan, Abirami; Thangavel, Balasubramanian

    2013-03-01

    Although hyaluronic acid research pursuits ahead in exploring its biomedical perspective, very limited investigations were carried out in their isolation shape view point, furthermore, most of the investigations were targeted towards the terrestrial source. To swerve from that, the present study was projected through the marine superstore, where in high molecular weight hyaluronic acid of 13, 65,863 Da was isolated from the liver of stingray Aetobatus narinari. The purified HA was confirmed at the preliminary level by their stains all dye binding nature. Their analytical composition including carbon, hydrogen, nitrogen, N-acetyl glucosamine, glucuronic acid contents was analysed. The HA was characterized by agarose-gel electrophoresis, FTIR, HPTLC, and (1)H NMR. The DPPH radical scavenging activity of HA and its reducing power was evident to all the tested concentrations, but lower than that of ascorbic acid. HA showed significant inhibition against the proliferation of cells, substantiating its influence in regulation of cell functions.

  4. Viscosupplementation in the hip: evaluation of hyaluronic acid formulations

    PubMed Central

    van den Bekerom, M. P. J.; Rys, B.

    2007-01-01

    This study compares three different hyaluronate formulations and evaluates functionality, time of satisfactory pain relief and also the delay in performing a total hip arthroplasty. One hundred and twenty patients (126 hips) received viscosupplementation with one of the three hyaluronate formulations. All patients were candidate for surgical treatment with a total hip arthroplasty. Three different products were consecutively used: Adant®, Synocrom® or Synvisc®. Patients were assessed 6 weeks after each infiltration using Visual Analogue Scale and Harris Hip Score. The Harris Hip Score increased significantly in two of the three groups compared to baseline, but no statistical significant difference was noted between the groups. Viscosupplementation provides significant pain reduction in two of the three groups. There is no significant difference in duration of the effect of the first infiltration between the three groups. The positive effect was still ongoing at the end point of the study in 46 hips: 51% of the patients did not undergo total hip arthroplasty, 3 years after viscosupplementation. PMID:17572901

  5. Optimal conjugation of catechol group onto hyaluronic acid in coronary stent substrate coating for the prevention of restenosis

    PubMed Central

    Lih, Eugene; Choi, Seul Gi; Ahn, Dong June; Joung, Yoon Ki; Han, Dong Keun

    2016-01-01

    Although endovascular stenting has been used as an interventional therapy to treat cardio- and cerebro-vascular diseases, it is associated with recurrent vascular diseases following stent thrombosis and in-stent restenosis. In this study, a metallic stent was coated with dopamine-conjugated hyaluronic acid with different ratios of catechol group to improve hemocompatibility and re-endothelialization. Especially, we were interested in how much amount of catechol group is appropriate for the above-mentioned purposes. Therefore, a series of dopamine-conjugated hyaluronic acid conjugates with different ratios of catechol group were synthesized via a carbodiimide coupling reaction. Dopamine-conjugated hyaluronic acid conjugates were characterized with 1H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the amount of catechol group in dopamine-conjugated hyaluronic acid was measured by ultraviolet spectrometer. Co-Cr substrates were polished and coated with various dopamine-conjugated hyaluronic acid conjugates under pH 8.5. Dopamine-conjugated hyaluronic acid amounts on the substrate were quantified by micro-bicinchoninic acid assay. Surface characteristics of dopamine-conjugated hyaluronic-acid-coated Co-Cr were evaluated by water contact angle, scanning electron microscopy, and atomic force microscopy. The hemocompatibility of the surface-modified substrates was assessed by protein adsorption and platelet adhesion tests. Adhesion and activation of platelets were confirmed with scanning electron microscopy and lactate dehydrogenase assay. Human umbilical vein endothelial cells were cultured on the substrates, and the viability, adhesion, and proliferation were investigated through cell counting kit-8 assay and fluorescent images. Obtained results demonstrated that optimal amounts of catechol group (100 µmol) in the dopamine-conjugated hyaluronic acid existed in terms of various properties such as hemocompatibility and cellular responses

  6. Optimal conjugation of catechol group onto hyaluronic acid in coronary stent substrate coating for the prevention of restenosis.

    PubMed

    Lih, Eugene; Choi, Seul Gi; Ahn, Dong June; Joung, Yoon Ki; Han, Dong Keun

    2016-01-01

    Although endovascular stenting has been used as an interventional therapy to treat cardio- and cerebro-vascular diseases, it is associated with recurrent vascular diseases following stent thrombosis and in-stent restenosis. In this study, a metallic stent was coated with dopamine-conjugated hyaluronic acid with different ratios of catechol group to improve hemocompatibility and re-endothelialization. Especially, we were interested in how much amount of catechol group is appropriate for the above-mentioned purposes. Therefore, a series of dopamine-conjugated hyaluronic acid conjugates with different ratios of catechol group were synthesized via a carbodiimide coupling reaction. Dopamine-conjugated hyaluronic acid conjugates were characterized with (1)H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the amount of catechol group in dopamine-conjugated hyaluronic acid was measured by ultraviolet spectrometer. Co-Cr substrates were polished and coated with various dopamine-conjugated hyaluronic acid conjugates under pH 8.5. Dopamine-conjugated hyaluronic acid amounts on the substrate were quantified by micro-bicinchoninic acid assay. Surface characteristics of dopamine-conjugated hyaluronic-acid-coated Co-Cr were evaluated by water contact angle, scanning electron microscopy, and atomic force microscopy. The hemocompatibility of the surface-modified substrates was assessed by protein adsorption and platelet adhesion tests. Adhesion and activation of platelets were confirmed with scanning electron microscopy and lactate dehydrogenase assay. Human umbilical vein endothelial cells were cultured on the substrates, and the viability, adhesion, and proliferation were investigated through cell counting kit-8 assay and fluorescent images. Obtained results demonstrated that optimal amounts of catechol group (100 µmol) in the dopamine-conjugated hyaluronic acid existed in terms of various properties such as hemocompatibility and cellular responses.

  7. The effect of hyaluronic acid (Cicatridine) on healing and regeneration of the uterine cervix and vagina and vulvar dystrophy therapy.

    PubMed

    Markowska, J; Madry, R; Markowska, A

    2011-01-01

    Procedures aimed at the treatment of precancerous lesions and ectopia on the uterine cervix are frequently linked to lesions of anatomical structures. The application of hyaluronic acid (Cicatridine vaginal ovules) promotes accelerated healing of the uterine cervix and acquisition of a normal shape in the uterine cervix canal. Local application of hyaluronic acid in the vagina following radiotherapy due to cancer in the uterine cervix or endometrium favourably affects the healing of post-irradiation lesions in the vagina and improves quality of life. Over 90% of patients responded positively to the application of hyaluronic acid in the form of a cream on dystrophic lesions in the vulva. Hyaluronic acid aids the healing process of post-procedural wounds in the uterine cervix, following radiotherapy applied due to cancer of the uterine cervix, endometrium and in vulvar dystrophy.

  8. 3D composites based on the blends of chitosan and collagen with the addition of hyaluronic acid.

    PubMed

    Sionkowska, Alina; Kaczmarek, Beata; Lewandowska, Katarzyna; Grabska, Sylwia; Pokrywczyńska, Marta; Kloskowski, Tomasz; Drewa, Tomasz

    2016-08-01

    3D porous composites based on blends of chitosan, collagen and hyaluronic acid were obtained through the lyophilization process. Mechanical properties, swelling behavior and thermal stability of the blends were studied. Moreover, SEM images were taken and the structure of the blends was studied. Biological properties of the materials obtained were investigated by analyzing of proliferation rate of fibroblast cells incubated with biomaterial extract using MTT assay (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide). The results showed that the properties of 3D composites based on the blends of chitosan and collagen were altered after the addition 1%, 2% and 5% of hyaluronic acid. Mechanical properties and thermal stability of chitosan/collagen blends were improved in the presence of hyaluronic acid in the composite. New 3D materials based on the blends of chitosan, collagen and hyaluronic acid were non-toxic and did not significantly affect cell morphology.

  9. Nasal Reshaping with Hyaluronic Acid: An Alternative or Complement to Surgery

    PubMed Central

    2016-01-01

    Background: Rhinoplasty has traditionally been preferred for correction of nasal defects. Long-term clinical experience with hyaluronic acid (HA) injection as an alternative or complement to rhinoplasty is presented. Methods: A retrospective review of the author’s clinical experience with HA gel for nasal reshaping from 1997 to 2012 was conducted, with treatments performed during 1998, 2005, and 2012 selected for detailed review. Results: More than 250 patients were treated for nasal reshaping with HA since 1997. In addition to being a complement to surgery, HA injection successfully addressed nasal defects that would have been difficult to correct surgically. The effect persisted for >1 year in most patients (>5 y in some patients), with individual variations. No serious complications occurred. When comparing the 3 years reviewed in detail, new indications for nasal reshaping with HA gel became evident over time, which was also reflected by the increase in number of patients treated (1998: n = 2; 2005: n = 22; 2012: n = 51). Of these patients, 55 (73%) received HA injection instead of rhinoplasty, 20 (27%) received HA injection after rhinoplasty, and 5 (7%) underwent rhinoplasty after HA injection. The mean injection volume was 0.4 mL HA gel/treatment. All patients were satisfied with the primary outcome of treatment. Retreatment was performed in 32 patients (43%). Conclusions: Injection of HA gel is a valuable tool for nasal reshaping. It can also be used for correction of minor postrhinoplasty defects in appropriate patients. PMID:27975025

  10. Prostate Hypofractionated Radiation Therapy: Injection of Hyaluronic Acid to Better Preserve The Rectal Wall

    SciTech Connect

    Chapet, Olivier; Udrescu, Corina; Devonec, Marian; Tanguy, Ronan; Sotton, Marie-Pierre; Enachescu, Ciprian; Colombel, Marc; Azria, David; Jalade, Patrice; Ruffion, Alain

    2013-05-01

    Purpose: The aim of this study was to evaluate the contribution of an injection of hyaluronic acid (HA) between the rectum and the prostate for reducing the dose to the rectal wall in a hypofractionated irradiation for prostate cancer. Methods and Materials: In a phase 2 study, 10 cc of HA was injected between the rectum and prostate. For 16 patients, the same intensity modulated radiation therapy plan (62 Gy in 20 fractions) was optimized on 2 computed tomography scans: CT1 (before injection) and CT2 (after injection). Rectal parameters were compared: dose to 2.5 cc (D2.5), 5 cc (D5), 10 cc (D10), 15 cc (D15), and 20 cc (D20) of rectal wall and volume of rectum covered by the 90% isodose line (V90), 80% (V80), 70% (V70), 60% (V60), and 50% (V50). Results: The mean V90, V80, V70, V60, and V50 values were reduced by 73.8% (P<.0001), 55.7% (P=.0003), 43.0% (P=.007), 34% (P=.002), and 25% (P=.036), respectively. The average values of D2.5, D5, D10, D15, and D20 were reduced by 8.5 Gy (P<.0001), 12.3 Gy (P<.0001), 8.4 Gy (P=.005), 3.7 Gy (P=.026), and 1.2 Gy (P=.25), respectively. Conclusions: The injection of HA significantly limited radiation doses to the rectal wall.

  11. [HYALURONIC ACID: STRUCTURE, FUNCTIONS, THE POSSIBILITES OF APPLYING IN THE COMPLEX TREATMENT OF THE TEMPOROMANDIBULAR JOINT DISEASES. A REWIEW].

    PubMed

    Volovar, O S; Malanchuk, V A; Kryzhanivska, O A

    2014-01-01

    Over the last decade the use of hyaluronic acid has become increasingly important in treatment of degenerative disorders of the temporomandibular joint. Urgency is caused by numerous studies in biology and pharmacology on structure and function of hyaluronic acid and its influence on the processes of repair damaged bone and articular cartilage restoration, as well as the positive long-term results of treatment in this group of patients.

  12. Design of aqueous two-phase systems for purification of hyaluronic acid produced by metabolically engineered Lactococcus lactis.

    PubMed

    Rajendran, Vivek; Puvendran, Kirubhakaran; Guru, Bharath Raja; Jayaraman, Guhan

    2016-02-01

    Hyaluronic acid has a wide range of biomedical applications and its commercial value is highly dependent on its purity and molecular weight. This study highlights the utility of aqueous two-phase separation as a primary recovery step for hyaluronic acid and for removal of major protein impurities from fermentation broths. Metabolically engineered cultures of a lactate dehydrogenase mutant strain of Lactococcus lactis (L. lactis NZ9020) were used to produce high-molecular-weight hyaluronic acid. The cell-free fermentation broth was partially purified using a polyethylene glycol/potassium phosphate system, resulting in nearly 100% recovery of hyaluronic acid in the salt-rich bottom phase in all the aqueous two-phase separation experiments. These experiments were optimized for maximum removal of protein impurities in the polyethylene glycol rich top phase. The removal of protein impurities resulted in substantial reduction of membrane fouling in the subsequent diafiltration process, carried out with a 300 kDa polyether sulfone membrane. This step resulted in considerable purification of hyaluronic acid, without any loss in recovery and molecular weight. Diafiltration was followed by an adsorption step to remove minor impurities and achieve nearly 100% purity. The final hyaluronic acid product was characterized by Fourier-transform IR and NMR spectroscopy, confirming its purity.

  13. Surface and thermal properties of collagen/hyaluronic acid blends containing chitosan.

    PubMed

    Lewandowska, Katarzyna; Sionkowska, Alina; Grabska, Sylwia; Kaczmarek, Beata

    2016-11-01

    The structure and surface properties of binary and ternary blends containing collagen (Coll), hyaluronic acid (HA) and chitosan (Ch) were investigated by contact angle measurements, thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and atomic force microscopy (AFM). Thin films of Coll/HA and Coll/HA/Ch blends have been formed by casting methods from aqueous acid solutions. The surface roughness, hydrophobic/hydrophilic character and thermal stability of Coll/HA were changed after addition of chitosan. Thermal stability of binary blends increase upon the addition of chitosan. The results of contact angle and the surface free energy revealed that hyaluronic acid films are more polar than collagen and chitosan films. The surface energy and its polar and dispersive components of binary and ternary blends were calculated and more hydrophilic films were produced by the addition of HA and chitosan, also resulting in more thermally stabile materials. These results demonstrate that collagen interacts with hyaluronic acid and chitosan changing the surface properties of polymer films.

  14. Effective treatment of acne scars using pneumatic injection of hyaluronic acid.

    PubMed

    Patel, Tapan; Tevet, Oren

    2015-01-01

    Acne scars remain a challenging condition to treat despite multiple currently available technologies. This study evaluated the clinical efficacy and safety of pneumatic injections of Hyaluronic Acid in the treatment of acne scars. Two patients (Fitzpatrick skin type IV-V) with acne scars received two sessions of pneumatic, needleless injections of crosslinked hyaluronic acid (HA) at 4-week intervals. The treatment response was assessed by comparing pre- and 3-month posttreatment clinical photography. The patients' acne scar grade improved from 2 to 1 in the first case, and 3 to 2 in the second case, based on independent physician assessment. Patient degree of satisfaction was similar to the physicians' assessment. No significant adverse events were noted. We conclude that pneumatic injection technology to deliver HA to the tissue is an effective and safe method for improving acne scars, even in patients with dark complexion.

  15. Hyaluronic acid nanogels with enzyme-sensitive cross-linking group for drug delivery.

    PubMed

    Yang, Chenchen; Wang, Xin; Yao, Xikuang; Zhang, Yajun; Wu, Wei; Jiang, Xiqun

    2015-05-10

    A methacrylation strategy was employed to functionalize hyaluronic acid and prepare hyaluronic acid (HA) nanogels. Dynamic light scattering, zeta potential analyzer and electron microscopy were utilized to characterize the nanogels and their enzyme-degradability in vitro. It was found that these nanogels had a spherical morphology with the diameter of about 70nm, and negative surface potential. When doxorubicin (DOX) was loaded into the nanogels, the diameter decreased to approximately 50nm with a drug loading content of 16% and encapsulation efficiency of 62%. Cellular uptake examinations showed that HA nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs) which both overexpress CD44 receptor. Near-infrared fluorescence imaging, biodistribution and penetration examinations in tumor tissue indicated that the HA nanogels could efficiently accumulate and penetrate the tumor matrix. In vivo antitumor evaluation found that DOX-loaded HA nanogels exhibited a significantly superior antitumor effect.

  16. Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation.

    PubMed

    Zaboronok, A; Yamamoto, T; Nakai, K; Yoshida, F; Uspenskii, S; Selyanin, M; Zelenetskii, A; Matsumura, Akira

    2015-12-01

    Hyaluronic acid (HA), a nonimmunogenic, biocompatible polymer found in different biological tissues, has the potential to attach to CD44 receptors on the surface of certain cancer cells, where the receptor is overexpressed compared with normal cells. Boron-hyaluronic acid (BHA) was tested for its feasibility as a potential agent for BNCT. BHA with low-viscosity 30 kDa HA could be administered by intravenous injection. The compound showed a certain degree of cytotoxicity and accumulation in C6 rat glioma cells in vitro. Instability of the chelate bonds between boron and HA and/or insufficient specificity of CD44 receptors on C6 cells to BHA could account for the insufficient in vitro accumulation. To ensure the future eligibility of BHA for BNCT experiments, using alternative tumor cell lines and chemically securing the chelate bonds or synthesizing BHA with boron covalently attached to HA might be required.

  17. Electrophoretic deposition and electrochemical behavior of novel graphene oxide-hyaluronic acid-hydroxyapatite nanocomposite coatings

    NASA Astrophysics Data System (ADS)

    Li, Ming; Liu, Qian; Jia, Zhaojun; Xu, Xuchen; Shi, Yuying; Cheng, Yan; Zheng, Yufeng; Xi, Tingfei; Wei, Shicheng

    2013-11-01

    Novel ternary graphene oxide-hyaluronic acid-hydroxyapatite (GO-HY-HA) nanocomposite coatings were prepared on Ti substrate using anodic electrophoretic deposition (EPD). Hyaluronic acid was employed as charging additive and dispersion agent during EPD. The kinetics and mechanism of the deposition, and the microstructure of the coated samples were investigated using scanning electron microscopy, X-ray diffraction, Raman spectrum, thermo-gravimetric analysis, and microscopic Fourier transform infrared analysis. The results showed that the addition of GO sheets into the HY-HA suspensions could increase the deposition rate and inhibit cracks creation and propagation in the coatings. The corrosion resistant of the resulting samples were evaluated using potentiodynamic polarization method in simulated body fluid, and the GO-HY-HA coatings could effectively improve the anti-corrosion property of the Ti substrate.

  18. Biomimetic niche for neural stem cell differentiation using poly-L-lysine/hyaluronic acid multilayer films.

    PubMed

    Lee, I-Chi; Wu, Yu-Chieh; Cheng, En-Ming; Yang, Wen-Ting

    2015-05-01

    Polyelectrolyte multilayer films have been suggested as tunable substrates with flexible surface properties that can modulate cell behavior. However, these films' biological effects on neural stem/progenitor cells have rarely been studied. Herein, biomimetic multilayer films composed of hyaluronic acid and poly-L-lysine were chosen to mimic the native extracellular matrix niche of brain tissue and were evaluated for their inductive effects, without the addition of chemical factors. Because neural stem/progenitor cells are sensitive to substrate properties, it is important that this system provides control over the surface charge, and slight stiffness variations are also possible. Both of these factors affect neural stem/progenitor cell differentiation. The results showed that neural stem/progenitor cells were induced to differentiate on the poly-L-lysine/hyaluronic acid multilayer films with 0.5-4 alternating layers. In addition, the neurite outgrowth length was regulated by the surface charge of the terminal layer but did not increase with the layer number. In contrast, the quantity of differentiated neurons was enhanced slightly as the number of layers increased but was not affected by the surface charge of the terminal layer. In sum, material pairs in the form of native poly-L-lysine/hyaluronic acid films achieved important targets for neural regenerative medicine, including enhancement of the neurite outgrowth length, regulation of neuron differentiation, and the formation of a network. These extracellular matrix-mimetic poly-L-lysine/hyaluronic acid multilayer films may provide a versatile platform that could be useful for surface modification for applications in neural engineering.

  19. Treating atopic dermatitis: safety, efficacy, and patient acceptability of a ceramide hyaluronic acid emollient foam

    PubMed Central

    Pacha, Omar; Hebert, Adelaide A

    2012-01-01

    Advances in current understanding of the pathophysiology of atopic dermatitis have led to improved targeting of the structural deficiencies in atopic skin. Ceramide deficiency appears to be one of the major alterations in atopic dermatitis and the replenishment of this epidermal component through topically applied ceramide based emollients appears to be safe, well tolerated, and effective. Recently a ceramide hyaluronic acid foam has become commercially available and increasing evidence supports its safety and efficacy in patients who suffer from atopic dermatitis. PMID:22690129

  20. [Effect of the hyaluronic acid on tracheal healing. A canine experimental mode].

    PubMed

    Olmos-Zúñiga, J R; Santos-Cordero, J A; Jasso-Victoria, R; Sotres-Vega, A; Gaxiola-Gaxiola, M O; Mora-Fol, J R; Franco-Oropeza, J A; Santillan-Doherty, P

    2004-02-01

    Several drugs have been used to modulate of the tracheal healing process in order to prevent tracheal stenosis. Hyaluronic acid (HA) is a modulator of the fibrogenesis. In this work we evaluate the effect in order the application of hyaluronic acid has on tracheal healing, after cervical tracheoplasty in dogs. A cervical tracheal resection and tracheoplasty was performed in 12 dogs and they were treated following surgery as follows: Group I (n = 6) Topical application of normal saline solution (0.9%) on the anastomosis site. Group II Topical application of hyaluronic acid on the trachea anastomosed. The animals were evaluated clinical, radiological and tracheoscopically during 4 weeks and were submitted to euthanasia. Macroscopic and microscopic examinations of the tracheal anastomotic healing were evaluated. Biochemical collagen quantification by the Woessner method was performed to evaluate the collagen development at the anastomotic site. All the animals survived the surgical procedure and the study time. No animal presented differences in clinical evaluation. Radiological and endoscopical findings both two showed more development of the tracheal stenosis in-group than in group II. The tracheoscopy and macroscopic studies showed major inflammation and development of fibrotic tissue with a firm consistency in the healing of the group I than in group II. Microscopic examination in group I showed severe fibrosis and inflammatory reaction. The group II presented deposits of a thin and organized collagen fibers and minimal inflammatory reaction. Biochemical collagen concentration was larger in-group I, however significantly. We conclude that the hyaluronic acid applied after cervical tracheoplasty in dogs reduces postsurgical tracheal stenosis and inflammation, as well as improve the quality of the tracheal healing.

  1. Intra-articular injection of hyaluronic acid following arthroscopic partial meniscectomy of the knee.

    PubMed

    Thein, Rafael; Haviv, Barak; Kidron, Amos; Bronak, Shlomo

    2010-10-11

    The short-term recovery period post-arthroscopic meniscectomy is characterized by pain and impaired function most likely related to the irrigation of synovial fluid from the knee intraoperatively. Consequently, along with removal of harmful debris, the irrigation fluid dilutes the hyaluronic acid layer covering the joint tissues. Hyaluronic acid contributes to the homeostasis of the joint environment and is an important component of synovial fluid and cartilage matrix. Hence, the instillation of hyaluronic acid after the procedure may relieve symptoms. This prospective, single-blind, randomized, controlled study evaluated clinical outcome after hyaluronic acid injection to patients who underwent arthroscopic meniscectomy of the knee. Patients with ligamentous injuries or severe chondral damage were excluded. Fifty-six patients with a mean age of 34 years (range, 17-44 years) were injected with Viscoseal (TRB Chemedica International S.A., Geneva, Switzerland) or normal saline immediately post-arthroscopy and divided into the Viscoseal group or control group, respectively. Patients were evaluated for pain, swelling, and function at 1, 4, and 12 weeks postoperatively. Patients in the control group reported more pain at week 1, with a mean visual analog score (VAS) of 43, than did patients in the Viscoseal group, with a mean VAS of 28 (P=.006). At 4 weeks postoperatively, none of the Viscoseal patients had consumed analgesics, where 9 (of 28) in the control group reported acetaminophen intake (P=.039). No significant difference in knee function was found between groups. Intra-articular injection of Viscoseal after arthroscopic meniscectomy reduced pain in the short-term recovery period.

  2. Hyaluronic Acid Gel Re-Injection for Enophthalmos Correction in Silent Sinus Syndrome.

    PubMed

    Grusha, Yaroslav; Khovrin, Valerij; Stoyukhina, Alevtina; Sheptulin, Vladimir

    2015-01-01

    A 43-year-old female with residual enophthalmos following functional endoscopic surgery (FESS) due to silent sinus syndrome (SSS) was initially successfully treated with a 2-ml intraorbital injection of hyaluronic acid gel (HAG). The enophthalmos partially recurred 22 months after the injection. HAG was re-injected with good functional and cosmetic results. Functional (kinetic) computed tomography was performed to visualize HAG distribution in the orbit.

  3. CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice.

    PubMed

    Riehl, Terrence E; Santhanam, Srikanth; Foster, Lynne; Ciorba, Matthew; Stenson, William F

    2015-12-01

    Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3-8 wk of age to wild-type, CD44(-/-), and TLR4(-/-) mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5(+) stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5(+) reporter mice from postnatal day 7 to day 14 decreased Lgr5(+) cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5(+) stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4.

  4. Combined anticalcification treatment of bovine pericardium with decellularization and hyaluronic acid derivative.

    PubMed

    Zhu, Deyi; Jin, Liqiang; Wang, Xuemei; Xu, Li; Liu, Tianqi

    2014-01-01

    The objective of this work was to evaluate the effect of decellularization and hyaluronic acid derivative on the improvement of anticalcification of glutaraldehyde fixed bovine pericardium (GFBP) using a rat subcutaneous implantation model A cell extraction process was employed to remove the cells and cellular components from bovine pericardium (BP), leaving a framework of largely insoluble collagen. Then acellular BP was cross-linked by glutaraldehyde solution and treated with hyaluronic acid derivative (HA-ADH) which was obtained by coupling adipic dihydrazide (ADH) on-COOH of hyaluronic acid (HA). The results of in vivo calcification tests showed that the calcium content was decreased dramatically by decellularization alone (from 28.07 ± 18.87 to 2.44 ± 0.55 μg Ca/mg dry tissue after 8 weeks' implantation), and even less concentration was shown by the combination of HA derivative treatment and decellularization (GFaBP-HA group) (0.25 ± 0.08 μg Ca/mg dry tissue after 8 weeks' implantation). In addition, GFaBP-HA group not only presented a lower degree of calcification, but also showed lower ratios of Ca/P molar, which corresponded to amorphous calcium phosphates. The obtained results indicated that GFaBP-HA was a potential candidate for the manufacture of anticalcification bioprostheses.

  5. Determination of molecular weight of hyaluronic acid by near-infrared spectroscopy.

    PubMed

    Dong, Qin; Zang, Hengchang; Liu, Aihua; Yang, Guilan; Sun, Chunxiao; Sui, Linyan; Wang, Pei; Li, Lian

    2010-11-02

    This paper attempted the feasibility to determine the molecular weight of hyaluronic acid with near-infrared (NIR) diffuse reflectance spectroscopy. In this work, 46 experimental samples of hyaluronic acid powder were analyzed by partial least square (PLS) regression multivariate calibration method in the selected region of NIR spectra. The leave-one-out cross-validation method was used for the PLS model selection criterion. The accuracy of the final model was evaluated according to correlation coefficient of prediction set (Rp) and root mean square error of prediction set (RMSEP). The repeatability was verified through repeated measurement of spectra coupled with an appropriate chi-square test. Finally, the optimal calibration model was obtained with Rp=0.9814 and RMSEP=88.32 when using Savitzky-Golay first (SG-1st) derivative with 9 smoothing points spectral preprocessing method. The parameters above and repeatability of NIR spectroscopy obtained from chi-square test were both within the range of permissible error in factories. This study demonstrated that NIR spectroscopy was superior to conventional methods for the fast determination of molecular weight of hyaluronic acid.

  6. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer

    PubMed Central

    Jing, Lijia; shao, shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect. PMID:26722372

  7. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer.

    PubMed

    Jing, Lijia; Shao, Shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect.

  8. Human Growth Factor Cream and Hyaluronic Acid Serum in Conjunction with Micro Laser Peel

    PubMed Central

    Katz, Bruce E.; Cohen, Joel L.; Biron, Julie

    2010-01-01

    The present study investigated the use of a novel hyaluronic acid serum in combination with a cream comprising a mixture of human growth factors in conjunction with the micro laser peel procedure for skin rejuvenation. After preconditioning the face with the hyaluronic acid serum followed by the cream twice daily for one month, 15 female volunteers between 35 to 65 years of age with demonstrable facial wrinkling received a micro laser peel on the entire face using an erbium-doped yttrium aluminium garnet laser. Immediately following the laser procedure, the subjects applied the test products twice daily until the second laser peel one month later. Immediately following the second procedure, the subjects reapplied the test products for another month. In the large majority of subjects, erythema or edema, crusts or erosions, and transitory stinging or burning sensations after the micro laser peel were minimal or mild when the skin was treated with the serum followed by the cream. The micro laser peel in conjunction with the test products helped to significantly improve hyperpigmentation, wrinkles, and texture as compared to before treatment. This study with the micro laser peel device demonstrated that a novel hyaluronic acid serum combined with the human growth factor cream can be successfully used for skin rejuvenation in conjunction with light-to-medium invasive laser skin treatments. PMID:21203354

  9. Evaluation of cell interaction with polymeric biomaterials based on hyaluronic acid and chitosan.

    PubMed

    do Nascimento, Mônica Helena Monteiro; Ferreira, Mariselma; Malmonge, Sônia Maria; Lombello, Christiane Bertachini

    2017-05-01

    Tissue engineering involves the development of new materials or devices capable of specific interactions with biological tissues, searching the use of biocompatible materials as scaffolds for in vitro cell growth, and functional tissue development, that is subsequently implanted into patient. The aim of the current study was to evaluate the initial aspects of cell interaction with the polymeric biomaterials blends based on hyaluronic acid with chitosan. The hypothesis approach involves synthesis and analysis of swelling and thermal degradation (thermal gravimetric analysis) of the polymer blend; and Vero cell interaction with the biomaterial, through analysis of cytotoxicity, adhesion and cell morphology. The blend resulted in a biomaterial with a high swelling ratio that can allow nutrient distribution and absorption. The thermal gravimetric analysis results showed that the blend had two stages of degradation at temperatures very close to those observed for pure polymers, confirming that the physical mixing of hydrogels occurred, resulting in the presence of both hyaluronic acid and chitosan in the blend. The evaluation of indirect cytotoxicity showed that the blend was non cytotoxic for Vero cells, and the quantitative analysis performed with the MTT could verify a cell viability of 98%. The cells cultured on the blend showed adhesion, spreading and proliferation on this biomaterial, distinguished from the pattern of the control cells. These results showed that the blends produced from hyaluronic acid and chitosan hydrogels are promising for applications in tissue engineering, aiming at future cartilaginous tissue.

  10. Temperature and magnetic field responsive hyaluronic acid particles with tunable physical and chemical properties

    NASA Astrophysics Data System (ADS)

    Ekici, Sema; Ilgin, Pinar; Yilmaz, Selahattin; Aktas, Nahit; Sahiner, Nurettin

    2011-01-01

    We report the preparation and characterization of thiolated-temperature-responsive hyaluronic acid-cysteamine-N-isopropyl acrylamide (HA-CYs-NIPAm) particles and thiolated-magnetic-responsive hyaluronic acid (HA-Fe-CYs) particles. Linear hyaluronic acid (HA) crosslinked with divinyl sulfone as HA particles was prepared using a water-in-oil micro emulsion system which were then oxidized HA-O with NaIO4 to develop aldehyde groups on the particle surface. HA-O hydrogel particles were then reacted with cysteamine (CYs) which interacted with aldehydes on the HA surface to form HA particles with cysteamine (HA-CYs) functionality on the surface. HA-CYs particles were further exposed to radical polymerization with NIPAm to obtain temperature responsive HA-CYs-NIPAm hydrogel particles. To acquire magnetic field responsive HA composites, magnetic iron particles were included in HA to form HA-Fe during HA particle preparation. HA-Fe hydrogel particles were also chemically modified. The prepared HA-CYs-NIPAm demonstrated temperature dependent size variations and phase transition temperature. HA-CYs-NIPAm and HA-Fe-CYs particles can be used as drug delivery vehicles. Sulfamethoxazole (SMZ), an antibacterial drug, was used as a model drug for temperature-induced release studies from these particles.

  11. Intra-articular injections of hyaluronic acid (viscosupplementation) in the haemophilic knee.

    PubMed

    Rodriguez-Merchan, E Carlos

    2012-10-01

    Intra-articular injections (IAIs) of hyaluronic acid, also called viscosupplementation, can be used for the treatment of radiological haemophilic arthropathy of the knee, that is when mild-to-moderate degenerative changes can be visualized on plain radiographs. This article aims to define the efficacy of IAIs of hyaluronic acid in the treatment of radiological haemophilic arthropathy of the knee. A review of recent literature on the topic has been performed. The literature seems to support the use of hyaluronic acid in the treatment of knee osteoarthritis, because it diminishes pain and improves disability, generally within 1 week and for up to 3-12 months (but especially at the 5-13-week postinjection period). There are only five reports in the literature on the efficacy of knee viscosupplementation in haemophilia, all of them with a low level of evidence. The five studies dealing with viscosupplementation in haemophilia recommend it for haemophilic arthropathy of the knee as a way of delaying the need of operative treatment when noninvasive medical therapy (relative rest, oral anti-inflammatory drugs, oral analgesics and physical therapy) has failed. The short-lived improvement afforded by viscosupplementation does not, however, seem to warrant its use in haemophilic patients given the risks and the cost involved. Further trials are required to ascertain whether viscosupplementation should be indicated in painful radiological haemophilic arthropathy of the knee.

  12. Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review

    PubMed Central

    Prasetyo, Adri D; Prager, Welf; Rubin, Mark G; Moretti, Ernesto A; Nikolis, Andreas

    2016-01-01

    Background Cohesive monophasic polydensified fillers show unique viscoelastic properties and variable density of hyaluronic acid, allowing for a homogeneous tissue integration and distribution of the material. Objective The aim of this paper was to review the clinical data regarding the performance, tolerability, and safety of the Belotero® fillers for soft-tissue augmentation and rejuvenation. Methods A literature search was performed up until May 31, 2015 to identify all relevant articles on Belotero® fillers (Basic/Balance, Hydro, Soft, Intense, Volume) and equivalent products (Esthélis®, Mesolis®, Fortélis®, Modélis®). Results This comprehensive review included 26 papers. Findings from three randomized controlled trials showed a greater reduction in nasolabial fold severity with Belotero® Basic/Balance than with collagen (at 8, 12, 16, and 24 weeks, n=118) and Restylane® (at 4 weeks, n=40), and higher patient satisfaction with Belotero® Intense than with Perlane® (at 2 weeks, n=20). With Belotero® Basic/Balance, an improvement of at least 1 point on the severity scale can be expected in ~80% of patients 1–6 months after injection, with an effect still visible at 8–12 months. Positive findings were also reported with Belotero® Volume (no reduction in hyaluronic acid volume at 12 months, as demonstrated by magnetic resonance imaging), Soft (improvement in the esthetic outcomes when used in a sequential approach), and Hydro (improvement in skin appearance in all patients). The most common adverse effects were mild-to-moderate erythema, edema, and hematoma, most of which were temporary. There were no reports of Tyndall effect, nodules, granulomas, or tissue necrosis. Conclusion Clinical evidence indicates sustainable esthetic effects, good safety profile, and long-term tolerability of the Belotero® fillers, particularly Belotero® Basic/Balance and Intense. PMID:27660479

  13. Development of Injectable Hyaluronic Acid/Cellulose Nanocrystals Bionanocomposite Hydrogels for Tissue Engineering Applications.

    PubMed

    Domingues, Rui M A; Silva, Marta; Gershovich, Pavel; Betta, Sefano; Babo, Pedro; Caridade, Sofia G; Mano, João F; Motta, Antonella; Reis, Rui L; Gomes, Manuela E

    2015-08-19

    Injectable hyaluronic acid (HA)-based hydrogels compose a promising class of materials for tissue engineering and regenerative medicine applications. However, their limited mechanical properties restrict the potential range of application. In this study, cellulose nanocrystals (CNCs) were employed as nanofillers in a fully biobased strategy for the production of reinforced HA nanocomposite hydrogels. Herein we report the development of a new class of injectable hydrogels composed of adipic acid dihydrazide-modified HA (ADH-HA) and aldehyde-modified HA (a-HA) reinforced with varying contents of aldehyde-modified CNCs (a-CNCs). The obtained hydrogels were characterized in terms of internal morphology, mechanical properties, swelling, and degradation behavior in the presence of hyaluronidase. Our findings suggest that the incorporation of a-CNCs in the hydrogel resulted in a more organized and compact network structure and led to stiffer hydrogels (maximum storage modulus, E', of 152.4 kPa for 0.25 wt % a-CNCs content) with improvements of E' up to 135% in comparison to unfilled hydrogels. In general, increased amounts of a-CNCs led to lower equilibrium swelling ratios and higher resistance to degradation. The biological performance of the developed nanocomposites was assessed toward human adipose derived stem cells (hASCs). HA-CNCs nanocomposite hydrogels exhibited preferential cell supportive properties in in vitro culture conditions due to higher structural integrity and potential interaction of microenvironmental cues with CNC's sulfate groups. hASCs encapsulated in HA-CNCs hydrogels demonstrated the ability to spread within the volume of gels and exhibited pronounced proliferative activity. Together, these results demonstrate that the proposed strategy is a valuable toolbox for fine-tuning the structural, biomechanical, and biochemical properties of injectable HA hydrogels, expanding their potential range of application in the biomedical field.

  14. Influence of D-Penicillamine on the Viscosity of Hyaluronic Acid Solutions

    NASA Astrophysics Data System (ADS)

    Liang, Jing; Krause, Wendy E.; Colby, Ralph H.

    2006-03-01

    Polyelectrolyte hyaluronic acid (HA, hyaluronan) is an important component in synovial fluid. Its presence results in highly viscoelastic solutions with excellent lubricating and shock-absorbing properties. In comparison to healthy synovial fluid, diseased fluid has a reduced viscosity. In osteoarthritis this reduction in viscosity results from a decline in both the molecular weight and concentration of hyaluronic acid HA. Initial results indicate that D-penicillamine affects the rheology of bovine synovial fluid, a model synovial fluid solution, and its components, including HA. In order to understand how D-penicillamine modifies the viscosity of these solutions, the rheological properties of sodium hyaluronate (NaHA) in phosphate-buffered saline (PBS) with D-penicillamine were studied as function of time, D-penicillamine concentration (0 -- 0.01 M), and storage conditions. Penicillamine has a complex, time dependent effect on the viscosity of NaHA solutions---reducing the zero shear rate viscosity of a 3 mg/mL NaHA in PBS by ca. 40% after 44 days.

  15. Study on intralymphatic-targeted hyaluronic acid-modified nanoliposome: influence of formulation factors on the lymphatic targeting.

    PubMed

    Tiantian, Ye; Wenji, Zhang; Mingshuang, Sun; Rui, Yang; Shuangshuang, Song; Yuling, Mao; Jianhua, Yao; Xinggang, Yang; Shujun, Wang; Weisan, Pan

    2014-08-25

    In this study, hyaluronic acid-modified docetaxel-loaded liposomes were prepared to evaluate the lymphatic targeting after subcutaneous administration, and formulation factors affecting the lymphatic targeting were examined, including free hyaluronic acid, molecular weight, hyaluronic acid-density and particle diameter. The high molecular weight hyaluronic acid-modified docetaxel-loaded liposomes (HA-LPs) and low molecular weight hyaluronic acid-modified docetaxel-loaded liposomes (LMWHA-LPs) were prepared via electrostatic attraction. The physicochemical properties and in vitro drug release were evaluated. The lymphatic drainage and the lymph node uptake were investigated by pharmacokinetics and distribution recovery of docetaxel in lymph nodes, injection site and plasma. The lymphatic targeting ability of optimized Cy7-loaded LMWHA-LPs (LMWHA-LPs/Cy7) was evaluated by near-infrared fluorescence imaging technique. The result showed that HA-LPs and LMWHA-LPs with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Hyaluronic acid-modified liposome significantly increased the docetaxel recovery in lymph nodes, and displayed higher AUC(0-24h) and longer retention time compared to unmodified liposomes in vivo. In contrast, the presence of free hyaluronic acid hindered the lymphatic drainage and increased the plasma-drug concentration. Importantly, LMWHA-modification improved lymphatic drainage and lymph node uptake of liposomes compared with HA-modification. And Lymph node uptake of LMWHA-LPs depended mainly on LMWHA-density instead of particle size. The results of in vivo imaging showed that LMWHA-LPs/Cy7 significantly located in the lymphatic system. And both DTX-loaded and Cy7-loaded LMWHA-LPs had similar and stable lymphatic target level. Our investigation showed that LMWHA-LPs were a highly promising lymphatic targeting carrier for chemotherapy drugs and diagnostic fluorescence agents.

  16. Applications and Emerging Trends of Hyaluronic Acid in Tissue Engineering, as a Dermal Filler, and in Osteoarthritis Treatment

    PubMed Central

    Fakhari, Amir; Berkland, Cory

    2013-01-01

    Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine including scaffolding for tissue engineering, dermatological fillers, and viscosupplementation for osteoarthritis treatment. HA is available in most connective tissues in body fluids such as synovial fluid and the vitreous humor of the eye. HA is responsible for several structural properties of tissues as a component of extracellular matrix (ECM) and is involved in cellular signaling. Degradation of HA is a step-wise process that can occur via enzymatic or non-enzymatic reactions. A reduction in HA mass or molecular weight via degradation or slowing of synthesis affects physical and chemical properties such as tissue volume, viscosity, and elasticity. This review addresses the distribution, turnover, and tissue-specific properties of HA. This information is used as context for considering recent products and strategies for modifying the viscoelastic properties of HA in tissue engineering, as a dermal filler, and in osteoarthritis treatment. PMID:23507088

  17. Early Experience with Hyaluronic Acid Instillation to Assist with Visual Internal Urethrotomy for Urethral Stricture

    PubMed Central

    Kim, Hak Min; Kang, Dong Il; Shim, Bong Suk

    2010-01-01

    Purpose The clinical usefulness of hyaluronic acid (HA) instillation during visual internal urethrotomy (VIU) for decreasing the incidence of recurrent urethral stricture was assessed. Materials and Methods Twenty-eight patients were treated by VIU with HA instillation between May 2007 and June 2009. After insertion of a Foley catheter following urethrotomy, HA was instilled via an 18-gauge tube catheter between the urethral lumen and Foley catheter. Seventeen cases were analyzed retrospectively 12 months postoperatively. We evaluated the success rate of this procedure by comparing retrograde urethrography (RGU) results, maximum flow rates, and postvoid residual urine volumes preoperatively and 3 and 12 months postoperatively. Success was defined as either a maximum flow rate of at least 15 ml/s or no visible urethral stricture on RGU at 12 months postoperatively. Results Total success rates were 76.5% (13/17) and 52.9% (9/17) at 3 and 12 months postoperatively, respectively. By etiology, success rates at 3 and 12 months postoperatively, respectively, were 66.7% and 33.3% for inflammation, 66.7% and 50.0% for trauma, and 83.3% and 66.7% for unknown causes. Success rates were 63.6% for strictures less than 10 mm in length and 33.3% for strictures of 10 mm or more in length at 12 months postoperatively. Success rates were 61.5% for single strictures and 25% for multiple strictures at 12 months postoperatively. Conclusions The success rate of VIU with HA instillation was not better than that observed in the literature for conventional VIU. PMID:21221206

  18. Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil.

    PubMed

    Yadav, Awesh K; Agarwal, Abhinav; Rai, Gopal; Mishra, Pradeep; Jain, Sanyog; Mishra, Anil K; Agrawal, Himanshu; Agrawal, Govind P

    2010-11-01

    The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.

  19. A novel DTPA cross-linking of hyaluronic acid and metal complexation thereof.

    PubMed

    Buffa, Radovan; Běťák, Jiří; Kettou, Sofiane; Hermannová, Martina; Pospíšilová, Lucie; Velebný, Vladimír

    2011-09-27

    Macromolecular conjugates of a natural polysaccharide, hyaluronic acid, with diethylenetriaminepentaacetic acid (DTPA)-metal complexes were synthesized and characterized by FTIR, NMR, SEC-MALLS and ICP analysis. Several parameters of the cross-linking reaction as molecular weight of starting HA, temperature, equivalent of DTPA bis-anhydride, concentration of HA, presence of transacylation catalyst DMAP and reaction time were studied. The mechanism for the reaction was suggested and relationship between the molecular weight assigned by SEC-MALLS, reaction parameters and rheological properties of the final cross-linked products were investigated.

  20. Electrophoretic deposition of hyaluronic acid and composite films for biomedical applications

    NASA Astrophysics Data System (ADS)

    Ma, R.; Li, Y.; Zhitomirsky, I.

    2010-06-01

    Hyaluronic acid (HYH) is a natural biopolymer, which has tremendous potential for various biomedical applications. Electrophoretic deposition (EPD) methods have been developed for the fabrication of HYH films and composites. New methods for the immobilization of drugs and proteins have been utilized for the fabrication of organic composites. Electrophoretic deposition enabled the fabrication of organic-inorganic composites containing bioceramics and bioglass in the HYH matrix. It was shown that the deposition yield, microstructure, and composition of the films can be controlled. Potential applications of EPD for the surface modification of biomedical implants and fabrication of biosensors are highlighted.

  1. Length Scale Dependence of the Dynamic Properties of Hyaluronic Acid Solutions in the Presence of Salt

    SciTech Connect

    Horkay, Ferenc; Falus, Peter; Hecht, Anne-Marie; Geissler, Erik

    2010-12-07

    In solutions of the charged semirigid biopolymer hyaluronic acid in salt-free conditions, the diffusion coefficient D{sub NSE} measured at high transfer momentum q by neutron spin echo is more than an order of magnitude smaller than that determined by dynamic light scattering, D{sub DLS}. This behavior contrasts with neutral polymer solutions. With increasing salt content, D{sub DLS} approaches D{sub NSE}, which is independent of ionic strength. Contrary to theoretical expectation, the ion-polymer coupling, which dominates the low q dynamics of polyelectrolyte solutions, already breaks down at distance scales greater than the Debye-Hueckel length.

  2. Intra-articular hyaluronic acid in the treatment of haemophilic chronic arthropathy.

    PubMed

    Fernández-Palazzi, F; Viso, R; Boadas, A; Ruiz-Sáez, A; Caviglia, H; De Bosch, N Blumenfeld

    2002-05-01

    We report our preliminary experience with the use of hyaluronic acid (Synvisc) in 29 joints from 25 different haemophilic patients (17 knees, six shoulders, four ankles, one elbow and one hip). All the joints were grade III of our classification, characterized by synovial thickening, axial deformities and muscle atrophy (chronic arthropathy). In view of the very satisfactory results obtained with this procedure, we have substituted Synvisc for the previous use of intra-articular long-standing corticosteroids that we had been used for some years. This method is theoretically more physiological and does not destroy the joint cartilage further, as corticosteroids can.

  3. [Use of hyaluronidase to correct hyaluronic acid injections in aesthetic medicine].

    PubMed

    Lacoste, C; Hersant, B; Bosc, R; Noel, W; Meningaud, J P

    2016-04-01

    Hyaluronic acid (HA) is the most commonly used filler in aesthetic medicine. However, overcorrections are frequent even with experienced practitioner. Hyaluronidase is an enzyme that hydrolyzes HA. Hyaluronidase has been recently proposed to correct unsatisfactory results of HA injections in aesthetic medicine (overcorrection, asymmetry, Tyndall effect) and to treat immediate complications such as arterial or venous thrombosis. The objective of this technical note was to summarize the literature data regarding the efficacy, safety and technique of use of hyaluronidase. Hyaluronidase may be responsible for allergies. The practitioner should take this risk and the possible drug interactions into account before using this antidote in order to weigh up the risk/benefit ratio.

  4. [Hyaluronic acid: a new trend to cure skin injuries an observational study].

    PubMed

    Rueda Lópex, Justo; Segovia Gómez, Teresa; Guerrero Palmero, Alberto; Bermejo Martínez, Mariano; Muñoz Bueno, Ana Maria

    2005-06-01

    The authors made an observational study to evaluate the efficiency of Jaloplast (hyaluronic acid AH) as treatment for skin injuries having different etiologies. The authors highlight its results regarding cicatrisation (69%) and the improvement of lesions (15.38%). Moreover 80% of lesions have cicatrized in a time less than 11 weeks, without showing any adverse effects nor secondary effects. From these observations, the authors deduce the importance of this molecule formed by glucosamine glycane (hyalyuronate) at the organic level in general and specifically in the process of cicatrisation.

  5. Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.

    PubMed

    Zhang, Pan; Yang, Hui; Wang, Guojun; Tong, Weijun; Gao, Changyou

    2016-06-01

    The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization.

  6. Effect of gamma irradiation on hyaluronic acid and dipalmitoylphosphatidylcholine (DPPC) interaction

    NASA Astrophysics Data System (ADS)

    Ahmad, Ainee Fatimah; Mohd, Hur Munawar Kabir; bin Ayob, Muhammad Taqiyuddin Mawardi; Rosli, Nur Ratasha Alia Md; Mohamed, Faizal; Radiman, Shahidan; Rahman, Irman Abdul

    2014-09-01

    DPPC lipids are the major component constituting the biological membrane, and their importances in various physiological functions are well documented. Hyaluronic acid (HA) in the synovial joint fluid functions as a lubricant, shock absorber and a nutrient carrier. Gamma irradiation has also been found to be effective in depolymerizing and cleaving molecular chains related to free radicals, thus extends with changes in chemical composition as well as its physiological functions. This research are conducted to investigate the hyaluronic acid (HA) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) interaction in form of vesicles and its effect to gamma radiation. The size of DPPC vesicles formed via gentle hydration method is between 100 to 200 nm in diameter. HA (0.1, 0.5 and 1.0 mg/ml) was added into the vesicles and characterized by using TEM to determine vesicle size distributions, fusion and rupture of DPPC structure. The results demonstrated that the size of the vesicles approximately between 200 to 300 nm which caused by vesicles fusion with HA and formed even larger vesicles. After being irradiated by 0 to 200 Gy, the size of vesicles decreased as HA was degraded. To elucidate the mechanism of these effects, FTIR spectra were carried out and have shown that at absorption bands at 1700-1750 cm-1 due to formation of carboxylic acid and leads to alteration of HA structure.

  7. Effect of gamma irradiation on hyaluronic acid and dipalmitoylphosphatidylcholine (DPPC) interaction

    SciTech Connect

    Ahmad, Ainee Fatimah; Mohd, Hur Munawar Kabir; Taqiyuddin Mawardi bin Ayob, Muhammad; Rosli, Nur Ratasha Alia Md; Mohamed, Faizal; Radiman, Shahidan; Rahman, Irman Abdul

    2014-09-03

    DPPC lipids are the major component constituting the biological membrane, and their importances in various physiological functions are well documented. Hyaluronic acid (HA) in the synovial joint fluid functions as a lubricant, shock absorber and a nutrient carrier. Gamma irradiation has also been found to be effective in depolymerizing and cleaving molecular chains related to free radicals, thus extends with changes in chemical composition as well as its physiological functions. This research are conducted to investigate the hyaluronic acid (HA) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) interaction in form of vesicles and its effect to gamma radiation. The size of DPPC vesicles formed via gentle hydration method is between 100 to 200 nm in diameter. HA (0.1, 0.5 and 1.0 mg/ml) was added into the vesicles and characterized by using TEM to determine vesicle size distributions, fusion and rupture of DPPC structure. The results demonstrated that the size of the vesicles approximately between 200 to 300 nm which caused by vesicles fusion with HA and formed even larger vesicles. After being irradiated by 0 to 200 Gy, the size of vesicles decreased as HA was degraded. To elucidate the mechanism of these effects, FTIR spectra were carried out and have shown that at absorption bands at 1700–1750 cm{sup −1} due to formation of carboxylic acid and leads to alteration of HA structure.

  8. Evaluation and biological characterization of bilayer gelatin/chondroitin-6-sulphate/hyaluronic acid membrane.

    PubMed

    Wang, Tzu-Wei; Sun, Jui-Sheng; Wu, Hsi-Chin; Huang, Yi-Chau; Lin, Feng-Huei

    2007-08-01

    A biodegradable polymer scaffold was developed using gelatin, chondroitin-6-sulphate, and hyaluronic acid in the form of bilayer network. The bilayer porous structure of gelatin-chondroitin-6-sulphate-hyaluronic acid (G-C6S-HA) membrane was fabricated using different freezing temperatures followed by lyophilization. 1-Ethyl-3(3-dimethylaminopropyl) carbodiimide was used as crosslinking agent to improve the biological stability of the scaffold. The morphology, physical-chemical properties, and biocompatibility of bilayer G-C6S-HA membrane were evaluated in this study. The functional groups change in crosslinked G-C6S-HA scaffold was characterized by fourier transform infrared spectroscopy. The retention of glycosaminoglycan contents and matrix degradation rate were also examined by p-dimethylamino benzaldehyde and 2,4,6-trinitrobenzene sulphonic acid, respectively. Water absorption capacity was carried out to study G-C6S-HA membrane water containing characteristics. The morphology of the bilayer G-C6S-HA membrane was investigated under scanning electron microscope and light microscopy. In vitro biocompatibility was conducted with MTT test, LDH assay, as well as histological analysis. The results showed that the morphology of bilayer G-C6S-HA membrane was well reserved. The physical-chemical properties were also adequate. With good biocompatibility, this bilayer G-C6S-HA membrane would be suitable as a matrix in the application of tissue engineering.

  9. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models

    PubMed Central

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model. PMID:27822014

  10. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models.

    PubMed

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model.

  11. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.

    PubMed

    Kushchayev, Sergiy V; Giers, Morgan B; Hom Eng, Doris; Martirosyan, Nikolay L; Eschbacher, Jennifer M; Mortazavi, Martin M; Theodore, Nicholas; Panitch, Alyssa; Preul, Mark C

    2016-07-01

    OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel-treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel-treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel-treated group. There was a decreased presence of inflammatory cells in the HA hydrogel-treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a

  12. Mechanical Characterization of a Dynamic and Tunable Methacrylated Hyaluronic Acid Hydrogel

    PubMed Central

    Ondeck, Matthew G.; Engler, Adam J.

    2016-01-01

    Hyaluronic acid (HA) is a commonly used natural polymer for cell scaffolding. Modification by methacrylate allows it to be polymerized by free radicals via addition of an initiator, e.g., light-sensitive Irgacure, to form a methacrylated hyaluronic acid (MeHA) hydrogel. Light-activated crosslinking can be used to control the degree of polymerization, and sequential polymerization steps allow cells plated onto or in the hydrogel to initially feel a soft and then a stiff matrix. Here, the elastic modulus of MeHA hydrogels was systematically analyzed by atomic force microscopy (AFM) for a number of variables including duration of UV exposure, monomer concentration, and methacrylate functionalization. To determine how cells would respond to a specific two-step polymerization, NIH 3T3 fibroblasts were cultured on the stiffening MeHA hydrogels and found to reorganize their cytoskeleton and spread area upon hydrogel stiffening, consistent with cells originally cultured on substrates of the final elastic modulus. PMID:26746491

  13. Hyaluronic Acid Conjugated Magnetic Prussian Blue@Quantum Dot Nanoparticles for Cancer Theranostics

    PubMed Central

    Yang, Yongbo; Jing, Lijia; Li, Xiaoda; Lin, Li; Yue, Xiuli; Dai, Zhifei

    2017-01-01

    A multifunctional nanotheranostic agent was developed by conjugating both hyaluronic acid and bovine serum albumin coated CuInS2-ZnS quantum dots onto the surface of magnetic Prussian blue nanoparticles. The obtained nanoagent could serve as an efficient contrast agent to simultaneously enhance near infrared (NIR) fluorescence and magnetic resonance (MR) imaging greatly. The coexistence of magnetic core and CD44 ligand hyaluronic acid was found to largely improve the specific uptake of the nanoagent by CD44 overexpressed HeLa cells upon applying an external magnetic field. Both NIR fluorescence and MR imaging in vivo proved high accumulation of the nanoagent at tumor site due to its excellent CD44 receptor/magnetic dual targeting capability. After intravenous injection of the nanoagent and treatment of external magnetic field, the tumor in nude mice was efficiently ablated upon NIR laser irradiation and the tumor growth inhibition was more than 89.95%. Such nanotheranostic agent is of crucial importance for accurately identifying the size and location of the tumor before therapy, monitoring the photothermal treatment procedure in real-time during therapy, assessing the effectiveness after therapy. PMID:28255343

  14. Hyaluronic Acid-Chitosan Nanoparticles to Deliver Gd-DTPA for MR Cancer Imaging

    PubMed Central

    Zhang, Li; Liu, Tingxian; Xiao, Yanan; Yu, Dexin; Zhang, Na

    2015-01-01

    Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially at the early stage of tumors. Recently, polyionic nanocomplexes (PICs), which are composed of polyanions and opposite polycations, have been demonstrated to be a promising strategy for biomedical applications. In this work, chitosan-hyaluronic acid nanoparticles (GCHN) were developed to deliver Gd-DTPA as MRI contrast agents for tumor diagnosis. The Gd-labeled conjugates (CS-DTPA-Gd) were successfully synthesized by carbodiimide reaction, and then GCHN were prepared by ionic gelation using the obtained CS-DTPA-Gd and hyaluronic acid. The morphology of GCHN was spherical or ellipsoidal, which is observed by transmission electronic microscopy (TEM). The mean particle size and zeta potential of GCHN were 213.8 ± 2.6 nm and 19.92 ± 1.69 mV, respectively. The significant enhancement of signal intensity induced by GCHN was observed both in vitro and in vivo. Also, compared with Magnevist, GCHN was witnessed for a prolonged imaging time in the B16 tumor-bearing mice model. Furthermore, GCHN were verified as below toxic both in vitro and in vivo. These results indicated that GCHN could potentially be an alternative to current MRI contrast agents for tumor diagnosis.

  15. Glutathione Responsive Hyaluronic Acid Nanocapsules Obtained by Bioorthogonal Interfacial "Click" Reaction.

    PubMed

    Baier, Grit; Fichter, Michael; Kreyes, Andreas; Klein, Katja; Mailänder, Volker; Gehring, Stephan; Landfester, Katharina

    2016-01-11

    Azide-functionalized hyaluronic acid and disulfide dialkyne have been used for "click" reaction polymerization at the miniemulsion droplets interface leading to glutathione responsive nanocapsules (NCs). Inverse miniemulsion polymerization was chosen, due to its excellent performance properties, for example, tuning of size and size distribution, shell thickness/density, and high pay loading efficiency. The obtained size, size distribution, and encapsulation efficiency were checked via fluorescent spectroscopy, and the tripeptide glutathione was used to release an encapsulated fluorescent dye after cleavage of the nanocapsules shell. To show the glutathione-mediated intracellular cleavage of disulfide-containing NC shells, CellTracker was encapsulated into the nanocapsules. The cellular uptake in dendritic cells and the cleavage of the nanocapsules in the cells were studied using confocal laser scanning microscopy. Because of the mild reaction conditions used during the interfacial polymerization and the excellent cleavage properties, we believe that the synthesis of glutathione responsive hyaluronic acid NCs reported herein are of high interest for the encapsulation and release of sensitive compounds at high yields.

  16. Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone suppresses SEB-induced lung inflammation.

    PubMed

    McKallip, Robert J; Hagele, Harriet F; Uchakina, Olga N

    2013-10-17

    Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

  17. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

    PubMed Central

    McKallip, Robert J.; Hagele, Harriet F.; Uchakina, Olga N.

    2013-01-01

    Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB. PMID:24141285

  18. A Hyaluronic Acid-Rich Node and Duct System in Which Pluripotent Adult Stem Cells Circulate.

    PubMed

    Rai, Rajani; Chandra, Vishal; Kwon, Byoung S

    2015-10-01

    Regenerative medicine is in demand of adult pluripotent stem cells (PSCs). The "Bonghan System (BHS)" was discovered and suggested to contain cells with regenerative capacity in the early 1960s. It had been ignored for a long time due to the lack of sufficient details of experiments, but about 37 years after the initial report, the BHS was rediscovered and named as the "primo vascular system." Recently, we have discovered a similar structure, which contained a high level of hyaluronic acid, and hence, named the structure as hyaluronic acid-rich node and duct system (HAR-NDS). Here we discuss the HAR-NDS concept starting from the discovery of BHS, and findings pointing to its importance in regenerative medicine. This HAR-NDS contained adult PSCs, called node and duct stem cells (NDSCs), which appeared to circulate in it. We describe the evidence that NDSCs can differentiate into hemangioblasts that further produced differentiated blood cells. The NDSCs had a potential to differentiate into neuronal cells and hepatocytes; thus, NDSCs had a capability to become cells from all three germ layers. This system appears to be a promising alternative source of adult stem cells that can be easily delivered to their target tissues and participate in tissue regeneration.

  19. Posterior Ciliary Artery Occlusion Caused by Hyaluronic Acid Injections Into the Forehead: A Case Report.

    PubMed

    Hu, Xiu Zhuo; Hu, Jun Yan; Wu, Peng Sen; Yu, Sheng Bo; Kikkawa, Don O; Lu, Wei

    2016-03-01

    Although cosmetic facial soft tissue fillers are generally safe and effective, improper injections can lead to devastating and irreversible consequences. We represent the first known case of posterior ciliary artery occlusion caused by hyaluronic acid. A 41-year-old female presented with right visual loss 7 hours after receiving cosmetic hyaluronic acid injections into her forehead. Examination revealed no light perception in the right eye and multiple dark ischemic area of injection over the forehead and nose. The right fundus revealed a pink retina with optic nerve edema. Fluorescein angiogram showed several filling defects in the choroidal circulation and late hyperfluorescence in the choroid. A right posterior ciliary artery occlusion and embolic occlusion of facial artery braches was diagnosed. With hyaluronidase injection, hyperbaric oxygen therapy, oral aspirin, oral acetazolamide and dexamethasone venotransfuse treatment, the patient's forehead and nasal skin improved and vision recovered to hand movements. With proper technique, vascular occlusion is rare following facial filler injection. Vision consequences can be severe if filler emboli enter the ocular circulation. Physicians should be aware of this potential side effect, recognize its presentation, and be knowledgeable of effective management.

  20. Injection Rhinoplasty with Hyaluronic Acid and Calcium Hydroxyapatite: A Retrospective Survey Investigating Outcome and Complication Rates.

    PubMed

    Schuster, Bernd

    2015-06-01

    Injection rhinoplasty offers an attractive, reversible alternative to surgery. Here we assessed outcome, longevity of benefits, adverse effects, and patient assessment of injection rhinoplasty, using degradable synthetic fillers. Forty-six patients who underwent injection rhinoplasty using degradable fillers over the past 3 years were assessed (calcium hydroxyapatite: 26 patients, hyaluronic acid: 20 patients). Comparison of pre- and postoperative images indicated realistically achievable treatment results. Patient satisfaction was assessed using a 5-point questionnaire at 3 weeks and 9 months posttreatment. Forty-six patients (88 areas) were treated. At 3 weeks posttreatment, 85% of patients were satisfied with treatment results. At 9 months or later posttreatment, 87% of patients were very/completely satisfied with treatment results, regardless of filler used. Treatment longevity varied between 6 and 30 months (mean: 13.5 months). Positive evaluation was mainly due to accurate prediction of achievable results to meet patient expectations. There were one moderate and two severe complications, all following calcium hydroxyapatite treatment. Two resolved completely following treatment and one patient was lost to follow-up. This resulted in subsequent exclusive use of hyaluronic acid filler. Injectable biodegradable fillers are effective for correction of minor nasal deformities or irregularities. Attention must be given to injection technique and adverse effect management.

  1. Hyaluronic acid membrane for reducing adhesion formation and reformation in the rat uterine horn.

    PubMed

    Yarali, H; Zahradka, B F; Gomel, V

    1994-09-01

    The efficacy of hyaluronic acid (HA) membrane in preventing or reducing intraperitoneal adhesion formation and reformation was evaluated in the rat uterine horn. Forty-seven Wistar rats were employed. Following a measured laser injury on the right uterine horn of each rat, HA membrane was applied to cover the site of injury in 20 (HA membrane group). No membrane was applied in another 20 (control group). The type and extent of adhesions were assessed at relaparotomy. Following microsurgical adhesiolysis at second-look laparotomy, the same animals were randomized to the HA membrane and control groups. The type and extent of adhesion reformation were evaluated at third-look laparotomy. Following a similar injury on the right uterine horn in another seven rats, HA membrane was applied on both uterine horns. A repeat laparotomy was performed three hours later to assess the status of the membrane. The type and extent of adhesion formation and reformation were comparable between the HA membrane and control groups. The HA membrane did not remain on the uterine horn and gelled rapidly. Hyaluronic acid membrane was ineffective in reducing adhesion formation and reformation in the rat uterine horn.

  2. A Novel Cross-Linked Hyaluronic Acid Porous Scaffold for Cartilage Repair

    PubMed Central

    Bauer, Christoph; Berger, Manuela; Baumgartner, Renate R.; Höller, Sonja; Zwickl, Hannes; Niculescu-Morzsa, Eugenia; Halbwirth, Florian; Nehrer, Stefan

    2015-01-01

    Purpose An important feature of biomaterials used in cartilage regeneration is their influence on the establishment and stabilization of a chondrocytic phenotype of embedded cells. The purpose of this study was to examine the effects of a porous 3-dimensional scaffold made of cross-linked hyaluronic acid on the expression and synthesis performance of human articular chondrocytes. Materials and Methods Osteoarthritic chondrocytes from 5 patients with a mean age of 74 years were passaged twice and cultured within the cross-linked hyaluronic acid scaffolds for 2 weeks. Analyses were performed at 3 different time points. For estimation of cell content within the scaffold, DNA-content (CyQuant cell proliferation assay) was determined. The expression of chondrocyte-specific genes by embedded cells as well as the total amount of sulfated glycosaminoglycans produced during the culture period was analyzed in order to characterize the synthesis performance and differentiation status of the cells. Results Cells showed a homogenous distribution within the scaffold. DNA quantification revealed a reduction of the cell number. This might be attributed to loss of cells from the scaffold during media exchange connected with a stop in cell proliferation. Indeed, the expression of cartilage-specific genes and the production of sulfated glycosaminoglycans were increased and the differentiation index was clearly improved. Conclusions These results suggest that the attachment of osteoarthritic P2 chondrocytes to the investigated material enhanced the chondrogenic phenotype as well as promoted the retention. PMID:27375842

  3. Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

    PubMed Central

    Lee, Jae Young; Schmidt, Christine E.

    2010-01-01

    Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors. PMID:20558330

  4. The role of hyaluronic acid in patients affected by glenohumeral osteoarthritis.

    PubMed

    Di Giacomo, G; De Gasperis, N

    2015-01-01

    Persistent shoulder pain is a highly prevalent problem, due to different pathologies, that is frequently associated with limited range of motion and decreased function. The correct diagnosis can lead to the best treatment for each pathology. In this study we tried to understand what could be the role of hyaluronic acid and its effective benefit in patients affected by mild-to-moderate glenohumeral osteoarthritis. From January 2013 to June 2014, we prospectively followed-up 61 consecutive patients with shoulder osteoarthritis degrees I, II, and III. We divided the patients into 2 homogeneous groups: 31 patients in the first group treated with 5 intra-articular injections of Hyalgan 20mg/2ml and a specific physiotherapy program, and 30 patients in the second group treated only with physical therapy. The mean follow-up examination was carried out 5.2 months after the beginning of the therapy for both groups. The statistical analysis revealed a significant difference (P less than 0.05) between the two groups in terms of pain reduction and improvement in the activities of daily living. The present study demonstrates the greater and long-lasting efficacy of a five-injection treatment with hyaluronic acid (Hyalgan 20mg/2ml) combined with a physical therapy program in comparison with physical therapy only in patients affected by glenohumeral osteoarthritis degree I, II or III.

  5. Diclofenac in hyaluronic acid gel: an alternative treatment for actinic cheilitis

    PubMed Central

    LIMA, Giana da Silveira; da SILVA, Gabriela Ferrari; GOMES, Ana Paula Neutzling; de ARAÚJO, Lenita Maria Aver; SALUM, Fernanda Gonçalves

    2010-01-01

    Objective Actinic cheilitis (AC) is a precancerous lesion of the lip vermillion caused by prolonged exposure to ultraviolet light. The aim of this study was to evaluate the effect of 3% diclofenac in 2.5% hyaluronic acid gel in the treatment of AC. Methods Thirty-four patients with chronic AC were treated twice a day with topical diclofenac during a period of 30 to 180 days. The individuals were followed up every 15 days by means of clinical examination and digital photographic documentation. Results Of the 27 patients that completed the study, 12 (44%) showed complete remission of the whitish plaques and exfoliative areas, and 15 (56%) had partial remission of the clinical picture of cheilitis. The latter group was submitted to excision of the leukoplakic areas which diagnosis varied from mild to moderate epithelial dysplasia. Conclusion The results suggest a promising role for diclofenac in hyaluronic acid gel in the treatment of AC. This treatment has the advantages of not being invasive and showing few side effects. PMID:21085813

  6. Contact Sensitizers Induce Skin Inflammation via ROS Production and Hyaluronic Acid Degradation

    PubMed Central

    Esser, Philipp R.; Wölfle, Ute; Dürr, Christoph; von Loewenich, Friederike D.; Schempp, Christoph M.; Freudenberg, Marina A.; Jakob, Thilo; Martin, Stefan F.

    2012-01-01

    Background Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed the role of contact sensitizer induced ROS production and concomitant changes in hyaluronic acid metabolism on CHS responses. Methodology/Principal Findings We analyzed in vitro and in vivo ROS production using fluorescent ROS detection reagents. HA fragmentation was determined by gel electrophoresis. The influence of blocking ROS production and HA degradation by antioxidants, hyaluronidase-inhibitor or p38 MAPK inhibitor was analyzed in the murine CHS model. Here, we demonstrate that organic contact sensitizers induce production of reactive oxygen species (ROS) and a concomitant breakdown of the extracellular matrix (ECM) component hyaluronic acid (HA) to pro-inflammatory low molecular weight fragments in the skin. Importantly, inhibition of either ROS-mediated or enzymatic HA breakdown prevents sensitization as well as elicitation of CHS. Conclusions/Significance These data identify an indirect mechanism of contact sensitizer induced innate inflammatory signaling involving the breakdown of the ECM and generation of endogenous danger signals. Our findings suggest a beneficial role for anti-oxidants and hyaluronidase inhibitors in prevention and treatment of ACD. PMID:22848468

  7. Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

    PubMed

    McKallip, Robert J; Ban, Hao; Uchakina, Olga N

    2015-01-01

    Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

  8. Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

    PubMed Central

    Ziganshina, M. M.; Pavlovich, S. V.; Bovin, N. V.; Sukhikh, G. T.

    2016-01-01

    Preeclampsia (PE) is a multisystem pathologic state that clinically manifests itself after the 20th week of pregnancy. It is characterized by high maternal and perinatal morbidity and mortality. According to modern concepts, the impairment of trophoblast invasion into maternal spiral arteries, leading to the development of ischemia in placenta, is considered to be the major pathogenetic factor of PE development. Ischemic lesions initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction, which is the main cause of the multiple organ failure in PE. Some data has appear indicating the importance of a glycans-forming endothelial glycocalyx and extracellular matrix (ECM) for placenta morphogenesis, as well as their role in the regulation of vascular permeability and vascular tone in hypertension disorders and, in particular, PE. Since intact glycocalyx and ECM are considered to be the major factors that maintain the physiological vascular tone and adequate intercellular interactions, their value in PE pathogenesis is underestimated. This review is focused on hyaluronic acid (HA) as the key glycan providing the organization and stabilization of the ECM and glycocalyx, its distribution in tissues in the case of presence or absence of placental pathology, as well as on the regulatory function of hyaluronic acids of various molecular weights in different physiological and pathophysiological processes. The summarized data will provide a better understanding of the PE pathogenesis, with the main focus on glycopathology. PMID:27795844

  9. Hyaluronic acid injections for knee osteoarthritis. Systematic review of the literature.

    PubMed Central

    Aggarwal, Anita; Sempowski, Ian P.

    2004-01-01

    OBJECTIVE: To determine whether viscosupplementation with intra-articular hyaluronic acid (HA) injections improves pain and function in patients with osteoarthritis (OA) in their knees. DATA SOURCES: We searched MEDLINE, Pre-MEDLINE, and Cochrane databases using the MeSH headings and key words osteoarthritis (knee) and hyaluronic acid. STUDY SELECTION: English-language case series and randomized controlled trials (RCTs) were selected. Studies with biologic, histologic, or arthroscopic outcomes were excluded. SYNTHESIS: Five case series and 13 RCTs were critically appraised. Data from three case series and three RCTs using injections of high-molecular-weight HA (Synvisc) demonstrated significant improvement in pain, activity levels, and function. The beneficial effect started as early as 12 weeks. Studies using low-molecular-weight HA had conflicting results. CONCLUSION: Viscosupplementation with high-molecular-weight HA is an effective treatment for patients with knee OA who have ongoing pain or are unable to tolerate conservative treatment or joint replacement. Viscosupplementation appears to have a slower onset of action than intra-articular steroids, but the effect seems to last longer. PMID:15000336

  10. Global Aesthetics Consensus: Avoidance and Management of Complications from Hyaluronic Acid Fillers—Evidence- and Opinion-Based Review and Consensus Recommendations

    PubMed Central

    Liew, Steven; Sundaram, Hema; De Boulle, Koenraad L.; Goodman, Greg J.; Monheit, Gary; Wu, Yan; Trindade de Almeida, Ada R.; Swift, Arthur; Vieira Braz, André

    2016-01-01

    Background: Although the safety profile of hyaluronic acid fillers is favorable, adverse reactions can occur. Clinicians and patients can benefit from ongoing guidance on adverse reactions to hyaluronic acid fillers and their management. Methods: A multinational, multidisciplinary group of experts in cosmetic medicine convened the Global Aesthetics Consensus Group to review the properties and clinical uses of Hylacross and Vycross hyaluronic acid products and develop updated consensus recommendations for early and late complications associated with hyaluronic acid fillers. Results: The consensus panel provided specific recommendations focusing on early and late complications of hyaluronic acid fillers and their management. The impact of patient-, product-, and technique-related factors on such reactions was described. Most of these were noted to be mild and transient. Serious adverse events are rare. Early adverse reactions to hyaluronic acid fillers include vascular infarction and compromise; inflammatory reactions; injection-related events; and inappropriate placement of filler material. Among late reactions are nodules, granulomas, and skin discoloration. Most adverse events can be avoided with proper planning and technique. Detailed understanding of facial anatomy, proper patient and product selection, and appropriate technique can further reduce the risks. Should adverse reactions occur, the clinician must be prepared and have tools available for effective treatment. Conclusions: Adverse reactions with hyaluronic acid fillers are uncommon. Clinicians should take steps to further reduce the risk and be prepared to treat any complications that arise. PMID:27219265

  11. Efficacy of hyaluronic acid or steroid injections for the treatment of a rat model of rotator cuff injury.

    PubMed

    Yamaguchi, Takeshi; Ochiai, Nobuyasu; Sasaki, Yu; Kijima, Takehiro; Hashimoto, Eiko; Sasaki, Yasuhito; Kenmoku, Tomonori; Yamazaki, Hironori; Miyagi, Masayuki; Ohtori, Seiji; Takahashi, Kazuhisa

    2015-12-01

    This study evaluated dorsal root ganglia from C3-C7, analyzed gait, and compared the expression of calcitonin gene-related peptide (CGRP) which was a marker of inflammatory pain in a rat rotator cuff tear model in which the supraspinatus and infraspinatus tendons were detached; comparisons were made to a sham group in which only the tendons were exposed. Fluorogold was injected into the glenohumeral joint 21 days after surgery in both groups, and saline, steroids, or hyaluronic acid was injected into the glenohumeral joint in the rotator cuff tear group 26 days after surgery. The proportions of CGRP-immunoreactive neurons were higher and the gait parameters were impaired in the rotator cuff tear group compared to in the sham group. However, the CGRP expression was reduced and the gait was improved with steroid or hyaluronic acid injection compared to saline, suggesting that both hyaluronic acid and steroid injections suppressed of inflammation which thought to be provided pain relief. While there were no significant differences, the suppression of CGRP expression and the improved gait after hyaluronic acid and steroid injections suggested that both methods were effective for rat rotator cuff tear model.

  12. Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid

    PubMed Central

    Osti, Leonardo; Buda, Matteo; Buono, Angelo Del; Osti, Raffaella; Massari, Leo

    2015-01-01

    Summary Purpose the aim of this quantitative review is to document potential benefit and adverse effects of hyaluronic acid (HA) injection into the shoulder with rotator cuff tears. Methods a systematic literature search was performed in english PubMed, Medline, Ovid, Google Scholar and Embase databases using the combined key words “hyaluronic acid”, “rotator cuff tear”, “hyaluronate”, “shoulder”, “viscosupplementation”, with no limit regarding the year of publication. Articles were included if they reported data on clinical and functional outcomes, complications in series of patients who had undergone HA injection for management of rotator cuff tears. Two Authors screened the selected articles for title, abstract and full text in accordance with predefined inclusion and exclusion criteria. The papers were accurately analyzed focusing on objective rating scores reported. Results a total of 11 studies, prospective, 7 were randomized were included by full text. A total of 1102 patients were evaluated clinically after different HA injection compare with corticosteroid injection, physically therapies, saline solution injection and control groups. The use of HA in patients with rotator cuff tears improve VAS and functional score in all trials that we have analyzed. Conclusion intra-articular injection with HA is effective in reducing pain and improving function in shoulder with rotator cuff tears and without severe adverse reaction. Level of evidence Level I. PMID:26958534

  13. A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

    PubMed

    Fernández, Silvina; Córdoba, Mariana

    2017-04-01

    Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC.

  14. Cutaneous mucinosis in shar-pei dogs is due to hyaluronic acid deposition and is associated with high levels of hyaluronic acid in serum.

    PubMed

    Zanna, G; Fondevila, D; Bardagí, M; Docampo, M J; Bassols, A; Ferrer, L

    2008-10-01

    Cutaneous mucinosis affects primarily shar-pei dogs. Hyaluronic acid (HA) is considered to be the main component of mucin and CD44 is the major cell surface receptor of HA, necessary for its uptake and catabolism. The aims of this study were to identify the composition of the mucin in cutaneous mucinosis of shar-pei dogs, investigate the correlation between the deposition of HA and the expression of CD44, and determine whether shar-pei dogs with cutaneous mucinosis presented with elevated levels of serum HA. In skin biopsies, the mucinous material was stained intensely with Alcian blue and bound strongly by the hyaluronan-binding protein. No correlation was found between the degree of HA deposition in the dermis and the expression of CD44 in the skin of shar-pei dogs affected or unaffected by cutaneous mucinosis. A clear positive correlation was found between the existence of clinical mucinosis and the serum HA concentration. In control dogs, serum HA ranged from 155.53 to 301.62 microg L(-1) in shar-pei dogs; without mucinosis it ranged from 106.72 to 1251.76 microg L(-1) and in shar-pei dogs with severe mucinosis it ranged between 843.51 to 2330.03 microg L(-1). Altogether, the results reported here suggest that mucinosis of shar-pei dogs is probably the consequence of a genetic defect in the metabolism of HA.

  15. Efficacy and Safety of a Low-Molecular Weight Hyaluronic Acid Topical Gel in the Treatment of Facial Seborrheic Dermatitis

    PubMed Central

    Rowland Powell, Callie

    2012-01-01

    Objective: Hyaluronic acid sodium salt gel 0.2% is a topical device effective in reducing skin inflammation. Facial seborrheic dermatitis, characterized by erythema and or flaking/scaling in areas of high sebaceous activity, affects up to five percent of the United States population. Despite ongoing studies, the cause of the condition is yet unknown, but has been associated with yeast colonization and resultant immune-derived inflammation. First-line management typically is with topical steroids as well as the immunosuppressant agents pimecrolimus and tacrolimus. The objective of this study was to evaluate the efficacy and safety of a topical anti-inflammatory containing low-molecular weight hyaluronic acid. Design and setting: Prospective, observational, non-blinded safety and efficacy study in an outpatient setting. Participants: Individuals 18 to 75 years of age with facial seborrheic dermatitis. Measurements: Outcome measures included scale, erythema, pruritus, and the provider global assessment, which were all measured on a five-point scale. Subjects were assessed at Baseline, Week 2, Week 4, and Week 8. Results: Interim data for 7 of 15 subjects are presented. Hyaluronic acid sodium salt gel 0.2% was shown through visual grading assessments to improve the provider global assessment by 47.62 percent from Baseline to Week 4. Reductions in scale, erythema, and pruritus were 66.67, 50, and 60 percent, respectively at Week 4. At Week 8, the provider global assessment was improved from baseline in 100 percent of subjects. Conclusion: Treatment with topical low-molecular weight hyaluronic acid resulted in improvement in the measured endpoints. Topical low-molecular weight hyaluronic acid is another option that may be considered for the treatment of facial seborrheic dermatitis in the adult population. Compliance and tolerance were excellent. PMID:23125886

  16. Caution should be used in long-term treatment with oral compounds of hyaluronic acid in patients with a history of cancer.

    PubMed

    Simone, Procopio; Alberto, Migliore

    2015-11-01

    Intra-articular administration of hyaluronic acid is a valuable therapeutic tool for the management of patients with osteoarthritis. However, in recent years numerous formulations containing hyaluronic acid administrable by oral route have entered the market. Even if there are some data in the literature that have shown their effectiveness, systemic administration may expose a greater risk in certain situations. In fact, although hyaluronic acid is not considered a drug it is certain that it can interact with specific receptors and promote cell proliferation. This interaction may be potentially hazardous in cancer patients for which these oral formulations should be contraindicated.

  17. Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis.

    PubMed

    Araújo, J P; Silva, L; Andrade, R; Paços, M; Moreira, H; Migueis, N; Pereira, R; Sarmento, A; Pereira, H; Loureiro, N; Espregueira-Mendes, J

    2016-01-01

    The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current available literature, its recommendation in the current practice is still controversial. This study shows that ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid can improve pain, function and quality of life in patients with symptomatic and radiographic hip osteoarthritis. In addition, the administration of triamcinolone hexacetonide and hyaluronic acid to the hip joint in these patients can delay the need for interventional surgery.

  18. Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy.

    PubMed

    Yoon, Hong Yeol; Koo, Heebeom; Choi, Ki Young; Lee, So Jin; Kim, Kwangmeyung; Kwon, Ick Chan; Leary, James F; Park, Kinam; Yuk, Soon Hong; Park, Jae Hyung; Choi, Kuiwon

    2012-05-01

    Tumor-targeted imaging and therapy have been the challenging issue in the clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were synthesized by chemical conjugation of aminated 5β-cholanic acid, polyethylene glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers. Second, Ce6 was readily loaded into the HANPs by a simple dialysis method resulting in Ce6-loaded hyaluronic acid nanoparticles (Ce6-HANPs), wherein in the loading efficiency of Ce6 was higher than 80%. The resulting Ce6-HANPs showed stable nano-structure in aqueous condition and rapid uptake into tumor cells. In particular Ce6-HANPs were rapidly degraded by hyaluronidases abundant in cytosol of tumor cells, which may enable intracellular release of Ce6 at the tumor tissue. After an intravenous injection into the tumor-bearing mice, Ce6-HANPs could efficiently reach the tumor tissue via the passive targeting mechanism and specifically enter tumor cells through the receptor-mediated endocytosis based on the interactions between HA of nanoparticles and CD44, the HA receptor on the surface of tumor cells. Upon laser irradiation, Ce6 which was released from the nanoparticles could generate fluorescence and singlet oxygen inside tumor cells, resulting in effective suppression of tumor growth. Overall, it was demonstrated that Ce6-HANPs could be successfully applied to in vivo photodynamic tumor imaging and therapy simultaneously.

  19. Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid.

    PubMed

    Wang, Xiaodan; Gu, Xiangqin; Wang, Huimin; Sun, Yujiao; Wu, Haiyang; Mao, Shirui

    2017-01-01

    Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6-260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting.

  20. Hyaluronic acid grafted PLGA copolymer nanoparticles enhance the targeted delivery of Bromelain in Ehrlich's Ascites Carcinoma.

    PubMed

    Bhatnagar, Priyanka; Pant, Aditya Bhushan; Shukla, Yogeshwer; Panda, Amulya; Gupta, Kailash Chand

    2016-08-01

    Rapidly increasing malignant neoplastic disease demands immediate attention. Several dietary compounds have recently emerged as strong anti-cancerous agents. Among, Bromelain (BL), a protease from pineapple plant, was used to enhance its anti-cancerous efficacy using nanotechnology. In lieu of this, hyaluronic acid (HA) grafted PLGA copolymer, having tumor targeting ability, was developed. BL was encapsulated in copolymer to obtain BL-copolymer nanoparticles (NPs) that ranged between 140 to 281nm in size. NPs exhibited higher cellular uptake and cytotoxicity in cells with high CD44 expression as compared with non-targeted NPs. In vivo results on tumor bearing mice showed that NPs were efficient in suppressing the tumor growth. Hence, the formulation could be used as a self-targeting drug delivery cargo for the remission of cancer.

  1. Production of Hyaluronic Acid by Streptococcus zooepidemicus on Protein Substrates Obtained from Scyliorhinus canicula Discards

    PubMed Central

    Vázquez, José A.; Pastrana, Lorenzo; Piñeiro, Carmen; Teixeira, José A.; Pérez-Martín, Ricardo I.; Amado, Isabel R.

    2015-01-01

    This work investigates the production of hyaluronic acid (H) by Streptococcus equi subsp. zooepidemicus in complex media formulated with peptones obtained from Scyliorhinus canicula viscera by-products. Initially, in batch cultures, the greatest productions were achieved using commercial media (3.03 g/L) followed by peptones from alcalase hydrolyzed viscera (2.32 g/L) and peptones from non-hydrolyzed viscera (2.26 g/L). An increase of between 12% and 15% was found in subsequent fed-batch cultures performed on waste peptones. Such organic nitrogen sources were shown to be an excellent low-cost substrate for microbial H, saving more than 50% of the nutrient costs. PMID:26512678

  2. Management of Vesicoureteral Reflux by Endoscopic Injection of Dextranomer/Hyaluronic Acid in Adults

    PubMed Central

    Stark, Timothy W; Lacy, John M; Preston, David M

    2016-01-01

    A 74-year-old man presented for evaluation after discovery of a left bladder-wall tumor. He underwent transurethral resection of bladder tumor (TURBT) operation for treatment of low-grade, Ta urothelial cancer of the bladder. The patient developed recurrent disease and returned to the operating room for repeat TURBT, circumcision, and administration of intravesical mitomycin C. The patient developed balanitis xerotica obliterans 4 years post-circumcision, requiring self-dilation with a catheter. He subsequently developed 3 consecutive episodes of left-sided pyelonephritis. Further investigation with voiding cystourethrogram (VCUG) revealed Grade 3, left-sided vesicoureteral reflux (VUR). Due to existing comorbidities, the patient elected treatment with endoscopic dextranomer/hyaluronic acid injection. A post-operative VCUG demonstrated complete resolution of left-sided VUR. This patient has remained symptom free for 8 months post-injection, with no episodes of pyelonephritis. PMID:27162514

  3. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid

    NASA Astrophysics Data System (ADS)

    Singh, Anirudha; Corvelli, Michael; Unterman, Shimon A.; Wepasnick, Kevin A.; McDonnell, Peter; Elisseeff, Jennifer H.

    2014-10-01

    Lubrication is key for the efficient function of devices and tissues with moving surfaces, such as articulating joints, ocular surfaces and the lungs. Indeed, lubrication dysfunction leads to increased friction and degeneration of these systems. Here, we present a polymer-peptide surface coating platform to non-covalently bind hyaluronic acid (HA), a natural lubricant in the body. Tissue surfaces treated with the HA-binding system exhibited higher lubricity values, and in vivo were able to retain HA in the articular joint and to bind ocular tissue surfaces. Biomaterials-mediated strategies that locally bind and concentrate HA could provide physical and biological benefits when used to treat tissue-lubricating dysfunction and to coat medical devices.

  4. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  5. Hyaluronic acid is increased in the skin and urine in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Imai, T.; Yamauchi, M.; Nagao, K.

    1996-01-01

    We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

  6. Effect of hyaluronic acid in bone formation and its applications in dentistry.

    PubMed

    Zhao, Ningbo; Wang, Xin; Qin, Lei; Zhai, Min; Yuan, Jing; Chen, Ji; Li, Dehua

    2016-06-01

    Hyaluronic acid (HA), the simplest glycosaminoglycan, participates in several important biological procedures, including mediation of cellular signaling, regulation of cell adhesion and proliferation, and manipulation of cell differentiation. The effect of HA on cell proliferation and differentiation depends on its molecular weight (MW) and concentration. Moreover, the properties of high viscosity, elasticity, highly negative charge, biocompatibility, biodegradability, and nonimmunogenicity make HA attractive in tissue engineering and disease treatment. This review comprises an overview of the effect of HA on cell proliferation and differentiation in vitro, the role of HA in bone regeneration in vivo, and the clinical applications of HA in dentistry, focusing on the mechanism underlining the effect of MW and concentration of HA on cell proliferation and osteogenic differentiation. It is expected that practical progress of HA both in laboratory-based experiments and clinical applications will be achieved in the next few years. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1560-1569, 2016.

  7. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid.

    PubMed

    Singh, Anirudha; Corvelli, Michael; Unterman, Shimon A; Wepasnick, Kevin A; McDonnell, Peter; Elisseeff, Jennifer H

    2014-10-01

    Lubrication is key for the efficient function of devices and tissues with moving surfaces, such as articulating joints, ocular surfaces and the lungs. Indeed, lubrication dysfunction leads to increased friction and degeneration of these systems. Here, we present a polymer-peptide surface coating platform to non-covalently bind hyaluronic acid (HA), a natural lubricant in the body. Tissue surfaces treated with the HA-binding system exhibited higher lubricity values, and in vivo were able to retain HA in the articular joint and to bind ocular tissue surfaces. Biomaterials-mediated strategies that locally bind and concentrate HA could provide physical and biological benefits when used to treat tissue-lubricating dysfunction and to coat medical devices.

  8. Cheese whey: A cost-effective alternative for hyaluronic acid production by Streptococcus zooepidemicus.

    PubMed

    Amado, Isabel R; Vázquez, José A; Pastrana, Lorenzo; Teixeira, José A

    2016-05-01

    This study focuses on the optimisation of cheese whey formulated media for the production of hyaluronic acid (HA) by Streptococcus zooepidemicus. Culture media containing whey (W; 2.1g/L) or whey hydrolysate (WH; 2.4 g/L) gave the highest HA productions. Both W and WH produced high yields on protein consumed, suggesting cheese whey is a good nitrogen source for S. zooepidemicus production of HA. Polysaccharide concentrations of 4.0 g/L and 3.2g/L were produced in W and WH in a further scale-up to 5L bioreactors, confirming the suitability of the low-cost nitrogen source. Cheese whey culture media provided high molecular weight (>3000 kDa) HA products. This study revealed replacing the commercial peptone by the low-cost alternative could reduce HA production costs by up to a 70% compared to synthetic media.

  9. Control hydrogel-hyaluronic acid aggregation toward the design of biomimetic superlubricants.

    PubMed

    Seekell, Raymond P; Dever, Rachel; Zhu, Yingxi

    2014-07-14

    Healthy synovial fluids (SFs) are complex fluids consisting of biopolymers, globule proteins, and lipids and regarded as superlubricants to provide nearly life-long low friction and wear protection of synovial joints in mammals. In this paper, we report that the intricate lubricious mixture can be simulated by the aggregation of hyaluronic acid (HA) and hydrogel particles in aqueous suspensions. In the HA aqueous suspensions added with synthetic polymer microgels, we have effectively captured the bulk rheological properties of healthy SFs. It is also confirmed by light scattering and fluorescence microscopic characterization that added hydrogel particles can enhance the HA network by hydrogel-mediated hydrogen bonding, leading to the fractal HA-hydrogel aggregating networks in aqueous suspensions. The potential application of HA-hydrogel particle aggregates as biomimetic superlubricants is supported by the comparable low friction at high load to that of healthy SFs.

  10. Ionically cross-linked hyaluronic acid: wetting, lubrication, and viscoelasticity of a modified adhesion barrier gel

    PubMed Central

    Vorvolakos, Katherine; Isayeva, Irada S; Luu, Hoan-My Do; Patwardhan, Dinesh V; Pollack, Steven K

    2011-01-01

    Hyaluronic acid (HA), in linear or cross-linked form, is a common component of cosmetics, personal care products, combination medical products, and medical devices. In all cases, the ability of the HA solution or gel to wet surfaces and/or disrupt and lubricate interfaces is a limiting feature of its mechanism of action. We synthesized ferric ion–cross-linked networks of HA based on an adhesion barrier, varied the degree of cross-linking, and performed wetting goniometry, viscometry, and dynamic mechanical analysis. As cross-linking increases, so do contact angle, viscosity, storage modulus, and loss modulus; thus, wetting and lubrication are compromised. These findings have implications in medical device materials, such as adhesion barriers and mucosal drug delivery vehicles. PMID:22915924

  11. Stable emulsions prepared by self-assembly of hyaluronic acid and chitosan for papain loading.

    PubMed

    Zhao, Donghua; Wei, Wei; Zhu, Ye; Sun, Jianhua; Hu, Qiong; Liu, Xiaoya

    2015-04-01

    A simple, green and effective process is developed to fabricate hyaluronic acid (HA)/chitosan (CS) complex colloidal particles through electrostatic interactions. The obtained complexes can be used as biocompatible emulsifiers and novel potential carriers for papain loading. An HA/CS mass ratio of 2 is the optimal condition leading to the smallest Dh (420.9 nm). The complexes with eight different mass ratios are used to stabilize white oil/water emulsions. The structure of the complexes at the oil-water interface varies in response to the mass ratio and can be classified into two typical structures, similar to typical polymeric surfactants and solid particulate emulsifiers. Furthermore, papain is introduced into the complex systems. Formation of the papain/HA/CS complexes in a compact form can protect the enzyme. Here, a novel strategy is introduced to fabricate a biocompatible emulsion from the HA/CS complexes and demonstrate that the stable complex is a suitable enzyme delivery system.

  12. Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer.

    PubMed

    Kurioka, T; Mizutari, K; Niwa, K; Fukumori, T; Inoue, M; Hasegawa, M; Shiotani, A

    2016-02-01

    Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non-genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss.

  13. Loss of glycogen debranching enzyme AGL drives bladder tumor growth via induction of hyaluronic acid synthesis

    PubMed Central

    Guin, Sunny; Ru, Yuanbin; Agarwal, Neeraj; Lew, Carolyn R.; Owens, Charles; Comi, Giacomo P.; Theodorescu, Dan

    2015-01-01

    Purpose We demonstrated that Amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) is a tumor growth suppressor and prognostic marker in human bladder cancer. Here we determine how AGL loss enhances tumor growth, hoping to find therapeutically tractable targets/pathways that could be used in patients with low AGL expressing tumors. Experimental Design We transcriptionally profiled bladder cell lines with different AGL expression. By focusing on transcripts overexpressed as a function of low AGL and associated with adverse clinicopathologic variables in human bladder tumors, we sought to increase the chances of discovering novel therapeutic opportunities. Results One such transcript was hyaluronic acid synthase 2 (HAS2), an enzyme responsible for hyaluronic acid (HA) synthesis. HAS2 expression was inversely proportional to that of AGL in bladder cancer cells and immortalized and normal urothelium. HAS2 driven HA synthesis was enhanced in bladder cancer cells with low AGL and this drove anchorage dependent and independent growth. siRNA mediated depletion of HAS2 or inhibition of HA synthesis by 4-Methylumbelliferone (4MU) abrogated in vitro and xenograft growth of bladder cancer cells with low AGL. AGL and HAS2 mRNA expression in human tumors was inversely correlated in patient datasets. Patients with high HAS2 and low AGL tumor mRNA expression had poor survival lending clinical support to xenograft findings that HAS2 drives growth of tumors with low AGL. Conclusion Our study establishes HAS2 mediated HA synthesis as a driver of growth of bladder cancer with low AGL and provides preclinical rationale for personalized targeting of HAS2/HA signaling in patients with low AGL expressing tumors. PMID:26490312

  14. Evaluation of liver fibrosis in patients with thalassemia: the important role of hyaluronic acid.

    PubMed

    Papastamataki, Maria; Delaporta, Polyxeni; Premetis, Evangelos; Kattamis, Antonios; Ladis, Vassilios; Papassotiriou, Ioannis

    2010-10-15

    Patients with transfusion-dependent thalassemia major often develop liver fibrosis due to liver iron overload and/or hepatitis virus C (HCV) infection. Hyaluronic acid (HA) plays a prominent role in the pathogenesis of liver fibrosis and the elevation of serum HA concentration is due to either increased synthesis by inflammatory cells and hepatic stellate cells or impaired degradation by sinusoidal endothelial cells (SECs) and thus is proposed as a non-invasive biomarker of liver fibrosis either by itself and/or included in the Hepascore formula. In this study we evaluated prospectively a screening of liver fibrosis in 201 adult patients aged 19-54 years with transfusion-dependent thalassemia major, based on HA measurements. 41/201 patients were HCV-RNA (+). HA was measured with a turbidimetric assay applied on a clinical chemistry analyzer. The Hepascore was computed from the results by using the model previously published. The main results of the study showed that: a) HA levels were increased in 110/201 (55%) thalassemia patients 85.0 ± 10.3 ng/ml, ranged from 15.0 to 1495.0 μg/l, compared to 20.8 ± 7.4 μg/l reference laboratory values, p<0.001, b) HA levels were significantly higher in HCV-RNA(+) compared to HCV-RNA(-) patients, 171.6 ± 202 vs 53.8 ± 35.5 μg/l, p<0.0001 c) no significant correlations were found between HA levels and/or Hepascore with ferritin and liver iron content (LIC) assessed with MRI (p>0.324 and p>0.270, respectively). Our findings indicate that hyaluronic acid measurements contribute to the assessment of liver fibrosis in patients with thalassemia and might be helpful for further evaluation of patients with liver biopsy if this is truly needed. Furthermore, liver fibrosis in thalassemia seems to be independent from liver siderosis.

  15. Hyaluronic acid-bound letrozole nanoparticles restore sensitivity to letrozole-resistant xenograft tumors in mice.

    PubMed

    Nair, Hareesh B; Huffman, Steven; Veerapaneni, Poornachand; Kirma, Nameer B; Binkley, Peter; Perla, Rao P; Evans, Dean B; Tekmal, Rajeshwar R

    2011-05-01

    Letrozole is a potent aromatase inhibitor and superior to other defined selective estrogen receptor modulators such as tamoxifen in treating hormone-responsive postmenopausal breast cancer patients. Patients who receive this drug may become insensitive to the effects of estrogen deprivation induced by letrozole. Letrozole has known side effects on bone metabolism due to systemic ablation of estrogen production. The purpose of this study was to examine the therapeutic efficacy of hyaluronic acid-bound letrozole nanoparticles (HA-Letr-NPs) in restoring sensitivity to letrozole-resistant (LTLT-Ca) cells. To target letrozole to LTLT-Ca cells, hyaluronic acid-bound letrozole nanoparticles were prepared by nanoprecipitation using biodegradable PLGA-PEG co-polymer. Binding specificity of HA to CD44 on the cell surface was analyzed in vitro using FITC-CD44 Ab and CD44 siRNA by flow cytometry. Effects on in vitro cytotoxicity and aromatase enzymatic activity of HA-Letr-NPs were performed in MCF-7 breast cancer cells, MCF-7 cells over-expressing aromatase (MCF-7/Aro), and LTLT-Ca cells resistant to letrozole. Preclinical efficacy of HA-Letr-NPs was examined in mice using LTLT-Ca xenograft tumors. HA-Letr-NPs were restricted to a maximum size of 100 nm. The in vitro drug release assay showed that the highest released concentration of letrozole occurred after 23 hours at 37 degrees C in phosphate-buffered saline. HA-Letr-NPs on MCF-7/Aro and LTLT-Ca cells showed an IC50 of 2 microM and 5 microM, respectively. HA-Letr-NPs were more efficacious in inhibiting tumor growth, reducing in vitro cellular and in vivo tumor aromatase enzyme activity more than the corresponding Letr-NPs or letrozole. HA-Letr-NPs restored and maintained a prolonged sensitivity and targeted delivery of letrozole in letrozole-resistant tumors in vivo.

  16. β-TCP granules mixed with reticulated hyaluronic acid induce an increase in bone apposition.

    PubMed

    Aguado, Eric; Pascaretti-Grizon, Florence; Gaudin-Audrain, Christine; Goyenvalle, Eric; Chappard, Daniel

    2014-02-01

    β beta-tricalcium phosphate (β-TCP) granules are suitable for repair of bone defects. They have an osteoconductive effect shortly after implantation. However, dry granules are difficult to handle in the surgical room because of low weight and lack of cohesion. Incorporation of granules in a hydrogel could be a satisfactory solution. We have investigated the use of hyaluronic acid (HyA) as an aqueous binder of the granules. β-TCP granules were prepared by the polyurethane foam technology. Commercially available linear (LHya) and reticulated hyaluronic acid (RHyA) in aqueous solution were used to prepare a pasty mixture that can be handled more easily than granules alone. Thirteen New Zealand White rabbits (3.5-3.75 kg) were used; a 4 mm hole was drilled in each femoral condyle. After flushing, holes were filled with either LHyA, RHyA, dry β-TCP granules alone, β-TCP granules + LHyA and β-TCP granules + RHyA. Rabbits were allowed to heal for one month, sacrificed and femurs were harvested and analysed by microCT and histomorphometry. The net amount of newly formed bone was derived from measurements done after thresholding the microCT images for the material and for the material+bone. LHyA and RHyA did not result in healing of the grafted area. LHyA was rapidly eluted from the grafted zone but allowed deposition of more granules, although the amount of formed bone was not significantly higher than with β-TCP granules alone. RHyA permitted the deposition of more granules which induced significantly more bone trabeculae without inducing an inflammatory reaction. RHyA appears to be a good vehicle to implant granules of β-TCP, since HyA does not interfere with bone remodeling.

  17. Bone-defects healing by high-molecular hyaluronic acid: preliminary results

    PubMed Central

    Baldini, Alberto; Zaffe, Davide; Nicolini, Gabriella

    2010-01-01

    Summary Aim. The aim of this study is to evaluate the capability of Hyaloss™ matrix (Fab – Fidia Advanced Biopolymers – Pd – Italy), a biomaterial based on hyaluronic acid, used as organic scaffold in bone repair in post-extractive defects. Materials and methods: 20 post-extractive sockets were selected, with similar size defects in the same patient and in the same hemiarch. Hyaluronic acid with high molecular weight (Hyaloss™ matrix, Fab – Pd – Italy) was mixed with autologous bone obtained using Safescraper® curve (Meta – Re – Italy) to repair post-extractive sites. Safescraper® is a cutting edge system that allows to the collection of autologous bone without using traditional, incision-based collection techniques, which could cause discomfort to the patient. Results: Clinical and hystological evaluations were performed, four months after grafting, in the maxilla and in the mandible. From a clinical point of view Hyaloss™ matrix mixed with autologous bone and patient’s blood becomes a substance similar to gel, which is easy to insert in to the defect. From a hystological point of view, in the treated site there is the presence of an erosive activity, with accelerated angiogenetic and bone remodelling activities. Conclusions: The preliminary results show an acceleration of the bone deposit process and of its remodelling due to the presence of Hyaloss™ matrix, which, from a clinical point of view, improves the handling and application of the bone matrix inside the defects and, from a hystologic point of view makes it possible to obtain bone regeneration in less time when it is used with autologous bone. PMID:22238698

  18. TARGETING HYALURONIDASE FOR CANCER THERAPY: ANTITUMOR ACTIVITY OF SULFATED HYALURONIC ACID IN PROSTATE CANCER CELLS

    PubMed Central

    Benitez, Anaid; Yates, Travis J.; Lopez, Luis E.; Cerwinka, Wolfgang H.; Bakkar, Ashraf; Lokeshwar, Vinata B.

    2011-01-01

    The tumor cell-derived hyaluronidase HYAL-1 degrades hyaluronic acid (HA) into pro-angiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is a HAase inhibitor. In this study we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility and invasion of LNCaP, LNCaP-AI, DU145 and LAPC-4 prostate cancer cells, also inducing caspase 8-dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR-activity, NFkb activation and VEGF expression. These effects were traced to a blockade in complex formation between PI3K and HA receptors and to a transcriptional downregulation of HA receptors, CD44 and RHAMM, along with PI3K inhibition. Angiogenic HA fragments or overexpression of myristoylated-Akt or HA receptors blunted these effects of sHA, implicating a feedback loop between HA receptors and PI3K/Akt signaling in the mechanism of action. In an animal model, sHA strongly inhibited LNCaP-AI prostate tumor growth without causing weight loss or apparent serum-organ toxicity. Inhibition of tumor growth was accompanied by a significant decrease in tumor angiogenesis and an increase in apoptosis index. Taken together, our findings offer mechanistic insights into the tumor-associated HA-HAase system and a preclinical proof-of-concept of the safety and efficacy of sHA to control prostate cancer growth and progression. PMID:21555367

  19. Evaluation of Hyaluronic Acid Dilutions at Different Concentrations Using a Quartz Crystal Resonator (QCR) for the Potential Diagnosis of Arthritic Diseases

    PubMed Central

    Ahumada, Luis Armando Carvajal; González, Marco Xavier Rivera; Sandoval, Oscar Leonardo Herrera; Olmedo, José Javier Serrano

    2016-01-01

    The main objective of this article is to demonstrate through experimental means the capacity of the quartz crystal resonator (QCR) to characterize biological samples of aqueous dilutions of hyaluronic acid according to their viscosity and how this capacity may be useful in the potential diagnosis of arthritic diseases. The synovial fluid is viscous due to the presence of hyaluronic acid, synthesized by synovial lining cells (type B), and secreted into the synovial fluid thus making the fluid viscous. In consequence, aqueous dilutions of hyaluronic acid may be used as samples to emulate the synovial fluid. Due to the viscoelastic and pseudo-plastic behavior of hyaluronic acid, it is necessary to use the Rouse model in order to obtain viscosity values comparable with viscometer measures. A Fungilab viscometer (rheometer) was used to obtain reference measures of the viscosity in each sample in order to compare them with the QCR prototype measures. PMID:27879675

  20. Evaluation of Hyaluronic Acid Dilutions at Different Concentrations Using a Quartz Crystal Resonator (QCR) for the Potential Diagnosis of Arthritic Diseases.

    PubMed

    Ahumada, Luis Armando Carvajal; González, Marco Xavier Rivera; Sandoval, Oscar Leonardo Herrera; Olmedo, José Javier Serrano

    2016-11-22

    The main objective of this article is to demonstrate through experimental means the capacity of the quartz crystal resonator (QCR) to characterize biological samples of aqueous dilutions of hyaluronic acid according to their viscosity and how this capacity may be useful in the potential diagnosis of arthritic diseases. The synovial fluid is viscous due to the presence of hyaluronic acid, synthesized by synovial lining cells (type B), and secreted into the synovial fluid thus making the fluid viscous. In consequence, aqueous dilutions of hyaluronic acid may be used as samples to emulate the synovial fluid. Due to the viscoelastic and pseudo-plastic behavior of hyaluronic acid, it is necessary to use the Rouse model in order to obtain viscosity values comparable with viscometer measures. A Fungilab viscometer (rheometer) was used to obtain reference measures of the viscosity in each sample in order to compare them with the QCR prototype measures.

  1. A new highly viscoelastic hyaluronic acid gel: rheological properties, biocompatibility and clinical investigation in esthetic and restorative surgery.

    PubMed

    Iannitti, Tommaso; Bingöl, Ali Ö; Rottigni, Valentina; Palmieri, Beniamino

    2013-11-18

    Nowadays there is an increased demand for safe and effective volume enhancing fillers to achieve soft tissue augmentation in order to overcome tissue defects and aging-associated skin changes. In the present study we characterized the rheological and biological properties of Variofill(®), a new highly viscoelastic hyaluronic acid gel, by investigating the local effects following subcutaneous implantation in the rat to detect the host-tissue reactions and biodegradation over 18 months. We also investigated, for the first time, the application of Variofill(®) in esthetic and restorative surgery in two medical case reports. In the first case report we successfully performed Variofill(®) treatment to improve facial scars in a patient previously involved in a car crash. In the second case report we carried out a novel procedure involving a high-dose (1000 ml) injection of Variofill(®) into the dermis and subcutis of the abdominal quadrants in order to allow a classic reconstructive procedure of the abdominal wall in a patient presenting a wide incisional hernia.

  2. MRI evaluation of injectable hyaluronic acid-based hydrogel therapy to limit ventricular remodeling after myocardial infarction.

    PubMed

    Dorsey, Shauna M; McGarvey, Jeremy R; Wang, Hua; Nikou, Amir; Arama, Leron; Koomalsingh, Kevin J; Kondo, Norihiro; Gorman, Joseph H; Pilla, James J; Gorman, Robert C; Wenk, Jonathan F; Burdick, Jason A

    2015-11-01

    Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine magnetic resonance imaging (MRI) assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI.

  3. MRI Evaluation of Injectable Hyaluronic Acid-Based Hydrogel Therapy to Limit Ventricular Remodeling after Myocardial Infarction

    PubMed Central

    Dorsey, Shauna M.; McGarvey, Jeremy R.; Wang, Hua; Nikou, Amir; Arama, Leron; Koomalsingh, Kevin J.; Kondo, Norihiro; Gorman, Joseph H.; Pilla, James J.; Gorman, Robert C.; Wenk, Jonathan F.; Burdick, Jason A.

    2015-01-01

    Injectable biomaterials are an attractive therapy to attenuate left ventricular (LV) remodeling after myocardial infarction (MI). Although studies have shown that injectable hydrogels improve cardiac structure and function in vivo, temporal changes in infarct material properties after treatment have not been assessed. Emerging imaging and modeling techniques now allow for serial, non-invasive estimation of infarct material properties. Specifically, cine MRI assesses global LV structure and function, late-gadolinium enhancement (LGE) MRI enables visualization of infarcted tissue to quantify infarct expansion, and spatial modulation of magnetization (SPAMM) tagging provides passive wall motion assessment as a measure of tissue strain, which can all be used to evaluate infarct properties when combined with finite element (FE) models. In this work, we investigated the temporal effects of degradable hyaluronic acid (HA) hydrogels on global LV remodeling, infarct thinning and expansion, and infarct stiffness in a porcine infarct model for 12 weeks post-MI using MRI and FE modeling. Hydrogel treatment led to decreased LV volumes, improved ejection fraction, and increased wall thickness when compared to controls. FE model simulations demonstrated that hydrogel therapy increased infarct stiffness for 12 weeks post-MI. Thus, evaluation of myocardial tissue properties through MRI and FE modeling provides insight into the influence of injectable hydrogel therapies on myocardial structure and function post-MI. PMID:26280951

  4. Intra-articular hyaluronic acid after knee arthroscopy: a two-year study.

    PubMed

    Hempfling, Harald

    2007-05-01

    Arthroscopic knee joint lavage is used when conservative treatment of knee osteoarthritis is unsatisfactory and a joint prosthesis is not yet indicated. The potentially negative effect of irrigation fluids on cartilage metabolism and structure has led to the development of a temporary synovial fluid substitute containing hyaluronic acid. The short and long-term effects of this synovial fluid substitute were investigated in a total of 80 patients with persistent knee pain. Forty patients underwent arthroscopic knee joint lavage, in some cases combined with careful cartilage debridement (group A) while a further 40 patients underwent the same procedure which, after final joint lavage, was immediately followed by a single instillation of 10 ml of the synovial fluid substitute (0.5% sodium hyaluronate) into the joint (A + HA group). After the procedure, pain on walking and restricted ability to walk 100 m were markedly reduced to a comparable extent in both groups. Three months later, the effect of the treatment assessed using various parameters (CGI, restricted ability to walk 100 m, pain on walking, night pain) had decreased in group A, while it remained stable or even improved slightly in the A + HA group. The Mann-Whitney statistics revealed a descriptive superiority for the A + HA group at this time point. One year after treatment the superiority of the A + HA group was confirmed using the same assessment parameters. No side effects or adverse events were observed for either treatment procedure. This study shows that arthroscopic knee joint lavage leads to a lasting improvement in pain and functional impairment. The post-arthroscopic instillation of a HA-based synovial fluid substitute into the joint is a suitable way of achieving long-term stabilisation of the treatment outcome. This was supported by findings of a survey of 66 patients at 2 years after treatment in this study. Level I prospective, randomised controlled double-blind study.

  5. Hyaluronic Acid (HA) Viscosupplementation on Synovial Fluid Inflammation in Knee Osteoarthritis: A Pilot Study

    PubMed Central

    Vincent, Heather K; Percival, Susan S; Conrad, Bryan P; Seay, Amanda N; Montero, Cindy; Vincent, Kevin R

    2013-01-01

    Objective: This study examined the changes in synovial fluid levels of cytokines, oxidative stress and viscosity six months after intraarticular hyaluronic acid (HA) treatment in adults and elderly adults with knee osteoarthritis (OA). Design: This was a prospective, repeated-measures study design in which patients with knee OA were administered 1% sodium hyaluronate. Patients (N=28) were stratified by age (adults, 50-64 years and elderly adults, ≥65 years). Ambulatory knee pain values and self-reported physical activity were collected at baseline and month six. Materials and Methods: Knee synovial fluid aspirates were collected at baseline and at six months. Fluid samples were analyzed for pro-inflammatory cytokines (interleukins 1β, 6,8,12, tumor necrosis factor-α, monocyte chemotactic protein), anti-inflammatory cytokines (interleukins 4, 10 13), oxidative stress (4-hydroxynonenal) and viscosity at two different physiological shear speeds 2.5Hz and 5Hz. Results: HA improved ambulatory knee pain in adults and elderly groups by month six, but adults reported less knee pain-related interference with participation in exercise than elderly adults. A greater reduction in TNF-α occurred in adults compared to elderly adults (-95.8% ± 7.1% vs 19.2% ± 83.8%, respectively; p=.044). Fluid tended to improve at both shear speeds in adults compared to the elderly adults. The reduction in pain severity correlated with the change in IL-1β levels by month six (r= -.566; p=.044). Conclusion: Reduction of knee pain might be due to improvements in synovial fluid viscosity and inflammation. Cartilage preservation may be dependent on how cytokine, oxidative stress profiles and viscosity change over time. PMID:24093052

  6. Protein binding assay for hyaluronate

    SciTech Connect

    Lacy, B.E.; Underhill, C.B.

    1986-11-01

    A relatively quick and simple assay for hyaluronate was developed using the specific binding protein, hyaluronectin. The hyaluronectin was obtained by homogenizing the brains of Sprague-Dawley rats, and then centrifuging the homogenate. The resulting supernatant was used as a source of crude hyaluronectin. In the binding assay, the hyaluronectin was mixed with (/sup 3/H)hyaluronate, followed by an equal volume of saturated (NH/sub 4/)/sub 2/SO/sub 4/, which precipitated the hyaluronectin and any (/sup 3/H)hyaluronate associated with it, but left free (/sup 3/H)hyaluronate in solution. The mixture was then centrifuged, and the amount of bound (/sup 3/H)hyaluronate in the precipitate was determined. Using this assay, the authors found that hyaluronectin specifically bound hyaluronate, since other glycosaminoglycans failed to compete for the binding protein. In addition, the interaction between hyaluronectin and hyaluronate was of relatively high affinity, and the size of the hyaluronate did not appear to substantially alter the amount of binding. To determine the amount of hyaluronate in an unknown sample, they used a competition assay in which the binding of a set amount of (/sup 3/H)hyaluronate was blocked by the addition of unlabeled hyaluronate. By comparing the degree of competition of the unknown samples with that of known amounts of hyaluronate, it was possible to determine the amount of hyaluronate in the unknowns. They have found that this method is sensitive to 1 ..mu..g or less of hyaluronate, and is unaffected by the presence of proteins.

  7. Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer.

    PubMed

    Lin, Tingsheng; Yuan, Ahu; Zhao, Xiaozhi; Lian, Huibo; Zhuang, Junlong; Chen, Wei; Zhang, Qing; Liu, Guangxiang; Zhang, Shiwei; Chen, Wei; Cao, Wenmin; Zhang, Chengwei; Wu, Jinhui; Hu, Yiqiao; Guo, Hongqian

    2017-02-15

    Bladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable when bladder cancer progresses to a muscle-invasive disease. However, cystectomy still causes a high risk of death and a low quality of life (such as ureter-abdomen ostomy, uroclepsia for ileal-colon neobladder). Therefore, more effective treatments as well as bladder preservation are needed. We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancer, which show high tumor selectivity, high treatment efficacy, good bioavailability, and excellent biocompatibility. The nanoparticles demonstrated a stable spherical nanostructure in aqueous conditions with good mono-dispersity, and their average size was 171.3±9.14nm. The nanoparticles can be degraded by hyaluronidase when it is over-expressed in bladder cells; therefore, they appear to have a hyaluronidase-responsive "OFF/ON" behavior of a fluorescence signal. HA-IR-780 NPs also showed high photothermal efficiency; 2.5, 5, 10 and 20μg/mL of NPs had a maximum temperature increase of 11.2±0.66°C, 18.6±0.75°C, 26.8±1.11°C and 32.3±1.42°C. The in vitro cell viability showed that MB-49 cells could be efficiently ablated by combining HA-IR-780 NPs with 808nm laser irradiation. Then, in vivo biodistribution showed the HA-IR-780 NPs are targeted for accumulation in bladder cancer cells but have negligible accumulation in normal bladder wall. The photothermal therapeutic efficacy of HA-IR-780 NPs in the orthotopic bladder cancer model showed tumors treated with NPs had a maximum temperature of 48.1±1.81°C after 6min of laser irradiation. The tumor volume was approximately 65-75mm(3) prior to treatment. After 12days, the tumor sizes for the PBS, PBS plus laser irradiation and HA-IR-780 NPs-treated groups were 784.75mm(3), 707.5mm(3), and 711.37mm(3), respectively. None of the tumors in the HA-IR-780

  8. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    NASA Astrophysics Data System (ADS)

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-08-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of Un

  9. Self-assembled ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates for targeted gene delivery.

    PubMed

    Liang, Kun; Bae, Ki Hyun; Lee, Fan; Xu, Keming; Chung, Joo Eun; Gao, Shu Jun; Kurisawa, Motoichi

    2016-03-28

    Nanosized polyelectrolyte complexes are attractive delivery vehicles for the transfer of therapeutic genes to diseased cells. Here we report the application of self-assembled ternary complexes constructed with plasmid DNA, branched polyethylenimine and hyaluronic acid-green tea catechin conjugates for targeted gene delivery. These conjugates not only stabilize plasmid DNA/polyethylenimine complexes via the strong DNA-binding affinity of green tea catechin, but also facilitate their transport into CD44-overexpressing cells via receptor-mediated endocytosis. The hydrodynamic size, surface charge and physical stability of the complexes are characterized. We demonstrate that the stabilized ternary complexes display enhanced resistance to nuclease attack and polyanion-induced dissociation. Moreover, the ternary complexes can efficiently transfect the difficult-to-transfect HCT-116 colon cancer cell line even in serum-supplemented media due to their enhanced stability and CD44-targeting ability. Confocal microscopic analysis demonstrates that the stabilized ternary complexes are able to promote the nuclear transport of plasmid DNA more effectively than binary complexes and hyaluronic acid-coated ternary complexes. The present study suggests that the ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates can be widely utilized for CD44-targeted delivery of nucleic acid-based therapeutics.

  10. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis

    PubMed Central

    Vilar, José M.; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M.; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J.; Carrillo, José M.

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs. PMID:26886592

  11. [Effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis].

    PubMed

    Gadek, Artur; Miśkowiec, Krzysztof; Wordliczek, Jerzy; Liszka, Henryk

    2011-01-01

    Osteoarthritis (OA) is one of the leading causes of disability in the elderly. The changes in the lubricating properties of synovial fluid lead to significant pain and loss of function. Viscosupplemen-tation, in which hyaluronic acid (HA) is injected into the knee joint, has evolved into an important part of our current therapeutic regimen in addressing the patient with knee pain due to OA. Intra-articular HA or hylan have proven to be an effective, safe, and tolerable treatment for symptomatic knee OA. In an effort to limit cardiovascular, gastrointestinal, and renal safety concerns with COX-2 selective and nonselective NSAIDs and maximize HA efficacy, it is even proposed using HA earlier in the treatment paradigm for knee OA and also as part of a comprehensive treatment strategy. Our study reconfirmed effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis.

  12. Conflict of interest in the assessment of hyaluronic acid injections for osteoarthritis of the knee: an updated systematic review.

    PubMed

    Printz, Jonathon O; Lee, John J; Knesek, Michael; Urquhart, Andrew G

    2013-09-01

    The search results of a recent systematic review of prospective, randomized, placebo-controlled trials on hyaluronic acid injections for knee arthritis were updated and reviewed for funding source and qualitative conclusions. Forty-eight studies were identified; 30 (62.5%) were industry funded, and 3 (6.25%) were not. Fifteen (31.3%) studies did not identify a funding source. An association was observed between a reported potential financial conflict of interest of the author and the qualitative conclusion (P=0.018). None of the studies with a reported financial conflict of interest of at least one author had an unfavorable conclusion; 11 (35%) of the 31 studies with no industry-affiliated authors indicated that hyaluronic acid injection for knee osteoarthritis was no more effective than a placebo injection.

  13. Hyaluronic acid conjugates as vectors for the active targeting of drugs, genes and nanocomposites in cancer treatment.

    PubMed

    Arpicco, Silvia; Milla, Paola; Stella, Barbara; Dosio, Franco

    2014-03-17

    Hyaluronic acid (HA) is a naturally-occurring glycosaminoglycan and a major component of the extracellular matrix. Low levels of the hyaluronic acid receptor CD44 are found on the surface of epithelial, hematopoietic, and neuronal cells; it is overexpressed in many cancer cells, and in particular in tumor-initiating cells. HA has recently attracted considerable interest in the field of developing drug delivery systems, having been used, as such or encapsulated in different types of nanoassembly, as ligand to prepare nano-platforms for actively targeting drugs, genes, and diagnostic agents. This review describes recent progress made with the several chemical strategies adopted to synthesize conjugates and prepare novel delivery systems with improved behaviors.

  14. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis.

    PubMed

    Vilar, José M; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J; Carrillo, José M

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.

  15. A Lanthanum-Tagged Chemotherapeutic Agent HA-Pt to Track the In Vivo Distribution of Hyaluronic Acid Complexes

    PubMed Central

    Forrest, W.C.; Cai, Shuang; Aires, Daniel; Forrest, M. Laird

    2015-01-01

    Hyaluronic acid drug conjugates can target anti-cancer drugs directly to tumor tissue for loco-regional treatment with enhanced bioavailability, local efficacy and reduced toxicity. In this study, the distribution and pharmacokinetics of hyaluronic acid carrier and a conjugated cisplatin anti-cancer drug were tracked by lanthanum (III) [La(III)] affinity tagging of the nanocarrier. The strong binding affinity of La(III) to HA enabled the simple preparation of a physiologically stable complex HA-Pt-La and straightforward simultaneous detection of HA-La and Pt in biological matrices using inductively coupled plasma-mass spectrometry (ICP-MS). Consequently, after subcutaneous injection of HA-Pt-La nanoparticles in human head and neck squamous cell carcinoma (HNSCC) tumor-bearing mice, the HA and Pt content were detected and quantified simultaneously in the plasma, primary tumor, liver and spleen. PMID:26756040

  16. Co-culture of vascular endothelial cells and smooth muscle cells by hyaluronic acid micro-pattern on titanium surface

    NASA Astrophysics Data System (ADS)

    Li, Jingan; Li, Guicai; Zhang, Kun; Liao, Yuzhen; Yang, Ping; Maitz, Manfred F.; Huang, Nan

    2013-05-01

    Micro-patterning as an effective bio-modification technique is increasingly used in the development of biomaterials with superior mechanical and biological properties. However, as of now, little is known about the simultaneous regulation of endothelial cells (EC) and smooth muscle cells (SMC) by cardiovascular implants. In this study, a co-culture system of EC and SMC was built on titanium surface by the high molecular weight hyaluronic acid (HMW-HA) micro-pattern. Firstly, the micro-pattern sample with a geometry of 25 μm wide HMW-HA ridges, and 25 μm alkali-activated Ti grooves was prepared by microtransfer molding (μTM) for regulating SMC morphology. Secondly, hyaluronidase was used to decompose high molecular weight hyaluronic acid into low molecular weight hyaluronic acid which could promote EC adhesion. Finally, the morphology of the adherent EC was elongated by the SMC micro-pattern. The surface morphology of the patterned Ti was imaged by SEM. The existence of high molecular weight hyaluronic acid on the modified Ti surface was demonstrated by FTIR. The SMC micro-pattern and EC/SMC co-culture system were characterized by immunofluorescence microscopy. The nitric oxide release test and cell retention calculation were used to evaluate EC function on inhibiting hyperplasia and cell shedding, respectively. The results indicate that EC in EC/SMC co-culture system displayed a higher NO release and cell retention compared with EC cultured alone. It can be suggested that the EC/SMC co-culture system possessed superiority to EC cultured alone in inhibiting hyperplasia and cell shedding at least in a short time of 24 h.

  17. Comparative evaluation of coenzyme Q10-based gel and 0.8% hyaluronic acid gel in treatment of chronic periodontitis

    PubMed Central

    Sharma, Varun; Gupta, Rajan; Dahiya, Parveen; Kumar, Mukesh

    2016-01-01

    Background: The anti-inflammatory and immune enhancing effects of coenzyme Q10 (CoQ10) and hyaluronic acid are well established in medical literature. The present study was undertaken to evaluate their role in chronic periodontitis. Materials and Methods: One hundred twenty sites in 24 patients with clinically confirmed periodontitis were included in the study. A split-mouth design was used for intrasulcular application of CoQ10 as adjunct to scaling and root planing (SRP), 0.8% hyaluronic acid as adjunct to SRP and SRP alone. Clinical parameters such as plaque index (PI), gingival color change index (GCCI), Eastman interdental bleeding index (EIBI), pocket depth (PD), and clinical attachment level (CAL) were recorded. All the clinical parameters PI, EIBI, GCCI, PD, and CAL were recorded at baseline before SRP. Only PI, EIBI, and GCCI were recorded at 1st and 2nd week. Twenty-one days post 2nd week, i.e., 6th week all the clinical parameters were recorded again. Results: Intragroup analysis of all the clinical parameters showed clinical significant results between baseline and 6th week. However, on intergroup analysis, the results were not significant. Conclusion: The local application of CoQ10 and hyaluronic acid gel in conjunction with SRP may have a beneficial effect on periodontal health in patients with chronic periodontitis. PMID:28298817

  18. Efficacy of single-dose hyaluronic acid products with two different structures in patients with early-stage knee osteoarthritis

    PubMed Central

    Dernek, Bahar; Duymus, Tahir Mutlu; Koseoglu, Pinar Kursuz; Aydin, Tugba; Kesiktas, Fatma Nur; Aksoy, Cihan; Mutlu, Serhat

    2016-01-01

    [Purpose] There are many types of hyaluronic acid preparations, but no clear data are available about which preparations is more effective. The aim of this trial was to investigate the effectiveness of different types of hyaluronic acid preparations on pain and function of inpatients with knee osteoarthritis. [Subjects and Methods] All patients were diagnosed by clinical examination and x-ray. Ostenil PLUS® was injected into 28 patients (group 1, 1.6 million daltons), and MONOVISC® (group 2, 2.5 million daltons) was injected into 46 patients. Demographic data and Western Ontario and McMaster Universities Osteoarthritis Index and Visual Analog Scale scores were used for clinical evaluation at 1, 3, and 6 months post injection. [Results] In both groups, baseline Ontario and McMaster Universities Osteoarthritis Index and Visual Analog Scale scores were higher compared with those in subsequent evaluations. Based on the pre- and post-injection data, a significant reduction in all scores was observed after the injections for in both groups. According to intergroup comparisons, there was no significant difference in any of the scores between the two groups. [Conclusion] There were no difference in Ontario and McMaster Universities Osteoarthritis Index and Visual Analog Scale scores in patients with knee osteoarthritis injected with two different hyaluronic acid structures in short-term preparations. PMID:27942115

  19. Intra-Articular Hyaluronic Acid Compared to Traditional Conservative Treatment in Dogs with Osteoarthritis Associated with Hip Dysplasia

    PubMed Central

    Carapeba, Gabriel O. L.; Cavaleti, Poliana; Brinholi, Rejane B.

    2016-01-01

    The purpose of this study was to compare the efficacy of the intra-articular (IA) hyaluronic acid injection to traditional conservative treatment (TCT) in dogs with osteoarthritis (OA) induced by hip dysplasia. Sixteen dogs were distributed into two groups: Hyal: IA injection of hyaluronic acid (5–10 mg), and Control: IA injection with saline solution (0.5–1.0 mL) in combination with a TCT using an oral nutraceutical (750–1000 mg every 12 h for 90 days) and carprofen (2.2 mg/kg every 12 h for 15 days). All dogs were assessed by a veterinarian on five occasions and the owner completed an assessment form (HCPI and CPBI) at the same time. The data were analyzed using unpaired t test, ANOVA, and Tukey's test (P < 0.05). Compared with baseline, lower scores were observed in both groups over the 90 days in the veterinarian evaluation, HCPI, and CPBI (P < 0.001). The Hyal group exhibited lower scores from 15 to 90 and 60 to 90 days, in the CBPI and in the veterinarian evaluation, respectively, compared to the Control group. Both treatments reduced the clinical signs associated with hip OA. However, more significant results were achieved with intra-articular hyaluronic acid injection. PMID:27847523

  20. Engineering S. equi subsp. zooepidemicus towards concurrent production of hyaluronic acid and chondroitin biopolymers of biomedical interest.

    PubMed

    Cimini, Donatella; Iacono, Ileana Dello; Carlino, Elisabetta; Finamore, Rosario; Restaino, Odile F; Diana, Paola; Bedini, Emiliano; Schiraldi, Chiara

    2017-12-01

    Glycosaminoglycans, such as hyaluronic acid and chondroitin sulphate, are not only more and more required as main ingredients in cosmeceutical and nutraceutical preparations, but also as active principles in medical devices and pharmaceutical products. However, while biotechnological production of hyaluronic acid is industrially established through fermentation of Streptococcus spp. and recently Bacillus subtilis, biotechnological chondroitin is not yet on the market. A non-hemolytic and hyaluronidase negative S. equi subsp. zooepidemicus mutant strain was engineered in this work by the addition of two E. coli K4 genes, namely kfoA and kfoC, involved in the biosynthesis of chondroitin-like polysaccharide. Chondroitin is the precursor of chondroitin sulphate, a nutraceutical present on the market as anti-arthritic drug, that is lately being studied for its intrinsic bioactivity. In small scale bioreactor batch experiments the production of about 1.46 ± 0.38 g/L hyaluronic acid and 300 ± 28 mg/L of chondroitin with an average molecular weight of 1750 and 25 kDa, respectively, was demonstrated, providing an approach to the concurrent production of both biopolymers in a single fermentation.

  1. Changes in the viscosity of hyaluronic acid after exposure to a myeloperoxidase-derived oxidant

    SciTech Connect

    Baker, M.S.; Green, S.P.; Lowther, D.A.

    1989-04-01

    Both purified hyaluronic acid (HA) and bovine synovial fluid react with OCI-, the major oxidant produced by the myeloperoxidase (MPO)/H/sub 2/O/sub 2//CI- system, resulting in a decrease in their specific viscosity. This reaction is inhibited in the presence of excess methionine. H/sub 2/O/sub 2/ alone decreases the viscosity of HA, presumably by the Fenton reaction, in the absence (but not in the presence) of the iron chelator, diethyltriaminepentacetic acid (DETAPAC). In the presence of DETAPAC, incubation of HA with the complete MPO/H/sub 2/O/sub 2//CI- system lowered the viscosity of HA. Analysis of 3H-HA exposed to OCI- by gel filtration chromatography indicated that cleavage of HA occurred only at higher OCI- concentrations. We suggest that the reduction in viscosity of HA by the MPO/H/sub 2/O/sub 2//CI- system may be due to a combination of oxidative cleavage and changes in the conformation of the molecule. We speculate that the changes in the molecular size of rheumatoid synovial fluid HA may be due to the action of the neutrophil MPO/H/sub 2/O/sub 2//CI- system.

  2. Hyaluronic Acid Modified Tantalum Oxide Nanoparticles Conjugating Doxorubicin for Targeted Cancer Theranostics.

    PubMed

    Jin, Yushen; Ma, Xibo; Feng, Shanshan; Liang, Xiao; Dai, Zhifei; Tian, Jie; Yue, Xiuli

    2015-12-16

    Theranostic tantalum oxide nanoparticles (TaOxNPs) of about 40 nm were successfully developed by conjugating functional molecules including polyethylene glycol (PEG), near-infrared (NIR) fluorescent dye, doxorubicin (DOX), and hyaluronic acid (HA) onto the surface of the nanoparticles (TaOx@Cy7-DOX-PEG-HA NPs) for actively targeting delivery, pH-responsive drug release, and NIR fluorescence/X-ray CT bimodal imaging. The obtained nanoagent exhibits good biocompatibility, high cumulative release rate in the acidic microenvironments, long blood circulation time, and superior tumor-targeting ability. Both in vitro and in vivo experiments show that it can serve as an excellent contrast agent to simultaneously enhance fluorescence imaging and CT imaging greatly. Most importantly, such a nanoagent could enhance the therapeutic efficacy of the tumor greatly and the tumor growth inhibition was evaluated to be 87.5%. In a word, multifunctional TaOx@Cy7-DOX-PEG-HA NPs can serve as a theranostic nanomedicine for fluorescence/X-ray CT bimodal imaging, remote-controlled therapeutics, enabling personalized detection, and treatment of cancer with high efficacy.

  3. Preliminary characterization of dexamethasone-loaded cross-linked hyaluronic acid films for topical ocular therapy.

    PubMed

    Calles, J A; López-García, A; Vallés, E M; Palma, S D; Diebold, Y

    2016-07-25

    The aim of this work was to design and characterize cross-linked hyaluronic acid (HA)-itaconic acid (IT) films loaded with dexamethasone sodium phosphate salt (DEX) for topical therapy of inflammatory ocular surface diseases. Films were chemically cross-linked with polyethylene glycol diglycidyl ether (PEGDE), then physical and mechanical characterization by stress-strain, X-ray diffraction, X-ray fluorescence spectrometry and swelling assays was conducted. A sequential in vitro therapeutic efficacy model was designed to assess changes in interleukin (IL)-6 production in an inflamed human corneal epithelial (HCE) cell line after film exposure. Changes in cell proliferation after film exposure were assessed using the alamarBlue(®) proliferation assay. Experimental findings showed desirable mechanical properties and in vitro efficacy to reduce cell inflammation. A moderately decreased proliferation rate was induced in HCE cells by DEX-loaded films, compared to commercial DEX eye drops. These results suggest that DEX and HA have opposite effects. The sequential in vitro therapeutic efficacy model arises as an efficient tool to study drug release from delivery systems by indirect measurement of a biological response.

  4. Emerging roles of hyaluronic acid bioscaffolds in tissue engineering and regenerative medicine.

    PubMed

    Hemshekhar, Mahadevappa; Thushara, Ram M; Chandranayaka, Siddaiah; Sherman, Larry S; Kemparaju, Kempaiah; Girish, Kesturu S

    2016-05-01

    Hyaluronic acid (HA), is a glycosaminoglycan comprised of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid. HA is synthesized by hyaluronan synthases and reaches sizes in excess of 2MDa. It plays numerous roles in normal tissues but also has been implicated in inflammatory processes, multiple drug resistance, angiogenesis, tumorigenesis, water homeostasis, and altered viscoelasticity of extracellular matrix. The physicochemical properties of HA including its solubility and the availability of reactive functional groups facilitate chemical modifications on HA, which makes it a biocompatible material for use in tissue regeneration. HA-based biomaterials and bioscaffolds do not trigger allergies or inflammation and are hydrophilic which make them popular as injectable dermal and soft tissue fillers. They are manufactured in different forms including hydrogels, tubes, sheets and meshes. Here, we review the pathophysiological and pharmacological properties and the clinical uses of native and modified HA. The review highlights the therapeutic applications of HA-based bioscaffolds in organ-specific tissue engineering and regenerative medicine.

  5. A comparison of molecular mass determination of hyaluronic acid using SEC/MALLS and sedimentation equilibrium.

    PubMed

    Hokputsa, Sanya; Jumel, Kornelia; Alexander, Catherine; Harding, Stephen E

    2003-08-01

    Hyaluronic acid (HA) is a natural polysaccharide with importance in the pharmaceutical, medical and cosmetic industries. Determining factors in its final applications are its physicochemical properties, particularly molecular mass. A high molecular mass HA was degraded using five different hydroxyl free-radical starting concentrations chemically produced from ascorbic acid and hydrogen peroxide. The aims of the study were to investigate the effect of different hydroxyl free-radical concentrations on the chain length of HA and compare the molecular masses obtained from analytical ultracentrifugation using sedimentation equilibrium experiments and size exclusion chromatography/multi-angle laser light scattering (SEC/MALLS). The results indicated that their molecular masses varied, depending on the degree of hydroxyl free-radical starting concentration. Molecular mass values obtained from sedimentation equilibrium experiments for each sample showed the same trend as those obtained from the SEC/MALLS in the range of molecular masses studied. The molecular masses obtained from sedimentation equilibrium for high molecular mass samples from reciprocal plots of apparent weight average molecular mass against concentration gave values similar to those obtained by SEC/MALLS. In contrast, the molecular mass from conventional plots for high molecular mass samples were much lower than those from SEC/MALLS, even when high ionic strength buffers were used.

  6. Expression of hyaluronan (hyaluronic acid) in the developing laminar architecture of the human fetal brain.

    PubMed

    Shibata, Shunichi; Cho, Kwang Ho; Kim, Ji Hyun; Abe, Hiroshi; Murakami, Gen; Cho, Baik Hwan

    2013-10-01

    Hyaluronan (also called hyaluronic acid or HA) plays a key role in the morphogenesis of the brain, but little is known about its expression in the human fetal neocortex. Using immunohistochemical methods, we assayed the expression of HA, glial fibrillary acidic protein, vimentin, nestin, and proliferating cell nuclear antigen in paraffin-embedded histologic sections of 8 mid-term fetuses (estimated gestational age, 12-16 weeks; crown-rump length, 75-120mm). At 12-13 weeks, HA was expressed strongly along the membranes of many cells in the cortical plate and the layer 1 or marginal zone, but showed weak, spotty expression in a fiber-rich layer adjacent to the cortical plate, called the cortical stratified transitional field-1 (STF-1 or a primitive form of the subplate). At 15-16 weeks, HA was expressed in the layer 1 and in the early subplate or presubplate, but less strongly in cells of the possible STF-5 near the subventricular zone. However, the positive observation in STF-5 was probably a result of individual difference in development. The developing cortical plate seemed to produce HA in the presubplate to harbor axonal plexus of various afferent systems, while Cajal-Retzius cells were likely to accumulate HA in the layer 1. The HA-rich zones, those sandwiched the cortical plate, might avoid further migration of cortical cells.

  7. Design of Hyaluronic Acid Hydrogels to Promote Neurite Outgrowth in Three Dimensions.

    PubMed

    Tarus, Dominte; Hamard, Lauriane; Caraguel, Flavien; Wion, Didier; Szarpak-Jankowska, Anna; van der Sanden, Boudewijn; Auzély-Velty, Rachel

    2016-09-28

    A hyaluronic acid (HA)-based extracellular matrix (ECM) platform with independently tunable stiffness and density of cell-adhesive peptide (RGD, arginine-glycine-aspartic acid) that mimics key biochemical and mechanical features of brain matrix has been designed. We demonstrated here its utility in elucidating ECM regulation of neural progenitor cell behavior and neurite outgrowth. The analysis of neurite outgrowth in 3-D by two-photon microscopy showed several important results in the development of these hydrogels. First, the ability of neurites to extend deeply into these soft HA-based matrices even in the absence of cell-adhesive ligand further confirms the potential of HA hydrogels for central nervous system (CNS) regeneration. Second, the behavior of hippocampal neural progenitor cells differed markedly between the hydrogels with a storage modulus of 400 Pa and those with a modulus of 800 Pa. We observed an increased outgrowth and density of neurites in the softest hydrogels (G' = 400 Pa). Interestingly, cells seeded on the surface of the hydrogels functionalized with the RGD ligand experienced an optimum in neurite outgrowth as a function of ligand density. Surprinsingly, neurites preferentially progressed inside the gels in a vertical direction, suggesting that outgrowth is directed by the hydrogel structure. This work may provide design principles for the development of hydrogels to facilitate neuronal regeneration in the adult brain.

  8. In situ supramolecular hydrogel based on hyaluronic acid and dextran derivatives as cell scaffold.

    PubMed

    Chen, Jing-Xiao; Cao, Lu-Juan; Shi, Yu; Wang, Ping; Chen, Jing-Hua

    2016-09-01

    In this study, hyaluronic acid-β-cyclodextrin conjugate (HA-CD) and dextran-2-naphthylacetic acid conjugate (Dex-NAA) were synthesized as two gelators. The degrees of substitution (DS) of these two gelators were determined to be 15.5 and 7.4%, respectively. Taking advantages of the strong and selective host-guest interaction between β-CD and 2-NAA, the mixture of two gelators could form supramolecular hydrogel in situ. Moreover, the pore size, gelation time, swelling ratio as well as modulus of the hydrogel could be adjusted by simply varying the contents of HA-CD and Dex-NAA. NIH/3T3 cells that entrapped in hydrogel grew well as compared with that cultured in plates, indicating a favorable cytocompatibility of the hydrogel. Collectively, the results demonstrated that the HA-Dex hydrogel could potentially be applied in tissue engineering as cell scaffold. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2263-2270, 2016.

  9. Nanostructured polymeric coatings based on chitosan and dopamine-modified hyaluronic acid for biomedical applications.

    PubMed

    Neto, Ana I; Cibrão, Ana C; Correia, Clara R; Carvalho, Rita R; Luz, Gisela M; Ferrer, Gloria G; Botelho, Gabriela; Picart, Catherine; Alves, Natália M; Mano, João F

    2014-06-25

    In a marine environment, specific proteins are secreted by mussels and used as a bioglue to stick to a surface. These mussel proteins present an unusual amino acid 3,4-dihydroxyphenylalanine (known as DOPA). The outstanding adhesive properties of these materials in the sea harsh conditions have been attributed to the presence of the catechol groups present in DOPA. Inspired by the structure and composition of these adhesive proteins, dopamine-modified hyaluronic acid (HA-DN) prepared by carbodiimide chemistry is used to form thin and surface-adherent dopamine films. This conjugate was characterized by distinct techniques, such as nuclear magnetic resonance and ultraviolet spectrophotometry. Multilayer films are developed based on chitosan and HA-DN to form polymeric coatings using the layer-by-layer methodology. The nanostructured films formation is monitored by quartz crystal microbalance. The film surface is characterized by atomic force microscopy and scanning electron microscopy. Water contact angle measurements are also conducted. The adhesion properties are analyzed showing that the nanostructured films with dopamine promote an improved adhesion. In vitro tests show an enhanced cell adhesion, proliferation and viability for the biomimetic films with catechol groups, demonstrating their potential to be used in distinct biomedical applications.

  10. A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

    NASA Astrophysics Data System (ADS)

    Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

    2016-11-01

    Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.

  11. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    PubMed Central

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-01-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi–HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi–HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery. PMID:25074521

  12. A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

    PubMed Central

    Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

    2016-01-01

    Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications. PMID:27901092

  13. Iodinated hyaluronic acid oligomer-based nanoassemblies for tumor-targeted drug delivery and cancer imaging.

    PubMed

    Lee, Jae-Young; Chung, Suk-Jae; Cho, Hyun-Jong; Kim, Dae-Duk

    2016-04-01

    Nano-sized self-assemblies based on amphiphilic iodinated hyaluronic acid (HA) were developed for use in cancer diagnosis and therapy. 2,3,5-Triiodobenzoic acid (TIBA) was conjugated to an HA oligomer as a computed tomography (CT) imaging modality and a hydrophobic residue. Nanoassembly based on HA-TIBA was fabricated for tumor-targeted delivery of doxorubicin (DOX). Cellular uptake of DOX from nanoassembly, compared to a DOX solution group, was enhanced via an HA-CD44 receptor interaction, and subsequently, the in vitro antitumor efficacy of DOX-loaded nanoassembly was improved in SCC7 (CD44 receptor positive squamous cell carcinoma) cells. Cy5.5, a near-infrared fluorescence (NIRF) dye, was attached to the HA-TIBA conjugate and the in vivo tumor targetability of HA-TIBA nanoassembly, which is based on the interaction between HA and CD44 receptor, was demonstrated in a NIRF imaging study using an SCC7 tumor-xenografted mouse model. Tumor targeting and cancer diagnosis with HA-TIBA nanoassembly were verified in a CT imaging study using the SCC7 tumor-xenografted mouse model. In addition to efficient cancer diagnosis using NIRF and CT imaging modalities, improved antitumor efficacies were shown. HA and TIBA can be used to produce HA-TIBA nanoassembly that may be a promising theranostic nanosystem for cancers that express the CD44 receptor.

  14. Hyaluronic acid as an internal wetting agent in model DMAA/TRIS contact lenses.

    PubMed

    Weeks, Andrea; Luensmann, Doerte; Boone, Adrienne; Jones, Lyndon; Sheardown, Heather

    2012-11-01

    Model silicone hydrogel contact lenses, comprised of N,N-dimethylacrylamide and methacryloxypropyltris (trimethylsiloxy) silane, were fabricated and hyaluronic acid (HA) was incorporated as an internal wetting agent using a dendrimer-based method. HA and dendrimers were loaded into the silicone hydrogels and cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. The presence and location of HA in the hydrogels was confirmed using X-ray photoelectron spectroscopy and confocal laser scanning microscopy, respectively. The effects of the presence of HA on the silicone hydrogels on hydrophilicity, swelling behavior, transparency, and lysozyme sorption and denaturation were evaluated. The results showed that HA increased the hydrophilicity and the equilibrium water content of the hydrogels without affecting transparency. HA also significantly decreased the amount of lysozyme sorption (p < 0.002). HA had no effect on lysozyme denaturation in hydrogels containing 0% and 1.7% methacrylic acid (MAA) (by weight) but when the amount of MAA was increased to 5%, the level of lysozyme denaturation was significantly lower compared to control materials. These results suggest that HA has great potential to be used as a wetting agent in silicone hydrogel contact lenses to improve wettability and to decrease lysozyme sorption and denaturation.

  15. Hyaluronic acid-modified multiwalled carbon nanotubes for targeted delivery of doxorubicin into cancer cells.

    PubMed

    Cao, Xueyan; Tao, Lei; Wen, Shihui; Hou, Wenxiu; Shi, Xiangyang

    2015-03-20

    Development of novel drug carriers for targeted cancer therapy with high efficiency and specificity is of paramount importance and has been one of the major topics in current nanomedicine. Here we report a general approach to using multifunctional multiwalled carbon nanotubes (MWCNTs) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, polyethyleneimine (PEI)-modified MWCNTs were covalently conjugated with fluorescein isothiocyanate (FI) and hyaluronic acid (HA). The formed MWCNT/PEI-FI-HA conjugates were characterized via different techniques and were used as a new carrier system to encapsulate the anticancer drug doxorubicin for targeted delivery to cancer cells overexpressing CD44 receptors. We show that the formed MWCNT/PEI-FI-HA/DOX complexes with a drug loading percentage of 72% are water soluble and stable. In vitro release studies show that the drug release rate under an acidic condition (pH 5.8, tumor cell microenvironment) is higher than that under physiological condition (pH 7.4). Cell viability assay demonstrates that the carrier material has good biocompatibility in the tested concentration range, and the MWCNT/PEI-FI-HA/DOX complexes can specifically target cancer cells overexpressing CD44 receptors and exert growth inhibition effect to the cancer cells. The developed HA-modified MWCNTs hold a great promise to be used as an efficient anticancer drug carrier for tumor-targeted chemotherapy.

  16. Spontaneous arrangement of a tumor targeting hyaluronic acid shell on irinotecan loaded PLGA nanoparticles.

    PubMed

    Giarra, Simona; Serri, Carla; Russo, Luisa; Zeppetelli, Stefania; De Rosa, Giuseppe; Borzacchiello, Assunta; Biondi, Marco; Ambrosio, Luigi; Mayol, Laura

    2016-04-20

    The arrangement of tumor targeting hyaluronic acid (HA) moieties on irinotecan (IRIN)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) has been directed by means of a gradient of lipophilicity between the oil and water phases of the emulsion used to produce the NPs. PLGA constitutes the NP bulk while HA is superficially exposed, with amphiphilic poloxamers acting as a bridge between PLGA and HA. Differential scanning calorimetry, zeta potential analyses and ELISA tests were employed to support the hypothesis of polymer assembly in NP formulations. The presence of flexible HA chains on NP surface enhances NP size stability over time due to an increased electrostatic repulsion between NPs and a higher degree of hydration of the device surface. IRIN in vitro release kinetics can be sustained up to 7-13 days. In vitro biologic studies indicated that HA-containing NPs were more toxic than bare PLGA NPs against CD44-overexpressing breast carcinoma cells (HS578T), therefore indicating their ability to target CD44 receptor.

  17. Antisense oligodeoxynucleotide-conjugated hyaluronic acid/protamine nanocomplexes for intracellular gene inhibition.

    PubMed

    Mok, Hyejung; Park, Ji Won; Park, Tae Gwan

    2007-01-01

    Green fluorescent protein (GFP) antisense oligodeoxynucleotide (ODN) was covalently conjugated to hyaluronic acid (HA) via a reducible disulfide linkage, and the HA-ODN conjugate was complexed with protamine to increase the extent of cellular uptake and enhance the gene inhibition efficiency of GFP expression. The HA-ODN conjugate formed more stable polyelectrolyte complexes with protamine as compared to naked ODN, probably because of its increased charge density. The higher cellular uptake of protamine/HA-ODN complexes than that of protamine/naked ODN complexes was attributed to the formation of more compact nanosized complexes (approximately 200 nm in diameter) in aqueous solution. Protamine/HA-ODN complexes also showed a comparable level of GFP gene inhibition to that of cytotoxic polyethylenimine (PEI)/ODN complexes. Since both HA and protamine are naturally occurring biocompatible materials, the current formulation based on a cleavable conjugation strategy of ODN to HA could be potentially applied as safe and effective nonviral carriers for ODN and siRNA nucleic acid therapeutics.

  18. Selective binding of C-6 OH sulfated hyaluronic acid to the angiogenic isoform of VEGF(165).

    PubMed

    Lim, Dong-Kwon; Wylie, Ryan G; Langer, Robert; Kohane, Daniel S

    2016-01-01

    Vascular endothelial growth factor 165 (VEGF165) is an important extracellular protein involved in pathological angiogenesis in diseases such as cancer, wet age-related macular degeneration (wet-AMD) and retinitis pigmentosa. VEGF165 exists in two different isoforms: the angiogenic VEGF165a, and the anti-angiogenic VEGF165b. In some angiogenic diseases the proportion of VEGF165b may be equal to or higher than that of VEGF165a. Therefore, developing therapeutics that inhibit VEGF165a and not VEGF165b may result in greater anti-angiogenic activity and therapeutic benefit. To this end, we report the selective binding properties of sulfated hyaluronic acid (s-HA). Selective biopolymers offer several advantages over antibodies or aptamers including cost effective and simple synthesis, and the ability to make nanoparticles or hydrogels for drug delivery applications or VEGF165a sequestration. Limiting sulfation to the C-6 hydroxyl (C-6 OH) in the N-acetyl-glucosamine repeat unit of hyaluronic acid (HA) resulted in a polymer with strong affinity for VEGF165a but not VEGF165b. Increased sulfation beyond the C-6 OH (i.e. greater than 1 sulfate group per HA repeat unit) resulted in s-HA polymers that bound both VEGF165a and VEGF165b. The C-6 OH sulfated HA (Mw 150 kDa) showed strong binding properties to VEGF165a with a fast association rate constant (Ka; 2.8 × 10(6) M(-1) s(-1)), slow dissociation rate constant (Kd; 2.8 × 10(-3) s(-1)) and strong equilibrium binding constant (KD; ∼1.0 nM)), which is comparable to the non-selective VEGF165 binding properties of the commercialized therapeutic anti-VEGF antibody (Avastin(®)). The C-6 OH sulfated HA also inhibited human umbilical vein endothelial cell (HUVEC) survival and proliferation and human dermal microvascular endothelial cell (HMVEC) tube formation. These results demonstrate that the semi-synthetic natural polymer, C-6 OH sulfated HA, may be a promising biomaterial for the treatment of angiogenesis

  19. Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.

    PubMed

    Liu, Kai; Wang, Zhi-qi; Wang, Shi-jiang; Liu, Ping; Qin, Yue-hong; Ma, Yan; Li, Xiao-Chen; Huo, Zhi-Jun

    2015-01-01

    Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer

  20. Hyaluronic acid (Supartz®): a review of its use in osteoarthritis of the knee.

    PubMed

    Curran, Monique P

    2010-11-01

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

  1. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    PubMed Central

    Wei, Wen-Hao; Dong, Xue-Meng; Liu, Chen-Guang

    2015-01-01

    Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy. PMID:25837468

  2. In vitro investigation of self-assembled nanoparticles based on hyaluronic acid-deoxycholic acid conjugates for controlled release doxorubicin: effect of degree of substitution of deoxycholic acid.

    PubMed

    Wei, Wen-Hao; Dong, Xue-Meng; Liu, Chen-Guang

    2015-03-31

    Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin-mediated cancer therapy.

  3. Comparison of the Hyaluronic Acid Vaginal Cream and Conjugated Estrogen Used in Treatment of Vaginal Atrophy of Menopause Women: A Randomized Controlled Clinical Trial

    PubMed Central

    Jokar, Azam; Davari, Tayebe; Asadi, Nasrin; Ahmadi, Fateme; Foruhari, Sedighe

    2016-01-01

    Background: Vaginal atrophy is a common complication in menopause which does not improve with time and, if untreated, can affect the quality of life for women. The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen (Premarin) in treatment of vaginal atrophy. Methods: This study was a randomized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy; they were randomly allocated to two groups (recipient conjugated estrogen and hyaluronic acid). The severity of each sign of atrophy was evaluated by visual analog signals (VAS) and on the basis of a four point scale. Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0-100. As to the vaginal PH, we used PH marker band, the rate of which was divided into 4 degrees. Data were analyzed using SPSS, version 20, and P≤0.05 was considered as significant. Results: The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups. Dryness, itching, maturation index, PH and composite score of the vaginal symptoms were relieved significantly in both groups (P<0.001). Dyspareunia in Premarin (P<0.05) and hyaluronic acid (P<0.001) decreased compared with pre-treatment. Urinary incontinence only showed improvement in the hyaluronic acid group (P<0.05). Improvement in urinary incontinence, dryness, maturation index (P<0.05) and composite score of vaginal symptoms (P<0.001) in the hyaluronic acid group was better than those in the Premarin group. Conclusion: According to the results of the present study, hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy. But hyaluronic acid was more effective and this drug is suggested for those who do not want to or cannot take local hormone treatment. Trial Registration Number: IRCT2013022712644N1 PMID:26793732

  4. Consensus statement on viscosupplementation with hyaluronic acid for the management of osteoarthritis.

    PubMed

    Henrotin, Yves; Raman, Raghu; Richette, Pascal; Bard, Hervé; Jerosch, Jörg; Conrozier, Thierry; Chevalier, Xavier; Migliore, Alberto

    2015-10-01

    Viscosupplementation (VS) with hyaluronic acid is currently used by physicians to treat osteoarthritis. However, many aspects of this treatment remain questionable and subject of controversy. A group of 8 experts in this field, from European countries, met to debate on 24 statements previously listed by the group members. Based on an extensive research of the literature and expert opinion, a consensus position has been proposed for each statement. Agreement was achieved on some recommendations. In particular, the expert achieved unanimous agreement in favor of the following statements: VS is an effective treatment for mild to moderate knee OA; VS is not an alternative to surgery in advanced hip OA; VS is a well-tolerated treatment of knee and other joints OA; VS should not be used only in patients who have failed to respond adequately to analgesics and NSAIDs; VS is a "positive" indication but not a "lack of anything better" indication; the dosing regimen must be supported by evidence-based medicine; cross-linking is a proven means for prolonging IA residence time of HA; the best approach to inject accurately knee joint is the lateral mid-patellar one; when VS is performed under fluoroscopy, the amount of radiopaque contrast agent must be as low as possible to avoid viscosupplement dilution. These clear recommendations have been established to help practitioners in the use of viscosupplementation.

  5. Tough and elastic hydrogel of hyaluronic acid and chondroitin sulfate as potential cell scaffold materials.

    PubMed

    Ni, Yilu; Tang, Zhurong; Cao, Wanxu; Lin, Hai; Fan, Yujiang; Guo, Likun; Zhang, Xingdong

    2015-03-01

    Natural polysaccharides are extensively investigated as cell scaffold materials for cellular adhesion, proliferation, and differentiation due to their excellent biocompatibility, biodegradability, and biofunctions. However, their application is often severely limited by their mechanical behavior. In this study, a tough and elastic hydrogel scaffold was prepared with hyaluronic acid (HA) and chondroitin sulfate (CS). HA and CS were conjugated with tyramine (TA) and the degree of substitution (DS) was 10.7% and 11.3%, respectively, as calculated by (1)H NMR spectra. The hydrogel was prepared by mixing HA-TA and CS-TA in presence of H2O2 and HRP. The sectional morphology of hydrogels was observed by SEM, static and dynamic mechanical properties were analyzed by Shimadzu electromechanical testing machine and dynamic mechanical thermal analyzer Q800. All samples showed good ability to recover their appearances after deformation, the storage modulus (E') of hydrogels became higher as the testing frequency went up. Hydrogels also showed fatigue resistance to cyclic compression. Mesenchymal stem cells encapsulated in hydrogels showed good cell viability as detected by CLSM. This study suggests that the hydrogels have both good mechanical properties and biocompatibility, and may serve as model systems to explore mechanisms of deformation and energy dissipation or find some applications in tissue engineering.

  6. Hyaluronic acid delays boar sperm capacitation after 3 days of storage at 15 degrees C.

    PubMed

    Yeste, M; Briz, M; Pinart, E; Sancho, S; Garcia-Gil, N; Badia, E; Bassols, J; Pruneda, A; Bussalleu, E; Casas, I; Bonet, S

    2008-12-01

    The present study was undertaken to determine the effects of the addition of hyaluronic acid (HA), ranged from 12.5 to 200 microg/ml, on boar sperm capacitation status during a storage time (up to 3 days) at 15 degrees C in Beltsville thawing solution (BTS). The raw extender was the negative control whereas different concentrations of caffeine (CAF), ranged from 0.25 to 8mM, served as positive controls. Sperm viability, motility, morphology, and osmotic resistance were also determined before and after assessing the treatments. Samples were obtained from 28 healthy and post-pubertal Piétrain boars and sperm parameters were tested immediately after the addition of treatments and after 1, 2 and 3 days of refrigeration at 15 degrees C. Sperm capacitation status was determined by chlortetracycline (CTC) staining and sperm viability by means of a multiple fluorochrome-staining test. Sperm motility and morphology were assessed using phase-contrast microscopy accompanied by a computer assisted sperm analysis system (CASA). Whereas HA delayed sperm capacitation, CAF increased the frequency of capacitated spermatozoa after 2 days of cooling. Moreover, HA did not modify other sperm parameters, such as sperm velocity, whereas CAF increased progressive motility during the first 2 days of cooling and then decreased. It can be concluded that the addition of HA at 50 and 100 microg/ml to the BTS extender may delay sperm capacitation after 3 days of cooling.

  7. Photosensitizer-Conjugated Hyaluronic Acid-Shielded Polydopamine Nanoparticles for Targeted Photomediated Tumor Therapy.

    PubMed

    Han, Jieun; Park, Wooram; Park, Sin-Jung; Na, Kun

    2016-03-01

    Photodynamic therapy (PDT) is a widely used clinical option for tumor therapy. However, the clinical utilization of conventional small-molecule photosensitizers (PSs) for PDT has been limited by their low selectivity for disease sites, and undesirable photoactivation. To overcome these limitations, we demonstrated a tumor-specific and photoactivity-controllable nanoparticle photomedicine based on a combination of PS-biomacromolecule conjugates and polydopamine nanoparticles (PD-NP) for an effective tumor therapy. This novel photomedicine consisted of a PD-NP core and a PS-conjugated hyaluronic acid (PS-HA) shell. The PD-NP and the PS-HA play roles as a quencher for PSs and a cancer targeting moiety, respectively. The synthesized PS-HA-shielded PD-NPs (PHPD-NPs) had a relatively narrow size distribution (approximately 130 nm) with uniform spherical shapes. In response to cancer-specific intracellular enzymes (e.g., hyaluronidase), the PHPD-NPs exhibited an excellent singlet oxygen generation capacity for PDT. Furthermore, an efficient photothermal conversion ability for photothermal therapy (PTT) was also shown in the PHPD-NPs system. These properties provide superior therapeutic efficacy against cancer cells. In mice tumor model, the photoactive restorative effects of the PHPD-NPs were much higher in cancer microenvironments compared to that in the normal tissue. As a result, the PHPD-NPs showed a significant antitumor activity in in vivo mice tumor model. The nanoparticle photomedicine design is a novel strategy for effective tumor therapy.

  8. Proteomic Profiling of Neuroblastoma Cells Adhesion on Hyaluronic Acid-Based Surface for Neural Tissue Engineering

    PubMed Central

    Chen, Ko-Chin; Chiang, Pei-Wen; Chu, Pei-Yu; Lu, Yi-Shan; Yuan, Cheng-Hui; Wang, Ming-Chen; Lin, Chia-Yang; Huang, Ying-Fong; Jong, Shiang-Bin; Lin, Po-Chiao

    2016-01-01

    The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application. PMID:28053978

  9. The effect of hyaluronic acid on biofunctionality of gelatin-collagen intestine tissue engineering scaffolds.

    PubMed

    Shabafrooz, Vahid; Mozafari, Masoud; Köhler, Gerwald A; Assefa, Senait; Vashaee, Daryoosh; Tayebi, Lobat

    2014-09-01

    The creation of engineered intestinal tissue has recently stimulated new endeavors with the ultimate goal of intestinal replacement for massive resections of bowel. In this context, we investigated the effect of hyaluronic acid (HA) on the physicochemical characteristics of gelatin-collagen scaffolds and its cytocompatibilty to the human intestinal epithelial Caco-2 cell line in vitro. Gelatin/collagen hybrid scaffolds with different concentrations of HA were prepared by solvent casting and freeze-drying techniques and subsequent chemical crosslinking by genipin. The morphologies of the scaffolds were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. In vitro tests were carried out in phosphate-buffered saline (PBS) solution to study the swelling ratio and the biostability of the scaffolds. It was found that the porous structure of the scaffolds could be tailored by further addition of HA. Moreover, both the swelling ratio and the degradation rate of the scaffold increased by addition of HA. A resazurin-based cell viability assay was employed to determine the viability and estimate the number of scaffold-adherent Caco-2 cells. The assay indicated that the scaffolds were all cytocompatible. We concluded that addition of less than 15% HA to scaffolds with a composition of 9:1 gelatin:collagen results only in incremental improvement in the structural characteristics and cytocompatibility of the gelatin-collagen scaffolds. However, the scaffolds with 25% HA exhibited remarkable enhancement in physicochemical characteristics of the scaffolds including cell viability, growth, and attachment as well as their physical structure.

  10. The influence of mineral ions on the microbial production and molecular weight of hyaluronic acid.

    PubMed

    Pires, Aline Mara B; Eguchi, Silvia Y; Santana, Maria Helena Andrade

    2010-12-01

    This study aimed to evaluate the influence of the culture medium supplementation with mineral ions, focusing on the growth of Streptococcus zooepidemicus as well as on the production and average molecular weight (MW) of hyaluronic acid (HA). The ions were investigated in terms of individual absence from the totally supplemented medium (C+) or individual presence in the non-supplemented medium (C-), where C+ and C- were used as controls. Differences between the effects were analyzed using the Tukey's test at p < 0.05. The adopted criteria considered required the ions, whose individual absence attained at 80% or less of the C+ and their individual presence was 20% or more than the C-. The supplementation was either inhibitory or acted in synergy with other ions, when the individual absence or presence was 20% higher than C+ or 20% lower than C-, respectively. Results showed that the effects of C+ or C- were equal for both the production of HA and its yield from glucose. However, C+ showed to be beneficial to cell growth while the individual absence of Na+ was beneficial to the production of HA. The highest MW of HA (7.4 x 10⁷ Da) was observed in the individual presence of Na+ in spite of the lowest HA concentration (0.65 g x L⁻¹). These results suggest that the quality of HA can be modulated through the mineral ion supplementation.

  11. A novel coculture model of HUVECs and HUASMCs by hyaluronic acid micropattern on titanium surface.

    PubMed

    Li, Jingan; Zhang, Kun; Xu, Ying; Chen, Jiang; Yang, Ping; Zhao, Yuancong; Zhao, Ansha; Huang, Nan

    2014-06-01

    Orientation smooth muscle cell environment plays a positive role in the development of a functional, adherent endothelium. Therefore, building an orientation coculture model of endothelial cells (ECs) and smooth muscle cells (SMCs) on biomaterials surface may provide more help for understanding the interaction between the two cells in vitro. In the present study, a "SMCs-ColIV-ECs" coculture model was built on the hyaluronic acid (HA) patterned titanium (Ti) surface, and compared with the previous "SMCs-HAa-ECs" model on endothelial cell number, morphology index, nitric oxide (NO), and prostacyclin2 (PGI2) release, anticoagulation property, human umbilical artery smooth muscle cells (HUASMCs) inhibition property and retention under fluid flow shear stress. The result indicated that "SMCs-ColIV-ECs" model could enhance the number, spreading area, and major/minor index of human umbilical vein endothelial cells (HUVECs), which contributed to the retention of HUVECs on the surface. Greater major/minor index may produce more NO and PGI2 release, contributing to the anticoagulation property and HUASMCs inhibition property. In summary, this novel "SMCs-ColIV-ECs" coculture model improved the previous "SMCs-HAa-ECs" model, and may provide more inspiration for the human vascular intima building on the biomaterials in vitro.

  12. Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model.

    PubMed

    Tokatlian, Talar; Cam, Cynthia; Segura, Tatiana

    2015-05-01

    The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect. Here, 100 and 60 μm porous and nonporous (n-pore) hyaluronic acid-MMP hydrogels with encapsulated reporter (pGFPluc) or proangiogenic (pVEGF) plasmids are used to investigate scaffold-mediated gene delivery for local gene therapy in a diabetic wound healing mouse model. Porous hydrogels allow for significantly faster wound closure compared with n-pore hydrogels, which do not degrade and essentially provide a mechanical barrier to closure. Interestingly, the delivery of pDNA/PEI polyplexes positively promotes granulation tissue formation even when the DNA does not encode for an angiogenic protein. And although transfected cells are present throughout the granulation tissue surrounding, all hydrogels at 2 weeks, pVEGF delivery does not further enhance the angiogenic response. Despite this, the presence of transfected cells shows promise for the use of polyplex-loaded porous hydrogels for local gene delivery in the treatment of diabetic wounds.

  13. Viscoelasticity of hyaluronic acid-gelatin hydrogels for vocal fold tissue engineering.

    PubMed

    Kazemirad, Siavash; Heris, Hossein K; Mongeau, Luc

    2016-02-01

    Crosslinked injectable hyaluronic acid (HA)-gelatin (Ge) hydrogels have remarkable viscoelastic and biological properties for vocal fold tissue engineering. Patient-specific tuning of the viscoelastic properties of this injectable biomaterial could improve tissue regeneration. The frequency-dependent viscoelasticity of crosslinked HA-Ge hydrogels was measured as a function of the concentration of HA, Ge, and crosslinker. Synthetic extracellular matrix hydrogels were fabricated using thiol-modified HA and Ge, and crosslinked by poly(ethylene glycol) diacrylate. A recently developed characterization method based on Rayleigh wave propagation was used to quantify the frequency-dependent viscoelastic properties of these hydrogels, including shear storage and loss moduli, over a broad frequency range; that is, from 40 to 4000 Hz. The viscoelastic properties of the hydrogels increased with frequency. The storage and loss moduli values and the rate of increase with frequency varied with the concentrations of the constituents. The range of the viscoelastic properties of the hydrogels was within that of human vocal fold tissue obtained from in vivo and ex vivo measurements. Frequency-dependent parametric relations were obtained using a linear least-squares regression. The results are useful to better fine-tune the storage and loss moduli of HA-Ge hydrogels by varying the concentrations of the constituents for use in patient-specific treatments.

  14. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

    PubMed

    Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

    2017-01-28

    Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC.

  15. Hyaluronic Acid Hydrogels Support Cord-Like Structures from Endothelial Colony-Forming Cells

    PubMed Central

    Yee, Derek; Hanjaya-Putra, Donny; Bose, Vivek; Luong, Eli

    2011-01-01

    The generation of functional vascular networks has the potential to improve treatment for vascular diseases and to facilitate successful organ transplantation. Endothelial colony-forming cells (ECFCs) have robust proliferative potential and can form vascular networks in vivo. ECFCs are recruited from a bone marrow niche to the site of vascularization, where cues from the extracellular matrix instigate vascular morphogenesis. Although this process has been elucidated using natural matrix, little is known about vascular morphogenesis by ECFCs in synthetic matrix, a xeno-free scaffold that can provide a more controllable and clinically relevant alternative for regenerative medicine. We sought to study hyaluronic acid (HA) hydrogels as three-dimensional scaffolds for capillary-like structure formation from ECFCs, and to determine the crucial parameters needed to design such synthetic scaffolds. We found that ECFCs express HA-specific receptors and that vascular endothelial growth factor stimulates hyaluronidase expression in ECFCs. Using a well-defined and controllable three-dimensional HA culture system, we were able to decouple the effect of matrix viscoelasticity from changes in adhesion peptide density. We determined that decreasing matrix viscoelasticity, which corresponds to a loose ultrastructure, significantly increases ECFC vascular tube length and area, and that the effect of local delivery of vascular endothelial growth factor within the hydrogel depends on the makeup of the synthetic environment. Collectively, these results set forth initial design criteria that need to be considered in developing vascularized tissue constructs. PMID:21247340

  16. Topical Delivery of Hyaluronic Acid into Skin using SPACE-peptide Carriers

    PubMed Central

    Chen, Ming; Gupta, Vivek; Anselmo, Aaron C.; Muraski, John A.; Mitragotri, Samir

    2014-01-01

    Topical penetration of macromolecules into skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200–325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (~110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/−1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into skin. PMID:24129342

  17. Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

    PubMed Central

    Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

    2016-01-01

    Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

  18. Investigation of Overrun-Processed Porous Hyaluronic Acid Carriers in Corneal Endothelial Tissue Engineering

    PubMed Central

    Lai, Jui-Yang; Cheng, Hsiao-Yun; Ma, David Hui-Kang

    2015-01-01

    Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function. PMID:26296087

  19. Hyaluronic acid binding, endocytosis and degradation by sinusoidal liver endothelial cells

    SciTech Connect

    McGary, C.T.

    1988-01-01

    The binding, endocytosis, and degradation of {sup 125}I-hyaluronic acid ({sup 125}I-HA) by liver endothelial cells (LEC) was studied under several conditions. The dissociation of receptor-bound {sup 125}I-HA was rapid, with a half time of {approx}31 min and a K{sub off} of 6.3 {times} 10{sup {minus}4}/sec. A large reversible increase in {sup 125}I-HA binding to LEC at pH 5.0 was due to an increase in the observed affinity of the binding interaction. Pronase digestion suggested the protein nature of the receptor and the intracellular location of the digitonin exposed binding activity. Binding and endocytosis occur in the presence of 10 mM EGTA indicating that divalent cations are not required for receptor function. To study the degradation of {sup 125}I-HA by LEC, a cetylpyridinium chloride (CPC) precipitation assay was characterized. The minimum HA length required for precipitation was elucidated. The fate of the LEC HA receptor after endocytosis was examined.

  20. Expression and purification of RHC-EGFP fusion protein and its application in hyaluronic acid assay.

    PubMed

    Duan, Ningjun; Lv, Wansheng; Zhu, Lingli; Zheng, Weijuan; Hua, Zichun

    2017-03-16

    Hyaluronan is a widely distributed glycosaminoglycan which has multiple functions. Hyaluronic acid (HA) accumulation has been reported in many human diseases. Understanding the role of hyaluronan and its binding proteins in the pathobiology of disease will facilitate the development of novel therapeutics for many critical diseases. Current techniques described for the analysis of HA are mainly for HA quantification in solutions, not for the direct detection of HA in tissues or on cell surfaces. In our study, a fusion protein, named C-terminal domain of RHAMM-enhanced green fluorescence protein (RHC-EGFP), combined the HA-binding domain, C-terminal of receptor for hyaluronan-mediated motility, with EGFP, a widely used enhanced green fluorescence protein, was expressed and purified from Escherichia coli with high purity. Based on the sensitivity and convenience of fluorescence detection, methods for direct assay of HA in solutions, on cell surface or in tissues were established using RHC-EGFP. The binding specificity was also confirmed by competitive binding experiment and hyaluronidase degradation experiment. Our results provide an alternative choice for the specific and convenient assay of HA in various samples, and maybe helpful for further understanding of the fundamental and comprehensive functions of HA.

  1. Self assembled hyaluronic acid nanoparticles as a potential carrier for targeting the inflamed intestinal mucosa.

    PubMed

    Vafaei, Seyed Yaser; Esmaeili, Motahareh; Amini, Mohsen; Atyabi, Fatemeh; Ostad, Seyed Naser; Dinarvand, Rassoul

    2016-06-25

    To develop a nanoparticulate drug carrier for targeting of the inflamed intestinal mucosa, amphiphilic hyaluronic acid (HA) conjugates were synthesized, which could form self-assembled nanoparticles (NPs) in aqueous solution and budesonide (BDS) was loaded into the HANPs. Their particle sizes were in the range of 177 to 293nm with negative surface charge. The model of inflammatory CACO-2 cells was utilized to investigate the therapeutic potential of budesonide loaded HA nanocarriers. The highest expression of CD44 receptors was found on inflamed Caco-2 cells, as determined by flow cytometry. FITC-labeled HANPs revealed greater uptake in inflamed CACO-2 cells compared to untreated CACO-2 and CD44-negative cell lines, NIH3T3. BDS loaded HANPs displayed almost no toxicity indicating HANPs are excellent biocompatible nano-carriers. BDS loaded HANPs demonstrated higher anti-inflammatory effect on IL-8 and TNF-α secretion in inflamed cell model compared to the same dose of free drug. These results revealed the promising potential of HA nanoparticles as a targeted drug delivery system for IBD treatment.

  2. Modification and cross-linking parameters in hyaluronic acid hydrogels--definitions and analytical methods.

    PubMed

    Kenne, Lennart; Gohil, Suresh; Nilsson, Eva M; Karlsson, Anders; Ericsson, David; Helander Kenne, Anne; Nord, Lars I

    2013-01-02

    Definitions and methods for the quantification of degree of modification and cross-linking in cross-linked hyaluronic acid (HA) hydrogels are outlined. A novel method is presented in which the HA hydrogel is degraded by the enzyme chondroitinase AC and the digest product analyzed by size exclusion chromatography combined with electrospray ionization mass spectrometry (SEC-ESI-MS). This method allows for the determination of effective cross-linker ratio (CrR) which together with the degree of modification (MoD), determined by, e.g. (1)H NMR spectroscopy, enables the calculation of the degree of substitution (DS) and degree of cross-linking (CrD). The method, could be applicable to the major cross-linked HA hydrogels currently on the market, and is exemplified here by application to two HA hydrogels. The definitions and methods presented are important contributions in attempts to find relationships between MoD, DS and CrD to mechanical properties as well as to biocompatibility of HA hydrogels.

  3. Reducible hyaluronic acid-siRNA conjugate for target specific gene silencing.

    PubMed

    Park, Kitae; Yang, Jeong-A; Lee, Min-Young; Lee, Hwiwon; Hahn, Sei Kwang

    2013-07-17

    Despite wide applications of polymer-drug conjugates, there are only a few polymer-siRNA conjugates like poly(ethylene glycol) conjugated siRNA. In this work, reducible hyaluronic acid (HA)-siRNA conjugate was successfully developed for target specific systemic delivery of siRNA to the liver. The conjugation of siRNA to HA made it possible to form a compact nanocomplex of siRNA with relatively nontoxic linear polyethyleneimine (LPEI). After characterization of HA-siRNA conjugate by size exclusion chromatography (SEC) and gel electrophoresis, its complex formation with LPEI was investigated with a particle analyzer. The HA-siRNA/LPEI complex had a mean particle size of ca. 250 nm and a negative or neutral surface charge at physiological condition. The reducible HA-siRNA/LPEI complex showed a higher in vitro gene silencing efficiency than noncleavable HA-siRNA/LPEI complex. Furthermore, after systemic delivery, apolipoprotein B (ApoB) specific HA-siApoB/LPEI complex was target specifically delivered to the liver, which resulted in statistically significant reduction of ApoB mRNA expression in a dose dependent manner. The HA-siRNA conjugate can be effectively applied as a model system to the treatment of liver diseases using various siRNAs and relatively nontoxic polycations.

  4. Determination of modification degree in BDDE-modified hyaluronic acid hydrogel by SEC/MS.

    PubMed

    Yang, Biao; Guo, Xueping; Zang, Hengchang; Liu, Jianjian

    2015-10-20

    Determination of modification degree in BDDE-modified hyaluronic acid (HA) hydrogel is of particular interest. In this paper, three crosslinking parameters (degree of total modification, t-MOD; degree of cross-link modification, c-MOD; degree of pendent modification, p-MOD) are defined and determined by quantification of the modified fragments in hydrogel digestion by size exclusion chromatography combined with mass spectrometry (SEC-MS). The digestion products of a novel hyaluronidase HAase-B produced by Bacillus sp. A50 are studied and only a few modified fragments are identified by (1)H NMR and MS. As a result, Three HA hydrogels prepared in lab have different t-MOD, c-MOD and p-MOD, but the ratio of c-MOD to p-MOD result in the almost same value of 75%. Hydrogel products from Q-Med have nearly same t-MOD about 0.8% and c-MOD about 0.1%, the ratio of c-MOD to p-MOD is about 13%. Hydrogels from ANTEIS S.A all have much higher t-MOD values, the ratio of c-MOD and p-MOD is about 8%.

  5. Controlled drug release from cross-linked κ-carrageenan/hyaluronic acid membranes.

    PubMed

    El-Aassar, M R; El Fawal, G F; Kamoun, Elbadawy A; Fouda, Moustafa M G

    2015-01-01

    In this work, hydrogel membrane composed of; kappa carrageenan (κC) and hyaluronic acid (HA) crosslinked with epichlorohydrine is produced. The optimum condition has been established based on their water absorption properties. Tensile strength (TS) and elongation (E%) for the formed films are evaluated. The obtained films were characterized by FTIR, scanning electron microscopy (SEM) and thermal analysis. All membranes were loaded with l-carnosine as a drug model. The swelling properties and kinetics of the release of the model drug from the crosslinked hydrogel membrane were monitored in buffer medium at 37°C. The equilibrium swelling of films showed fair dependency on the high presence of HA in the hydrogel. Moreover, the cumulative release profile increased significantly and ranged from 28% to 93%, as HA increases. SEM explored that, the porosity increased by increasing HA content; consequently, drug release into the pores and channels of the membranes is facilitated. In addition, water uptake % increased as well. A slight change in TS occurred by increasing the HA% to κC, while the highest value of strain for κC membrane was 498.38% by using 3% HA. The thermal stability of the κC/HA was higher than that of HA.

  6. Hyaluronic acid-serum albumin conjugate-based nanoparticles for targeted cancer therapy.

    PubMed

    Edelman, Ravit; Assaraf, Yehuda G; Levitzky, Inna; Shahar, Tal; Livney, Yoav D

    2017-02-15

    Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44. We demonstrate that Maillard reaction-based covalent conjugates of BSA-HA self-assemble into NPs, which efficiently entrap hydrophobic cytotoxic drugs including paclitaxel and imidazoacridinones. Furthermore, BSA-HA conjugates stabilized paclitaxel and prevented its aggregation and crystallization. The diameter of the NPs was < 15 nm, thus enabling CD44 receptor-mediated endocytosis. These NPs were selectively internalized by ovarian cancer cells overexpressing CD44, but not by cognate cells lacking this HA receptor. Moreover, free HA abolished the endocytosis of drug-loaded BSA-HA conjugates. Consistently, drug-loaded NPs were markedly more cytotoxic to cancer cells overexpressing CD44 than to cells lacking CD44, due to selective internalization, which could be competitively inhibited by excess free HA. Finally, a CD44-targeted antibody which blocks receptor activity, abolished internalization of drug-loaded NPs. In conclusion, a novel cytotoxic drug-loaded nanomedicine platform has been developed, which is based on natural biocompatible biopolymers, capabale of targeting cancer cells with functional surface expression of CD44.

  7. High-titer biosynthesis of hyaluronic acid by recombinant Corynebacterium glutamicum.

    PubMed

    Cheng, Fangyu; Gong, Qianying; Yu, Huimin; Stephanopoulos, Gregory

    2016-03-01

    Hyaluronic acid (HA) plays important roles in human tissue system, thus it is highly desirable for various applications, such as in medical, clinic and cosmetic fields. The wild microbial producer of HA, streptococcus, was restricted by its potential pathogens, hence different recombinant hosts are being explored. In this work, we engineered Corynebacterium glutamicum, a GRAS (Generally Recognized as Safe) organism free of exotoxins and endotoxins to produce HA with high titer and satisfied Mw . The ssehasA gene encoding hyaluronan synthase (HasA) was artificially synthesized with codon preference of C. glutamicum. Other genes involved in the HA synthetic pathway were directly cloned from the C. glutamicum genome. The operon structures and constitutive or inducible promoters were particularly compared and the preferred environmental conditions were also optimized. Using glucose and corn syrup powder as carbon and nitrogen sources, batch cultures of the engineered C.glutamicum with operon ssehasA-hasB driven by Ptac promoter were performed in a 5 L fermentor. The maximal HA titer, productivity and yield reached 8.3 g/L, 0.24 g/L/h and 0.22 gHA/gGlucose, respectively; meanwhile the maximal Mw was 1.30 MDa. This work provides a safe and efficient novel producer of HA with huge industrial prospects.

  8. Kinetic investigation of recombinant human hyaluronidase PH20 on hyaluronic acid.

    PubMed

    Fang, Shiping; Hays Putnam, Anna-Maria A; LaBarre, Michael J

    2015-07-01

    The kinetic investigation of hyaluronidases using physiologically relevant hyaluronic acid (HA or hyaluronan) substrate will provide useful and important clues to their catalytic behavior and function in vivo. We present here a simple and sensitive method for kinetic measurement of recombinant human hyaluronidase PH20 (rHuPH20) on HA substrates with sizes ranging from 90 to 752 kDa. The method is based on 2-aminobenzamide labeling of hydrolyzed HA products combined with separation by size exclusion-ultra performance liquid chromatography coupled with fluorescence detection. rHuPH20 was found to follow Michaelis-Menten kinetics during the initial reaction time. Optimal reaction rates were observed in the pH range of 4.5-5.5. The HA substrate size did not have significant effects on the initial rate of the reaction. By studying HA substrates of 215, 357, and 752 kDa, the kinetic parameters Km, Vmax, and kcat were determined to be 0.87-0.91 mg/ml, 1.66-1.74 NM s(-1), and 40.5-42.4 s(-1), respectively. This method allows for direct measurement of kinetics using physiologically relevant HA substrates and can be applied to other hyaluronidase kinetic measurements.

  9. Hyaluronic acid alkyl derivative: A novel inhibitor of metalloproteases and hyaluronidases.

    PubMed

    Pavan, Mauro; Galesso, Devis; Secchieri, Cynthia; Guarise, Cristian

    2016-03-01

    Extracellular matrix (ECM) degradation, one of the main features of osteoarthritis, is driven by at least two major classes of enzymes: matrix metalloproteases (MMPs) and hyaluronidases. Among certain glycosaminoglycans, including natural and chemically cross-linked HAs, which are currently used as viscosupplements, the hyaluronic acid (HA) alkyl-amides (Hyadd) were here selected as the strongest MMP and hyaluronidase inhibitors. We used C. histolyticum collagenase (ChC) and bovine testicular hyaluronidase (BTH) as representative models of human MMPs and hyaluronidases, respectively. The role of the alkyl moiety was investigated using HA derivatives with varying alkyl lengths and degrees of derivatization. The selected compound was then screened against 10 different human MMPs in vitro, and the results were validated ex vivo in human synovial fluid. Hyadd-C16, identified as a lead compound, showed the highest inhibition potency against MMP13 and MMP8. The in vitro results were confirmed by the inhibition of human MMP13 (Ki=106.1 μM) and hyaluronidase-2 in the synovial fluid of patients with osteoarthritis. This study demonstrates the unique properties of Hyadd-C16, including its remarkable enzymatic inhibitory activity, which is conferred by the hydrophobic chain, and its high biocompatibility and water solubility of the HA backbone.

  10. Magnetic microparticles post-synthetically coated by hyaluronic acid as an enhanced carrier for microfluidic bioanalysis.

    PubMed

    Holubova, Lucie; Knotek, Petr; Palarcik, Jiri; Cadkova, Michaela; Belina, Petr; Vlcek, Milan; Korecka, Lucie; Bilkova, Zuzana

    2014-11-01

    Iron oxide based particles functionalized by bioactive molecules have been utilized extensively in biotechnology and biomedicine. Despite their already proven advantages, instability under changing reaction conditions, non-specific sorption of biomolecules on the particles' surfaces, and iron oxide leakage from the naked particles can greatly limit their application. As confirmed many times, surface treatment with an appropriate stabilizer helps to minimize these disadvantages. In this work, we describe enhanced post-synthetic surface modification of superparamagnetic microparticles varying in materials and size using hyaluronic acid (HA) in various chain lengths. Scanning electron microscopy, atomic force microscopy, phase analysis light scattering and laser diffraction are the methods used for characterization of HA-coated particles. The zeta potential and thickness of HA-layer of HA-coated Dynabeads M270 Amine were -50 mV and 85 nm, respectively, and of HA-coated p(GMA-MOEAA)-NH2 were -38 mV and 140 nm, respectively. The electrochemical analysis confirmed the zero leakage of magnetic material and no reactivity of particles with hydrogen peroxide. The rate of non-specific sorption of bovine serum albumin was reduced up to 50% of the naked ones. The coating efficiency and suitability of biopolymer-based microparticles for magnetically active microfluidic devices were confirmed.

  11. Bone reservoir: Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation.

    PubMed

    Martínez-Sanz, Elena; Ossipov, Dmitri A; Hilborn, Jöns; Larsson, Sune; Jonsson, Kenneth B; Varghese, Oommen P

    2011-06-10

    A strategy has been designed to develop hyaluronic acid (HA) hydrogel for in vivo bone augmentation using minimal invasive technique. A mild synthetic procedure was developed to prepare aldehyde modified HA by incorporating an amino-glycerol side chain via amidation reaction and selective oxidation of the pendent group. This modification, upon mixing with hydrazide modified HA formed hydrazone-crosslinked hydrogel within 30s that was stable at physiological pH. In vitro experiments showed no cytotoxicity of hydrogel with the controlled release of active bone morphogenic protein-2 (BMP-2). In vivo evaluation of this gel as a BMP-2 carrier was performed by injecting gels over the rat calvarium and showed bone formation in 8 weeks in correlation with the amount of BMP-2 loaded (0, 1 and 30μg) within the gel. Furthermore, hydrogels with 30μg of BMP-2 induced less bone formation upon subcutaneous injection in comparison with subperiosteal implantation. Histological examination showed newly formed bone with a high expression of osteocalcin, osteopontin and with angiogenic bone marrow when higher BMP-2 concentration was employed. Our result suggests that novel HA hydrogels could be used as a BMP-2 carrier and can promote bone augmentation for potential orthopedic applications.

  12. Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment.

    PubMed

    Silva, João P; Gonçalves, Carine; Costa, César; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G; Pedrosa, Jorge; Appelberg, Rui; Gama, F Miguel

    2016-08-10

    Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co-localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF-α). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics.

  13. The Survival of Engrafted Neural Stem Cells Within Hyaluronic Acid Hydrogels

    PubMed Central

    Liang, Yajie; Walczak, Piotr; Bulte, Jeff W.M.

    2013-01-01

    Successful cell-based therapy of neurological disorders is highly dependent on the survival of transplanted stem cells, with the overall graft survival of naked, unprotected cells in general remaining poor. We investigated the use of an injectable hyaluronic acid (HA) hydrogel for enhancement of survival of transplanted mouse C17.2 cells, human neural progenitor cells (ReNcells), and human glial-restricted precursors (GRPs). The gelation properties of the HA hydrogel were first characterized and optimized for intracerebral injection, resulting in a 25 min delayed-injection after mixing of the hydrogel components. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that the hydrogel can protect xenografted cells as evidenced by the prolonged survival of C17.2 cells implanted in immunocompetent rats (p<0.01 at day 12). The survival of human ReNcells and human GRPs implanted in the brain of immunocompetent or immunodeficient mice was also significantly improved after hydrogel scaffolding (ReNcells, p<0.05 at day 5; GRPs, p<0.05 at day 7). However, an inflammatory response could be noted two weeks after injection of hydrogel into immunocompetent mice brains. We conclude that hydrogel scaffolding increases the survival of engrafted neural stem cells, justifying further optimization of hydrogel compositions. PMID:23623429

  14. Sustained Effect of Hyaluronic Acid in Subcutaneous Administration to the Cochlear Spiral Ganglion

    PubMed Central

    Inagaki, Yozo; Fujioka, Masato; Kanzaki, Sho; Watanabe, Kotaro; Oishi, Naoki; Itakura, Go; Yasuda, Akimasa; Shibata, Shinsuke; Nakamura, Masaya; Okano, Hirotaka James; Okano, Hideyuki; Ogawa, Kaoru

    2016-01-01

    The spatiotemporal distribution of drugs in the inner ear cannot be precisely evaluated because of its small area and complex structure. In the present study, we used hyaluronic acid (HA)-dispersed luciferin to image transgenic mice and to determine the effect of HA on controlled drug delivery to the cochlea. GFAP-luc mice, which express luciferase in cochlear spiral ganglion cells, were subcutaneously administered HA-luciferin (HA-sc) or luciferin dissolved in saline (NS-sc) or intraperitoneally administered luciferin dissolved in saline (NS-ip). The bioluminescence of luciferin was monitored in vivo in real time. The peak time and half-life of fluorescence emission were significantly increased in HA-sc-treated mice compared with those in NS-sc- and NS-ip-treated mice; however, significant differences were not observed in peak photon counts. We detected differences in the pharmacokinetics of luciferin in the inner ear, including its sustained release, in the presence of HA. The results indicate the clinical potential of using HA for controlled drug delivery to the cochlea. PMID:27099926

  15. Nonmarrow Hematopoiesis Occurs in a Hyaluronic-Acid-Rich Node and Duct System in Mice

    PubMed Central

    Hwang, Sunhee; Lee, Seung J.; Park, Sang H.; Chitteti, Brahmananda R.; Srour, Edward F.; Cooper, Scott; Hangoc, Giao; Broxmeyer, Hal E.

    2014-01-01

    A hyaluronic-acid-rich node and duct system (HAR-NDS) was found on the surface of internal organs of mice, and inside their blood and lymph vessels. The nodes (HAR-Ns) were filled with immune cells of the innate system and were especially enriched with mast cells and histiocytes. They also contained hematopoietic progenitor cells (HPCs), such as granulocyte-macrophage, erythroid, multipotential progenitors, and mast cell progenitors (MCPs). MCPs were the most abundant among the HPCs in HAR-Ns. Their frequency was fivefold higher than that of the MCPs in bone marrow. In addition, the system contained pluripotent stem cells (PSCs) capable of producing CD45−Flk1+ hemangioblast-like cells, which subsequently generated various types of HPCs and differentiated blood cells. Although HAR-Ns did not appear to harbor enough number of cells capable of long-term reconstitution or short-term radioprotection of lethally irradiated recipients, bone marrow cells were able to engraft in the HAR-NDS and reconstitute hematopoietic potentials of the system. PSCs and HPCs were consistently found in intravenous, intralymphatic, and intestinal HAR-ND. We infer that PSCs and HPCs reside in the HAR-ND and that this novel system may serve as an alternative means to traffic immature and mature blood cells throughout the body. PMID:24914588

  16. Injectable hyaluronic acid-dextran hydrogels and effects of implantation in ferret vocal fold.

    PubMed

    Luo, Ying; Kobler, James B; Heaton, James T; Jia, Xinqiao; Zeitels, Steven M; Langer, Robert

    2010-05-01

    Injectable hydrogels may potentially be used for augmentation/regeneration of the lamina propria of vocal fold tissue. In this study, hyaluronic acid (HA) and dextran were chemically modified and subsequently crosslinked via formation of hydrazone bonds in phosphate buffer. Swelling ratios, degradation, and compressive moduli of the resulting hydrogels were investigated. It was found that the properties of HA-dextran hydrogels were variable and the trend of variation could be correlated with the hydrogel composition. The biocompatibility of three injectable HA-dextran hydrogels with different crosslinking density was assessed in the vocal fold region using a ferret model. It was found that HA-dextran hydrogels implanted for three weeks stimulated mild foreign-body reactions. Distinct tissue-material interactions were also observed for hydrogels made from different formulations: the hydrogel with the lowest crosslinking density was completely degraded in vivo; while material residues were visible for other types of hydrogel injections, with or without cell penetration into the implantation depending on the hydrogel composition. The in vivo results suggest that the HA-dextran hydrogel matrices can be further developed for applications of vocal fold tissue restoration.

  17. Influence of caffeine and hyaluronic acid on collagen biosynthesis in human skin fibroblasts

    PubMed Central

    Donejko, Magdalena; Przylipiak, Andrzej; Rysiak, Edyta; Głuszuk, Katarzyna; Surażyński, Arkadiusz

    2014-01-01

    Aim The aim of this study was to evaluate the effect of caffeine on collagen biosynthesis in human skin fibroblasts and the influence of hyaluronic acid (HA) on this process. Materials and methods Collagen, [3H]-thymidine incorporation, and prolidase activity were measured in confluent human skin fibroblast cultures that had been treated with 1, 2, and 5 mM caffeine and with caffeine and 500 μg/mL HA. Western immunoblot analysis was performed to evaluate expression of β1-integrin receptor, insulin-like growth factor receptor phospho-Akt protein and mitogen-activated protein kinase (phospho-extracellular signal-regulated kinase). Results Caffeine inhibited collagen biosynthesis in a dose-dependent manner. The mechanism of this process was found at the level of prolidase activity. Caffeine significantly inhibited the enzyme activity. The addition of HA had no effect on collagen biosynthesis or prolidase activity in fibroblasts incubated with caffeine. Caffeine also had an inhibitory effect on DNA biosynthesis. HA, however, did not have any significant effect on this process. The inhibition of the expression of β1-integrin and insulin-like growth factor receptor in fibroblasts incubated with the caffeine indicates a possible mechanism of inhibition of collagen biosynthesis. Conclusion Caffeine reduces collagen synthesis in human cultured skin fibroblasts. HA did not have any significant protective effect on this process. This is the first study to our knowledge that reports caffeine-induced inhibition of collagen synthesis in human skin fibroblasts. PMID:25342885

  18. Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic rabbit knee joints.

    PubMed

    Lindenhayn, K; Heilmann, H H; Niederhausen, T; Walther, H U; Pohlenz, K

    1997-05-01

    The half-life of [3H]hyaluronic acid in rabbit knee joints was estimated using two methods: (i) by following the [3H]hyaluronan content of the synovial fluid after intra-articular injection and (ii) by following the 3H2O radioactivity of plasma after intra-articular injection of [3H]hyaluronan. For normal rabbits we obtained a half-life of 15.8 hours (method I) and 17.5 +/- 1.0 hours (mean +/- SEM, method II), respectively. The second method was used to estimate the kinetics of the hyaluronan elimination from normal, sham-operated, as well as from osteoarthritic rabbit knee joints (Colombo model of osteoarthritis). Four weeks after injury, during the developing phase of osteoarthritis, the half-life of hyaluronan rose significantly to 23.5 +/- 2.1 hours and returned to normal levels (17.4 +/- 2.7 hours) 12 weeks after the operation (osteoarthritis developed). At the stage of developed osteoarthritis, the clearance rates were considerably higher than in normal rabbits.

  19. Association between Hyaluronic Acid Injections and Time-to-Total Knee Replacement Surgery.

    PubMed

    Altman, Roy; Fredericson, Michael; Bhattacharyya, Samir K; Bisson, Brad; Abbott, Thomas; Yadalam, Sashidhar; Kim, Myoung

    2016-10-01

    This study assessed the association between hyaluronic acid (HA) injections and time-to-total knee replacement (TKR) surgery for patients with knee osteoarthritis (OA). Patients 18 to 64 years of age who had TKR surgery between January 1, 2006 and December 31, 2011 were identified from the MarketScan Commercial claims database. All patients had 6 years or more of continuous enrollment prior to TKR surgery. There were two cohorts (1) patients with HA injections prior to TKR surgery and (2) patients who did not have HA injections prior to TKR surgery. Time-to-TKR was defined as the total days from the date of diagnosis of knee OA on the patient's first visit to an orthopedic surgeon to the date of TKR surgery. Results included 22,555 patients who had TKR surgery: 14,132 in the non-HA and 8,423 in the HA cohort. In this retrospective analysis of patients undergoing TKR, the median Time-to-TKR surgery was 326 days for the non-HA and 908 days for the HA cohort, a difference of 582 days. Those receiving HA injections had a median 1.6-year longer Time-to-TKR surgery versus those who did not receive HA injections. These results have both clinical and economic implications.

  20. Biodynamic performance of hyaluronic acid versus synovial fluid of the knee in osteoarthritis.

    PubMed

    Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

    2015-08-01

    Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model that can be evaluated for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, a comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA (Singh et al., 2014).

  1. Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes.

    PubMed

    Salamanna, F; Frizziero, A; Pagani, S; Giavaresi, G; Curzi, D; Falcieri, E; Marini, M; Abruzzo, P M; Martini, L; Fini, M

    2015-02-01

    The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenocytes. Twenty-four male Sprague-Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1β, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1β was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.

  2. Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery

    NASA Astrophysics Data System (ADS)

    Hayward, Stephen L.; Francis, David M.; Sis, Matthew J.; Kidambi, Srivatsan

    2015-10-01

    The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.

  3. Novel crosslinked alginate/hyaluronic acid hydrogels for nerve tissue engineering

    NASA Astrophysics Data System (ADS)

    Wang, Min-Dan; Zhai, Peng; Schreyer, David J.; Zheng, Ruo-Shi; Sun, Xiao-Dan; Cui, Fu-Zhai; Chen, Xiong-Biao

    2013-09-01

    Artificial tissue engineering scaffolds can potentially provide support and guidance for the regrowth of severed axons following nerve injury. In this study, a hybrid biomaterial composed of alginate and hyaluronic acid (HA) was synthesized and characterized in terms of its suitability for covalent modification, biocompatibility for living Schwann cells and feasibility to construct three dimensional (3D) scaffolds. Carbodiimide mediated amide formation for the purpose of covalent crosslinking of the HA was carried out in the presence of calciumions that ionically crosslink alginate. Amide formation was found to be dependent on the concentrations of carbodiimide and calcium chloride. The double-crosslinked composite hydrogels display biocompatibility that is comparable to simple HA hydrogels, allowing for Schwann cell survival and growth. No significant difference was found between composite hydrogels made from different ratios of alginate and HA. A 3D BioPlotter™ rapid prototyping system was used to fabricate 3D scaffolds. The result indicated that combining HA with alginate facilitated the fabrication process and that 3D scaffolds with porous inner structure can be fabricated from the composite hydrogels, but not from HA alone. This information provides a basis for continuing in vitro and in vivo tests of the suitability of alginate/HA hydrogel as a biomaterial to create living cell scaffolds to support nerve regeneration.

  4. Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Liopo, Anton; Su, Richard; Tsyboulski, Dmitri A.; Oraevsky, Alexander A.

    2016-08-01

    Enhanced delivery of optical clearing agents (OCA) through skin may improve sensitivity of optical and optoacoustic (OA) methods of imaging, sensing, and monitoring. This report describes a two-step method for enhancement of light penetration through skin. Here, we demonstrate that topical application of hyaluronic acid (HA) improves skin penetration of hydrophilic and lipophilic OCA and thus enhances their performance. We examined the OC effect of 100% polyethylene and polypropylene glycols (PPGs) and their mixture after pretreatment by HA, and demonstrated significant increase in efficiency of light penetration through skin. Increased light transmission resulted in a significant increase of OA image contrast in vitro. Topical pretreatment of skin for about 30 min with 0.5% HA in aqueous solution offers effective delivery of low molecular weight OCA such as a mixture of PPG-425 and polyethylene glycol (PEG)-400. The developed approach of pretreatment by HA prior to application of clearing agents (PEG and PPG) resulted in a ˜47-fold increase in transmission of red and near-infrared light and significantly enhanced contrast of OA images.

  5. Rheological characterization of hyaluronic acid derivatives as injectable materials toward nucleus pulposus regeneration.

    PubMed

    Gloria, Antonio; Borzacchiello, Assunta; Causa, Filippo; Ambrosio, Luigi

    2012-02-01

    Nucleus pulposus (NP) is the soft center of the intervertebral disc (IVD), able to resist compressive loads, while the annulus fibrosus withstands tension and gives mechanical strength. NP function may be altered as consequence of several pathologies or injury and when a damaged IVD does not properly play its role. In the past years, a great effort has been devoted to the design of injectable systems as NP substitutes. The different synthetic- and natural hydrogel-based materials proposed, present many drawbacks and, in particular, they do not seem to mimic the required behavior. In the search for natural-based systems a dodecylamide of hyaluronic acid (HA), HYADD3®, has been proved as bioactive and suitable vehicle to carry cells for NP tissue engineering, while a crosslinked HA ester, HYAFF120® showed interesting results if used as injectable acellular material. Even though these derivatives showed appropriate biological behavior up to now, data on mechanical behavior of these derivatives are still missing. In this frame, the aim of this study was to provide a rheological characterization of these HA derivatives to asses their biomechanical compatibility with the NP tissue. To this, the rheological properties of these derivatives were studied through dynamic shear tests before and after injection through needles used in the current surgical procedure. Both HA derivatives showed a 'gel-like' rheological behavior similar to the native NP tissue and this behavior was not altered by injection.

  6. Development of hyaluronic acid-based scaffolds for brain tissue engineering.

    PubMed

    Wang, Tzu-Wei; Spector, Myron

    2009-09-01

    Three-dimensional biodegradable porous scaffolds play vital roles in tissue engineering. In this study, a hyaluronic acid-collagen (HA-Coll) sponge with an open porous structure and mechanical behavior comparable to brain tissue was developed. HA-Coll scaffolds with different mixing ratios were prepared by a freeze-drying technique and crosslinked with water-soluble carbodiimide to improve mechanical stability. The pore structure of the samples was evaluated by light and scanning electron microscopy, and the mechanical behavior was analyzed by mechanical compression and tension testing. The degree of crosslinking was determined by the water absorption and trinitrobenzene sulfonic assay, and the HA content was determined by a carbazole assay. The results showed that HA-Coll scaffolds containing an open porous structure with a homogeneous pore size distribution could be fabricated. Certain features of the mechanical properties of HA-Coll scaffolds prepared with a Coll:HA mixing ratio of 1:2, and pure HA sponges, were comparable with brain tissue. Neural stem cells (NSCs) were expanded in number in monolayer culture and then seeded onto the three-dimensional scaffolds in order to investigate the effects of the different types of scaffolds on neurogenic induction of the cells. This study contributes to the understanding of the effects of HA content and crosslink treatment on pore characteristics, and mechanical behavior essential for the design of HA-Coll scaffolds suitable for NSC growth and differentiation for brain tissue engineering.

  7. Polyethylene oxide (PEO)-hyaluronic acid (HA) nanofibers with kanamycin inhibits the growth of Listeria monocytogenes.

    PubMed

    Ahire, J J; Robertson, D D; van Reenen, A J; Dicks, L M T

    2017-02-01

    Listeria monocytogenes is well known to cause prosthetic joint infections in immunocompromised patients. In this study, polyethylene oxide (PEO) nanofibers, containing kanamycin and hyaluronic acid (HA), were prepared by electrospinning at a constant electric field of 10kV. PEO nanofibers spun with 0.2% (w/v) HA and 1% (w/v) kanamycin had a smooth, bead-free structure at 30-35% relative humidity. The average diameter of the nanofibers was 83±20nm. Attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy indicated that kanamycin was successfully incorporated into PEO/HA matrix. The presence of kanamycin affects the thermal properties of PEO/HA nanofibers, as shown by differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The kanamycin-PEO-HA nanofibers (1mg; 47±3μg kanamycin) inhibited the growth of L. monocytogenes EDGe by 62%, as compared with PEO-HA nanofibers, suggesting that it may be used to coat prosthetic implants to prevent secondary infections.

  8. Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis.

    PubMed

    McCarty, M F; Russell, A L; Seed, M P

    2000-05-01

    High-molecular-weight hyaluronic acid (HA) produced by the synovium may function physiologically to aid preservation of cartilage structure and prevent arthritic pain; both the size and concentration of HA in synovial fluid are diminished in osteoarthritis (OA). Glucosamine therapy for OA can be expected to increase synovial HA production by providing rate-limiting substrate. In addition, certain sulfated glycosaminoglycans and polysaccharides - including chondroitin sulfate (CS), dermatan sulfate, and pentosan polysulfate - stimulate synovial HA production, apparently owing to a hormone-like effect triggered by the binding of these polymers to membrane proteins of synovial cells. Surprisingly, a significant proportion of orally administered CS is absorbed as intact polymers - apparently by pinocytosis. These considerations may rationalize clinical studies concluding that oral CS provides slow-onset but durable pain relief and functional improvement in OA. The possibility that oral glucosamine and CS may interact in a complementary or synergistic fashion to improve synovial fluid HA content in OA should be assessed in clinical studies, and the potential of adjunctive CS administration to improve the clinical response achievable with optimal intakes of glucosamine should likewise be evaluated. In light of the fact that the synovium virtually functions as a 'placenta' for cartilage, focusing on synovium as the target for therapeutic intervention in OA may be a rational strategy.

  9. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

    PubMed

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

  10. Matrices of a hydrophobically functionalized hyaluronic acid derivative for the locoregional tumour treatment.

    PubMed

    Palumbo, Fabio Salvatore; Puleio, Roberto; Fiorica, Calogero; Pitarresi, Giovanna; Loria, Guido Ruggero; Cassata, Giovanni; Giammona, Gaetano

    2015-10-01

    A hyaluronic acid (HA) derivative bearing octadecylamine and acylhydrazine functionalities has been here employed for the production of a paclitaxel delivering matrix for locoregional chemotherapy. Through a strategy consisting in a powder compression and a plasticization with a mixture water/ethanol, a physically assembled biomaterial, stable in solutions with physiologic ionic strengths, has been produced. Two different drug loading strategies have been adopted, by using paclitaxel as chemotherapic agent, and obtained samples have been assayed in terms of release in enhanced solubility conditions and in vitro and in vivo tumoural cytotoxicity. In particular sample with the best releasing characteristics was chosen for an in vivo evaluation against a HCT-116 xenograft on mice. Local tumour establishment and metastatic diffusion was assayed locally at the site of xenograft implantation and at the tributary lymph nodes. Obtained results demonstrated how loading procedure influenced paclitaxel crystallinity into the matrix and consequently drug diffusion and its cytoreductive potential. Chosen paclitaxel loaded matrix was able to drastically inhibit HCT-116 establishment and metastatic diffusion.

  11. Esthetic Reconstruction of Diastema with Adhesive Tooth-Colored Restorations and Hyaluronic Acid Fillers

    PubMed Central

    2017-01-01

    Objective. This report presents a comprehensive esthetic treatment with adhesive tooth-colored restorations in a combination with hyaluronic acid (HA) fillers of diastema in an orthodontic patient with relapse. Case Report. A 36-year-old female patient consulted about 1.5–2 mm midline diastema after an orthodontic relapse of replacing missing central incisors with lateral incisors and dark-colored gingival tissue as a result of a metal post and core with porcelain fused to a metal (PFM) crown at the left lateral incisor. Restorative treatments included replacing the PFM with all-ceramic material and placing a ceramic veneer on the right lateral incisor. To close the space, crown forms of both lateral incisors were altered. A direct resin composite was then used to reform right and left canines to a more ideal lateral incisor shape. An HA fillers injection was used to fill the remaining open gingival embrasure. Eighteen months after treatment, the interdental papilla remained stable and the patient was satisfied with the result. Conclusion. Esthetic reconstruction of diastema and open gingival embrasure in this case can be accomplished without orthodontic retreatment. Tooth-colored restorations and HA filler injection appear as a promising modality to address this patient's esthetic concern. PMID:28386488

  12. Sustained Small Molecule Delivery from Injectable Hyaluronic Acid Hydrogels through Host-Guest Mediated Retention

    PubMed Central

    Mealy, Joshua E.; Rodell, Christopher B.; Burdick, Jason A.

    2015-01-01

    Self-assembled and injectable hydrogels have many beneficial properties for the local delivery of therapeutics; however, challenges still exist in the sustained release of small molecules from these highly hydrated networks. Host-guest chemistry between cyclodextrin and adamantane has been used to create supramolecular hydrogels from modified polymers. Beyond assembly, this chemistry may also provide increased drug retention and sustained release through the formation of inclusion complexes between drugs and cyclodextrin. Here, we engineered a two-component system from adamantane-modified and β-cyclodextrin (CD)-modified hyaluronic acid (HA), a natural component of the extracellular matrix, to produce hydrogels that are both injectable and able to sustain the release of small molecules. The conjugation of cyclodextrin to HA dramatically altered its affinity for hydrophobic small molecules, such as tryptophan. This interaction led to lower molecule diffusivity and the release of small molecules for up to 21 days with release profiles dependent on CD concentration and drug-CD affinity. There was significant attenuation of release from the supramolecular hydrogels (~20% release in 24h) when compared to hydrogels without CD (~90% release in 24h). The loading of small molecules also had no effect on hydrogel mechanics or self-assembly properties. Finally, to illustrate this controlled delivery approach with clinically used small molecule pharmaceuticals, we sustained the release of two widely used drugs (i.e., doxycycline and doxorubicin) from these hydrogels. PMID:26693019

  13. Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues

    PubMed Central

    Kim, Iris L.; Khetan, Sudhir; Baker, Brendon M.; Chen, Christopher S.; Burdick, Jason A.

    2013-01-01

    Electrospinning has recently gained much interest due to its ability to form scaffolds that mimic the nanofibrous nature of the extracellular matrix, such as the size and depth-dependent alignment of collagen fibers within hyaline cartilage. While much progress has been made in developing bulk, isotropic hydrogels for tissue engineering and understanding how the microenvironment of such scaffolds affects cell response, these effects have not been extensively studied in a nanofibrous system. Here, we show that the mechanics (through intrafiber crosslink density) and adhesivity (through RGD density) of electrospun hyaluronic acid (HA) fibers significantly affect human mesenchymal stem cell (hMSC) interactions and gene expression. Specifically, hMSC spreading, proliferation, and focal adhesion formation were dependent on RGD density, but not on the range of fiber mechanics investigated. Moreover, traction-mediated fiber displacements generally increased with more adhesive fibers. The expression of chondrogenic markers, unlike trends in cell spreading and cytoskeletal organization, was influenced by both fiber mechanics and adhesivity, in which softer fibers and lower RGD densities generally enhanced chondrogenesis. This work not only reveals concurrent effects of mechanics and adhesivity in a fibrous context, but also highlights fibrous HA hydrogels as a promising scaffold for future cartilage repair strategies. PMID:23623322

  14. Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns.

    PubMed

    Friedrich, Emily E; Sun, Liang Tso; Natesan, Shanmugasundaram; Zamora, David O; Christy, Robert J; Washburn, Newell R

    2014-05-01

    Biomaterials capable of neutralizing specific cytokines could form the basis for treating a broad range of conditions characterized by intense, local inflammation. Severe burns, spanning partial- to full-thickness of the dermis, can result in complications due to acute inflammation that contributes to burn progression, and early mediation may be a key factor in rescuing thermally injured tissue from secondary necrosis to improve healing outcomes. In this work, we examined the effects on burn progression and influence on the inflammatory microenvironment of topical application of anti-tumor necrosis factor-α (anti-TNF-α) alone, mixed with hyaluronic acid (HA) or conjugated to HA. We found that non-conjugated anti-TNF-α decreased macrophage infiltration to a greater extent than that conjugated to HA; however, there was little effect on the degree of progression or IL-1β levels. A simple transport model is proposed to analyze the results, which predicts qualitative and quantitative differences between untreated burn sites and those treated with the conjugates. Our results indicate that conjugation of anti-TNF-α to high molecular weight HA provides sustained, local modulation of the post-injury inflammatory responses compared to direct administration of non-conjugated antibodies.

  15. Bisphosphonate-functionalized hyaluronic acid showing selective affinity for osteoclasts as a potential treatment for osteoporosis.

    PubMed

    Kootala, Sujit; Ossipov, Dmitri; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander; Hilborn, Jöns

    2015-08-01

    Current treatments for osteoporosis involve the administration of high doses of bisphosphonates (BPs) over a number of years. However, the efficiency of the absorption of these drugs and specificity towards targeted osteoclastic cells is still suboptimal. In this study, we have exploited the natural affinity of high (H) and low (L) molecular-weight hyaluronic acid (HA) towards a cluster of differentiation 44 (CD44) receptors on osteoclasts to use it as a biodegradable targeting vehicle. We covalently bonded BP to functionalised HA (HA-BP) and found that HA-BP conjugates were highly specific to osteoclastic cells and reduced mature osteoclast numbers significantly more than free BP. To study the uptake of HA-BP, we fluorescently derivatised the polymer-drug with fluorescein B isothiocyanate (FITC) and found that L-HA-BP could seamlessly enter osteoclastic cells. Alternatively, we tested polyvinyl alcohol (PVA) as a synthetic polymer delivery vehicle using similar chemistry to link BP and found that osteoclast numbers did not reduce in the same way. These findings could pave the way for biodegradable polymers to be used as vehicles for targeted delivery of anti-osteoporotic drugs.

  16. Synergistic interaction between TS-polysaccharide and hyaluronic acid: implications in the formulation of eye drops.

    PubMed

    Uccello-Barretta, Gloria; Nazzi, Samuele; Zambito, Ylenia; Di Colo, Giacomo; Balzano, Federica; Sansò, Marco

    2010-08-16

    An interaction between tamarind seed polysaccharide (TSP) and hyaluronic acid (HA) in aqueous solution has been ascertained. Various TSP/HA mixtures have been studied as the basis for the development of a potential excipient for eye drops synergistically improved over those of the separate polymers. Information about the nature of interpolymer interactions, and their dependence on TSP/HA ratios were obtained by NMR spectroscopy in solution. Superior mucin affinity of TSP/HA mixtures with respect to the single polysaccharides was assessed by NMR proton selective relaxation rate measurements. The mucoadhesivity of the TSP/HA (3/2) mixture, evaluated in vitro by NMR or viscometry, and in vivo by its mean and maximum residence time in rabbit precorneal area, is stronger than that of the component polysaccharides or the TSP/HA mixtures of different composition. TSP/HA (3/2) is little viscous and well tolerated by rabbit eyes. It stabilizes the tear film, thereby prolonging the residence of ketotifen fumarate and diclofenac sodium in tear fluid, but is unable to permeabilize the cornea. In conclusion, mucoadhesivity is responsible for the TSP/HA (3/2) synergistic enhancement of either extra- or intra-ocular drug bioavailability.

  17. Structural Analysis and Mechanical Characterization of Hyaluronic Acid-Based Doubly Cross-Linked Networks

    PubMed Central

    Jha, Amit K.; Hule, Rohan A.; Jiao, Tong; Teller, Sean S.; Clifton, Rodney J.; Duncan, Randall L.; Pochan, Darrin J.; Jia, Xinqiao

    2009-01-01

    We have created a new class of hyaluronic acid (HA)-based hydrogel materials with HA hydrogel particles (HGPs) embedded in and covalently cross-linked to a secondary network. HA HGPs with an average diameter of ∼900 nm and narrow particle size distribution were synthesized using a refined reverse micelle polymerization technique. The average mesh size of the HGPs was estimated to be approximately 5.5 to 7.0 nm by a protein uptake experiment. Sodium periodate oxidation not only introduced aldehyde groups to the particles but also reduced the average particle size. The aldehyde groups generated were used as reactive handles for subsequent cross-linking with an HA derivative containing hydrazide groups. The resulting macroscopic gels contain two distinct hierarchical networks (doubly cross-linked networks, DXNs): one within individual particles and another among different particles. Bulk gels (BGs) formed by direct mixing of HA derivatives with mutually reactive groups were included for comparison. The hydrogel microstructures were collectively characterized by microscopy and neutron scattering techniques. Their viscoelasticity was quantified at low frequencies (0.1−10 Hz) using a controlled stress rheometer and at high frequencies (up to 200 Hz) with a home-built torsional wave apparatus. Both BGs and DXNs are stable elastic gels that become stiffer at higher frequencies. The HA-based DXN offers unique structural hierarchy and mechanical properties that are suitable for soft tissue regeneration. PMID:20046226

  18. Hyaluronic acid prevents immunosuppressive drug-induced ovarian damage via up-regulating PGRMC1 expression

    PubMed Central

    Zhao, Guangfeng; Yan, Guijun; Cheng, Jie; Zhou, Xue; Fang, Ting; Sun, Haixiang; Hou, Yayi; Hu, Yali

    2015-01-01

    Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. PMID:25558795

  19. Hyaluronic acid-supported combination of water insoluble immunostimulatory compounds for anti-cancer immunotherapy.

    PubMed

    Shin, Woo Jung; Noh, Hyun Jong; Noh, Young-Woock; Kim, Sohyun; Um, Soong Ho; Lim, Yong Taik

    2017-01-02

    A novel powder-form combination adjuvant system containing two immunostimulatory compounds was firstly developed and evaluated as a therapeutic intervention for cancer immunotherapy. With the help of hyaluronic acid (HA), water insoluble monophosphoryl lipid A (MPL), QS21 and imiquimod (R837), could be easily dispersed in aqueous solution and lyophilized as powder-form, which have an advantage in room-temperature storage stability compared with those conventional liquid formulation that requires cold storage. Two kinds of HA-based combination vaccine adjuvants (HA/MPL/QS21, HMQ and HA/MPL/R837, HMR) contributed to the increase of both humoral and cellular immunity, which is very important for efficient cancer immunotherapy. Through the challenge experiments in EG7-OVA (mouse lymphoma-expressing OVA) tumor-bearing mice model, we found out that the immunostimulatory effects of HMQ and HMR were successful in the inhibition of tumor proliferation. Taken together, both HA-based powder-form combination adjuvant systems are expected to be used as potent prophylactic and therapeutic cancer vaccine.

  20. Effects of high molecular weight hyaluronic acid on induced arthritis of the temporomandibular joint in rats.

    PubMed

    Lemos, George Azevedo; Rissi, Renato; Pimentel, Edson Rosa; Palomari, Evanisi Teresa

    2015-07-01

    High molecular weight hyaluronic acid (HMWHA) has been used to treat temporomandibular joint (TMJ) disorders, but controversial results have been described. This study aimed to characterize the morphological and biochemical actions of HMWHA on induced arthritis of the TMJ. Twenty-four male Wistar rats were used, and arthritis of the TMJ was induced through an intra-articular injection of Complete Freund's Adjuvant (CFA) (50 μl). One week after arthritis induction, the animals were treated with HMWHA (once per week for three weeks). Histological analyses were performed using sections stained with hematoxylin-eosin, toluidine blue and Picrosirius. Were also performed histomorphometric analysis and birefringence of collagenous fibers (polarization microscopy). Biochemical analyses of TMJ tissues were carried out through measurements of sulfated glycosaminoglycans and zymography for evaluation of metalloproteinase-2 and -9 (MMP-2 and -9). Data were analyzed using paired t-test and unpaired t-test, with a 5% significance level. HMWHA reduced histologic changes and thickness of the articular disc, led to a greater arrangement of collagenous fibers, lower concentration of sulfated glycosaminoglycans and lower activity in all isoforms of MMP-2 and -9 in TMJs with induced arthritis. These findings suggest that HMWHA may exert a protective effect on the TMJ.

  1. Mechanical and biocompatible characterization of a cross-linked collagen-hyaluronic acid wound dressing.

    PubMed

    Kirk, James F; Ritter, Gregg; Finger, Isaac; Sankar, Dhyana; Reddy, Joseph D; Talton, James D; Nataraj, Chandra; Narisawa, Sonoko; Millán, José Luis; Cobb, Ronald R

    2013-01-01

    Collagen scaffolds have been widely employed as a dermal equivalent to induce fibroblast infiltrations and dermal regeneration in the treatment of chronic wounds and diabetic foot ulcers. Cross-linking methods have been developed to address the disadvantages of the rapid degradation associated with collagen-based scaffolds. To eliminate the potential drawbacks associated with glutaraldehyde cross-linking, methods using a water soluble carbodiimide have been developed. In the present study, the glycosaminoglycan (GAG) hyaluronic acid (HA), was covalently attached to an equine tendon derived collagen scaffold using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) to create ntSPONGE The HA was shown to be homogeneously distributed throughout the collagen matrix. In vitro analyses of the scaffold indicated that the cross-linking enhanced the biological stability by decreasing the enzymatic degradation and increasing the thermal denaturation temperature. The material was shown to support the attachment and proliferation of mouse L929 fibroblast cells. In addition, the cross-linking decreased the resorption rate of the collagen as measured in an intramuscular implant model in rabbits. The material was also shown to be biocompatible in a variety of in vitro and in vivo assays. These results indicate that this cross-linked collagen-HA scaffold, ntSPONGE has the potential for use in chronic wound healing.

  2. Subureteral Injection with Small-Size Dextranomer/Hyaluronic Acid Copolymer: Is It Really Efficient?

    PubMed Central

    Tan, Özgür; Farahvash, Amirali; Senol, Cem; Gümüstas, Hüseyin; Atay, Irfan; Deniz, Nuri

    2016-01-01

    The aim of this study was to evaluate the clinical results of patients with vesicoureteral reflux, which were treated with subureteral injection of small-size (80–120 μm) dextranomer/hyaluronic acid copolymer (Dx/HA). Data of 75 children (105 renal units) who underwent STING procedure with small-size Dx/HA for the treatment of vesicoureteral reflux (VUR) in our clinic between 2008 and 2012 were retrospectively analyzed. Preoperative reflux grade and side, injection indication, postoperative urinary infections and urinary symptoms, voiding cystourethrogram, and renal scintigraphy results were evaluated. The success rate of the procedure was 100% in patients with grades 1 and 2 reflux, 91% in patients with grade 3 reflux, and 82.6% in patients with grade 4. Overall success rate of the treated patients was 97%. Endoscopic subureteric injection with Dx/HA procedure has become a reasonable minimally invasive alternative technique to open surgery, long-term antibiotic prophylaxis, and surveillance modalities in treatment of VUR in terms of easy application, low costs and complication rates, and high success rates. Injection material composed of small-size dextranomer microspheres seems superior to normal size Dx/HA, together with offering similar success with low cost. PMID:28105412

  3. Thiolated Carboxymethyl-Hyaluronic-Acid-Based Biomaterials Enhance Wound Healing in Rats, Dogs, and Horses

    PubMed Central

    Yang, Guanghui; Prestwich, Glenn D.; Mann, Brenda K.

    2011-01-01

    The progression of wound healing is a complicated but well-known process involving many factors, yet there are few products on the market that enhance and accelerate wound healing. This is particularly problematic in veterinary medicine where multiple species must be treated and large animals heal slower, oftentimes with complicating factors such as the development of exuberant granulation tissue. In this study a crosslinked-hyaluronic-acid (HA-) based biomaterial was used to treat wounds on multiple species: rats, dogs, and horses. The base molecule, thiolated carboxymethyl HA, was first found to increase keratinocyte proliferation in vitro. Crosslinked gels and films were then both found to enhance the rate of wound healing in rats and resulted in thicker epidermis than untreated controls. Crosslinked films were used to treat wounds on forelimbs of dogs and horses. Although wounds healed slower compared to rats, the films again enhanced wound healing compared to untreated controls, both in terms of wound closure and quality of tissue. This study indicates that these crosslinked HA-based biomaterials enhance wound healing across multiple species and therefore may prove particularly useful in veterinary medicine. Reduced wound closure times and better quality of healed tissue would decrease risk of infection and pain associated with open wounds. PMID:23738117

  4. Temporal MRI characterization of gelatin/hyaluronic acid/chondroitin sulfate sponge for cartilage tissue engineering.

    PubMed

    Chou, Cheng-Hung; Lee, Herng-Sheng; Siow, Tiing Yee; Lin, Ming-Huang; Kumar, Amit; Chang, Yue-Cune; Chang, Chen; Huang, Guo-Shu

    2013-08-01

    A tri-copolymer sponge consisting of gelatin, hyaluronic acid, and chondroitin sulfate (GHC) was designed to mimic the cartilage environment in vivo for cartilage regeneration. The present study aimed to temporally characterize the magnetic resonance relaxation time of GHC constructs in vivo in a rodent heterotopic model. GHC sponges with cells (GHCc) or without cells (GHC) implanted in rat leg muscle were monitored using MRI (4.7 T MR scanner) on day 0, 7, 14, and 21 after implantation. The results revealed that the transverse relaxation time (T2) of GHC constructs decreased significantly over time when compared to the T2 of GHCc constructs. However, the longitudinal relaxation time (T1) of GHCc and GHC constructs remained stable. Moreover, hematoxylin and eosin and immunohistochemical staining with antibodies to S100 protein, and types I and II collagen showed that normal morphology, phenotype, and function of chondrocytes were preserved in the GHCc construct. Thus, we concluded that GHC constructs adequately support chondrocyte growth and function. On top of that, T2 may be a useful tool for monitoring cartilage regeneration in GHC constructs.

  5. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    NASA Astrophysics Data System (ADS)

    Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

    2012-12-01

    In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

  6. The procoagulant properties of hyaluronic acid-collagen (I)/chitosan complex film.

    PubMed

    Hu, Yi; Wu, Yangzhe; Cai, Jiye; Ma, Shuyuan; Wang, Xiaoping

    2009-01-01

    Biomaterial-induced human platelet activation remains one of the most crucial factors to determine the procoagulant properties of the biomaterial. In this experiment, a new type of biomacromolecule complex film (hyaluronic acid-collagen (I)/chitosan, HCC) was prepared using the electrostatic self-assembly method. Then the procoagulant properties of this complex film were characterized. Based on the nano-resolution of atomic force microscopy, the platelet-derived microparticles (PMPs) that present the activation of platelets were clearly visualized on the membrane surface of platelets for the first time, and the measurement indicated that the size of PMPs is around 50-110 nm. Furthermore, the results of AFM measurement were confirmed by flow cytometry analysis. The expression of CD62P (P-selectin) dramatically increased after the platelet-rich plasma interacted with the biomaterial solution. From the results, we could draw the conclusion that this biomacromolecule complex film has promising procoagulant properties, and has the potential to be practically used as procoagulant material.

  7. Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds.

    PubMed

    Anisha, B S; Biswas, Raja; Chennazhi, K P; Jayakumar, R

    2013-11-01

    The aim of this work was to develop an antimicrobial sponge composed of chitosan, hyaluronic acid (HA) and nano silver (nAg) as a wound dressing for diabetic foot ulcers (DFU) infected with drug resistant bacteria. nAg (5-20 nm) was prepared and characterized. The nanocomposite sponges were prepared by homogenous mixing of chitosan, HA and nAg followed by freeze drying to obtain a flexible and porous structure. The prepared sponges were characterized using SEM and FT-IR. The porosity, swelling, biodegradation and haemostatic potential of the sponges were also studied. Antibacterial activity of the prepared sponges was analysed using Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Klebsiella pneumonia. Chitosan-HA/nAg composite sponges showed potent antimicrobial property against the tested organisms. Sponges containing higher nAg (0.005%, 0.01% and 0.02%) concentrations showed antibacterial activity against MRSA. Cytotoxicity and cell attachment studies were done using human dermal fibroblast cells. The nanocomposite sponges showed a nAg concentration dependent toxicity towards fibroblast cells. Our results suggest that this nanocomposite sponges could be used as a potential material for wound dressing for DFU infected with antibiotic resistant bacteria if the optimal concentration of nAg exhibiting antibacterial action with least toxicity towards mammalian cells is identified.

  8. Hyaluronic Acid-Based Hydrogels: from a Natural Polysaccharide to Complex Networks

    PubMed Central

    Xu, Xian; Jha, Amit K.; Harrington, Daniel A.; Farach-Carson, Mary C.; Jia, Xinqiao

    2012-01-01

    Hyaluronic acid (HA) is one of nature's most versatile and fascinating macromolecules. Being an essential component of the natural extracellular matrix (ECM), HA plays an important role in a variety of biological processes. Inherently biocompatible, biodegradable and non-immunogenic, HA is an attractive starting material for the construction of hydrogels with desired morphology, stiffness and bioactivity. While the interconnected network extends to the macroscopic level in HA bulk gels, HA hydrogel particles (HGPs, microgels or nanogels) confine the network to microscopic dimensions. Taking advantage of various scaffold fabrication techniques, HA hydrogels with complex architecture, unique anisotropy, tunable viscoelasticity and desired biologic outcomes have been synthesized and characterized. Physical entrapment and covalent integration of hydrogel particles in a secondary HA network give rise to hybrid networks that are hierarchically structured and mechanically robust, capable of mediating cellular activities through the spatial and temporal presentation of biological cues. This review highlights recent efforts in converting a naturally occurring polysaccharide to drug releasing hydrogel particles, and finally, complex and instructive macroscopic networks. HA-based hydrogels are promising materials for tissue repair and regeneration. PMID:22419946

  9. On the thickness uniformity of micropatterns of hyaluronic acid in a soft lithographic molding method

    NASA Astrophysics Data System (ADS)

    Jeong, Hoon Eui; Suh, Kahp Y.

    2005-06-01

    A soft lithographic molding is a simple and yet robust method for fabricating well-defined microstructures of a hydrophilic biopolymer such as polyethylene glycol and polysaccharide over a large area. The method consists of three steps: placing a polydimethylsiloxane mold with a bas-relief pattern onto a drop-dispensed polymer solution typically dissolved in water, letting the mold and the solution undisturbed in contact until solvent evaporates completely, and leaving behind a polymer replica after mold removal. In such a molding process, water can only evaporate from the edges of the mold due to impermeable nature of polydimethylsiloxane to water, resulting in a nonuniform distribution of film thickness or pattern height. Here we examine systematically how the evaporation rate affects the thickness distribution of the resulting microstructures by evaporating the solution of hyaluronic acid in various conditions. To compare with a theory, we also present a simple theoretical model based on one-dimensional conservation equation for a liquid film, which is in good agreement with the experimental data.

  10. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    PubMed Central

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor. PMID:26213465

  11. Effect of Intra-articular Hyaluronic Acid Injection on Hemiplegic Shoulder Pain After Stroke

    PubMed Central

    2016-01-01

    Objective To evaluate the efficacy of intra-articular hyaluronic acid (IAHA) injection for hemiplegic shoulder pain (HSP) after stroke. Methods Thirty-one patients with HSP and limited range of motion (ROM) without spasticity of upper extremity were recruited. All subjects were randomly allocated to group A (n=15) for three weekly IAHA injection or group B (n=16) for a single intra-articular steroid (IAS) injection. All injections were administered by an expert physician until the 8th week using a posterior ultrasonography-guided approach. Shoulder joint pain was measured using the Wong-Baker Scale (WBS), while passive ROM was measured in the supine position by an expert physician. Results There were no significant intergroup differences in WBS or ROM at the 8th week. Improvements in forward flexion and external rotation were observed from the 4th week in the IAHA group and the 8th week in the IAS group. Subjects experienced a statistically significant improvement in pain from the 1st week in the IAS and from the 8th week in IAHA group, respectively. Conclusion IAHA seems to have a less potent ability to reduce movement pain compared to steroid in the early period. However, there was no statistically significant intergroup difference in WBS and ROM improvements at the 8th week. IAHA might be a good alternative to steroid for managing HSP when the use of steroid is limited. PMID:27847713

  12. Scientific evidence on the usefulness of intraarticular hyaluronic acid injection in the management of temporomandibular dysfunction.

    PubMed

    Escoda-Francolí, Jaume; Vázquez-Delgado, Eduardo; Gay-Escoda, Cosme

    2010-07-01

    Hyaluronic acid (HA) is found in high concentrations in cartilage and synovial fluid, and is an important component of the extracellular matrixes-exerting joint lubrication and buffering actions thanks to its viscoelastic properties. The present study examines the scientific evidence found in the current literature on the usefulness of the intraarticular injection of HA in patients with temporomandibular dysfunction. A literature search was made up until May 2008 in the following databases: PubMed / MEDLINE. Of the articles found in the literature, the present review included 18 relevant studies on the application of HA in the temporomandibular joint (TMJ). The quality, level of evidence and strength of recommendation of the articles was evaluated based on the "Strength of Recommendation Taxonomy" criteria. It is concluded that type A level of recommendation exists in favor of the intraarticular injection of HA in dysfunction of the TMJ. However, further studies are needed to establish the true therapeutic effects and to identify the best dosing regimen.

  13. Pervaporation dehydration of ethanol by hyaluronic acid/sodium alginate two-active-layer composite membranes.

    PubMed

    Gao, Chengyun; Zhang, Minhua; Ding, Jianwu; Pan, Fusheng; Jiang, Zhongyi; Li, Yifan; Zhao, Jing

    2014-01-01

    The composite membranes with two-active-layer (a capping layer and an inner layer) were prepared by sequential spin-coatings of hyaluronic acid (HA) and sodium alginate (NaAlg) on the polyacrylonitrile (PAN) support layer. The SEM showed a mutilayer structure and a distinct interface between the HA layer and the NaAlg layer. The coating sequence of two-active-layer had an obvious influence on the pervaporation dehydration performance of membranes. When the operation temperature was 80 °C and water concentration in feed was 10 wt.%, the permeate fluxes of HA/Alg/PAN membrane and Alg/HA/PAN membrane were similar, whereas the separation factor were 1130 and 527, respectively. It was found that the capping layer with higher hydrophilicity and water retention capacity, and the inner layer with higher permselectivity could increase the separation performance of the composite membranes. Meanwhile, effects of operation temperature and water concentration in feed on pervaporation performance as well as membrane properties were studied.

  14. Proteomic Profiling of Neuroblastoma Cells Adhesion on Hyaluronic Acid-Based Surface for Neural Tissue Engineering.

    PubMed

    Yang, Ming-Hui; Chen, Ko-Chin; Chiang, Pei-Wen; Chung, Tze-Wen; Chen, Wan-Jou; Chu, Pei-Yu; Chen, Sharon Chia-Ju; Lu, Yi-Shan; Yuan, Cheng-Hui; Wang, Ming-Chen; Lin, Chia-Yang; Huang, Ying-Fong; Jong, Shiang-Bin; Lin, Po-Chiao; Tyan, Yu-Chang

    2016-01-01

    The microenvironment of neuron cells plays a crucial role in regulating neural development and regeneration. Hyaluronic acid (HA) biomaterial has been applied in a wide range of medical and biological fields and plays important roles in neural regeneration. PC12 cells have been reported to be capable of endogenous NGF synthesis and secretion. The purpose of this research was to assess the effect of HA biomaterial combining with PC12 cells conditioned media (PC12 CM) in neural regeneration. Using SH-SY5Y cells as an experimental model, we found that supporting with PC12 CM enhanced HA function in SH-SY5Y cell proliferation and adhesion. Through RP-nano-UPLC-ESI-MS/MS analyses, we identified increased expression of HSP60 and RanBP2 in SH-SY5Y cells grown on HA-modified surface with cotreatment of PC12 CM. Moreover, we also identified factors that were secreted from PC12 cells and may promote SH-SY5Y cell proliferation and adhesion. Here, we proposed a biomaterial surface enriched with neurotrophic factors for nerve regeneration application.

  15. Structural and rheological characterization of hyaluronic acid-based scaffolds for adipose tissue engineering.

    PubMed

    Borzacchiello, Assunta; Mayol, Laura; Ramires, Piera A; Pastorello, Andrea; Di Bartolo, Chiara; Ambrosio, Luigi; Milella, Evelina

    2007-10-01

    In this study the attention has been focused on the ester derivative of hyaluronic acid (HA), HYAFF11, as a potential three-dimensional scaffold in adipose tissue engineering. Different HYAFF11 sponges having different pore sizes, coated or not coated with HA, have been studied from a rheological and morphological point of view in order to correlate their structure to the macroscopic and degradation properties both in vitro and in vivo, using rat model. The in vitro results indicate that the HYAFF11 sponges possess proper structural and mechanical properties to be used as scaffolds for adipose tissue engineering and, among all the analysed samples, uncoated HYAFF11 large-pore sponges showed a longer lasting mechanical stability. From the in vivo results, it was observed that the elastic modulus of scaffolds seeded with preadipocytes, the biohybrid constructs, and explanted after 3 months of implantation in autologous rat model are over one order of magnitude higher than the corresponding values for the native tissue. These results could suggest that the implanted scaffolds can be invaded and populated by different cells, not only adipocytes, that can produce new matrix having different properties from that of adipose tissue.

  16. Biocompatible hyaluronic acid polymer-coated quantum dots for CD44+ cancer cell-targeted imaging

    NASA Astrophysics Data System (ADS)

    Wang, Hening; Sun, Hongfang; Wei, Hui; Xi, Peng; Nie, Shuming; Ren, Qiushi

    2014-10-01

    The cysteamine-modified hyaluronic acid (HA) polymer was employed to coat quantum dots (QDs) through a convenient one-step reverse micelle method, with the final QDs hydrodynamic size of around 22.6 nm. The HA coating renders the QDs with very good stability in PBS for more than 140 days and resistant to large pH range of 2-12. Besides, the HA-coated QDs also show excellent fluorescence stability in BSA-containing cell culture medium. In addition, the cell culture assay indicates no significant cytotoxicity for MD-MB-231 breast cancer cells, and its targeting ability to cancer receptor CD44 has been demonstrated on two breast cancer cell lines. The targeting mechanism was further proved by the HA competition experiment. This work has established a new approach to help solve the stability and toxicity problems of QDs, and moreover render the QDs cancer targeting property. The current results indicate that the HA polymer-coated QDs hold the potential application for both in vitro and in vivo cancer imaging researches.

  17. Therapeutic effect of epidural hyaluronic acid in a rat model of foraminal stenosis

    PubMed Central

    Nahm, Francis Sahngun; Lee, Pyung Bok; Choe, Ghee Young; Lim, Young Jin; Kim, Yong Chul

    2017-01-01

    Purpose Since receiving a warning from the US Food and Drug Administration (FDA) about injection of corticosteroids into the epidural space having serious adverse events, we have sought alternative medications for injection at this site. Hyaluronic acid (HA) has anti-adhesive, anti-inflammatory, and lubricating properties, so could potentially be useful for spinal pain. The exact mechanism by which spinal stenosis develops is not fully understood, but is likely to involve inflammation. Therefore, we hypothesized that HA could have a therapeutic effect in spinal stenosis. This study evaluated the effects of epidural administration of HA on alleviation of pain in a rat model of foraminal stenosis. Materials and methods After creating the animal model, HA (HA group) or saline solution (S group) was administered via an epidural catheter. The paw-withdrawal threshold to mechanical stimulation and motor dysfunction were monitored for up to 21 days. Tissue was collected to evaluate the degree of adhesion, inflammation in the perineural area, and chromatolysis in the dorsal root ganglion (DRG). Results The mechanical withdrawal threshold was restored in the HA group but not in the S group (P < 0.001). The HA group also showed less fibrosis (P = 0.026) and less chromatolysis (P = 0.002) than the S group. Conclusion HA administered epidurally had a therapeutic effect on the allodynia and hyperalgesia induced by chronic compression of the DRG. PMID:28182130

  18. Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy.

    PubMed

    Xiao, Bo; Han, Moon Kwon; Viennois, Emilie; Wang, Lixin; Zhang, Mingzhen; Si, Xiaoying; Merlin, Didier

    2015-11-14

    Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.

  19. Effects of molecular weight of grafted hyaluronic acid on wear initiation.

    PubMed

    Lee, Dong Woog; Banquy, Xavier; Das, Saurabh; Cadirov, Nicholas; Jay, Gregory; Israelachvili, Jacob

    2014-05-01

    Hyaluronic acid (HA) of different molecular weights (Mw) was grafted onto mica surfaces to study the effects of Mw on the conformation and wear protection properties of a grafted HA (gHA) layer in lubricin (LUB) and bovine synovial fluid (BSF) using a surface forces apparatus. The Mw of gHA had significant effects on the wear pressure (Pw), at which point the wear initiates. Increasing the gHA Mw from 51 to 2590kDa increased Pw from 4 to 8MPa in LUB and from 15 to 31MPa in BSF. The 2590kDa gHA in BSF had the best wear protection (Pw∼31MPa), even though it exhibited the highest friction coefficient (μ∼0.35), indicating that a low μ does not necessarily result in good wear protection, as is often assumed. The normal force profile indicated that BSF confines the gHA structure, making it polymer brush-like, commonly considered as an excellent structure for boundary lubrication.

  20. Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides.

    PubMed

    Han, Su-Eun; Kang, Hyungu; Shim, Ga Yong; Kim, Sun Jae; Choi, Han-Gon; Kim, Jiseok; Hahn, Sei Kwang; Oh, Yu-Kyoung

    2009-02-01

    In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide G3139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.

  1. Shell-crosslinked hyaluronic acid nanogels for live monitoring of hyaluronidase activity in vivo.

    PubMed

    Kim, Jihyun; Chong, Youhoon; Mok, Hyejung

    2014-06-01

    A hyaluronidase (HAdase) has been noticed as a potential drug target as well as prognostic marker because of its close associations with tumor invasion, metastasis, and angiogenesis. Accordingly, precise monitoring of HAdase activity in vivo seems to be crucial not only for the evaluation of HAdase activity but also for non-invasive molecular imaging. In our study, we propose a new organic, near-infrared fluorescence imaging probe, indocyanine green (ICG)-based stimuli-responsive fluorescence probe for selective imaging of HAdases with appreciable signal-to-noise (S/N) ratios in serum and in vivo. Shell-crosslinked hyaluronic acid (HA) nanogels (sc-nanogels) are generated via a reducible covalent linkage which incorporate ICG derivatives. The ICG-embeded HA nanogels via shell-crosslinking have preferable properties for ideal selective imaging and detection of HAdase activity in vivo. The sc-nanogels exhibit prominent chemical stability against external light, greatly control background signals in serum, and small size compared to use of self-assembled ICG-based carriers. Collapsed ICG in the hydrogel core is selectively disentangled by HAdase treatment for selective near-infrared imaging without unwanted background signal. The newly designed sc-nanogels may have great potential to serve as probes for improved selective imaging of HAdase-associated diseases in clinics as well as HAdase-activity screening in vivo.

  2. A novel gene therapy vector based on hyaluronic acid and solid lipid nanoparticles for ocular diseases.

    PubMed

    Apaolaza, Paola Stephanie; Delgado, Diego; del Pozo-Rodríguez, Ana; Gascón, Alicia Rodríguez; Solinís, M Ángeles

    2014-04-25

    The introduction of therapeutic genes in target tissues is considered as a novel tool for the treatment of several diseases. We have developed nanoparticles consisting on SLNs, protamine (P) and hyaluronic acid (HA) as carrier for gene therapy. Stable complexes positively charged and with a particle size ranging from 240 nm to 340 nm were obtained. Transfection studies in ARPE-19 and HEK-293 cells showed the versatility of vectors to efficiently transfect cells with different division rate, widening the potential applications of SLN-based vectors. In ARPE 19cells, the incorporation of P and HA induced almost a 7-fold increase in the transfection capacity of SLNs. The CD44 inhibition studies suggested the participation of this receptor in the internalization of the vectors in this cell line. The intracellular disposition of DNA showed that the HA is able to modulate the high degree of condensation of DNA due to the protamine inside the cells; an important fact, if the vector is uptaken via non-degradative endocytosis. Besides, the therapeutic plasmid which encodes the protein retinoschisin was employed achieving a positive transfection in ARPE-19 cells, showing a promising application of this new non-viral system for the treatment of X-linked juvenile retinoschisis by gene therapy.

  3. Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats.

    PubMed

    Nakamura, Hidehiro; Gotoh, Masafumi; Kanazawa, Tomonoshin; Ohta, Keisuke; Nakamura, Keiichirou; Honda, Hirokazu; Ohzono, Hiroki; Shimokobe, Hisao; Mitsui, Yasuhiro; Shirachi, Isao; Okawa, Takahiro; Higuchi, Fujio; Shirahama, Masahiro; Shiba, Naoto; Matsueda, Satoko

    2015-10-01

    Corticosteroids (CS) or hyaluronic acid (HA) is used in subacromial injection for the conservative treatment of rotator cuff tears (RCT); this study addresses the question of how CS and HA affect the tendon tissue and fibroblasts in vitro and in rats. Cell proliferation assays were performed in human tendon fibroblasts from RCT. Rats underwent surgery to create RCT, and the surgical sites were injected with CS or HA. The rotator cuff tendons were subjected to biomechanical testing, microscopic and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and ultrastructural analysis. Cell proliferation was significantly decreased with CS in vitro (p < 0.05). Maximal load of CS-treated tendons was significantly decreased compared with that of HA-treated tendons (p < 0.05), as well as PCNA(+) cells at 2 weeks (p < 0.05). Ultrastructural observations of the CS-treated rats detected apoptosis of tendon fibroblasts 24 h after surgery. Histological and biomechanical data 4 weeks after surgery were not significant among the three groups. Unlike HA, CS caused cell death, and inhibition of the proliferation of tendon fibroblasts, leading to a delay of tendon healing involved and a subsequent decrease of biomechanical strength at the surgical site.

  4. Self-assembled nanoparticles based on amphiphilic chitosan derivative and hyaluronic acid for gene delivery.

    PubMed

    Liu, Ya; Kong, Ming; Cheng, Xiao Jie; Wang, Qian Qian; Jiang, Li Ming; Chen, Xi Guang

    2013-04-15

    The present work described nanoparticles (NPs) made of oleoyl-carboxymethy-chitosan (OCMCS)/hyaluronic acid (HA) using coacervation process as novel potential carriers for gene delivery. An N/P ratio of 5 and OCMCS/HA weight ratio of 4 were the optimal conditions leading to the smallest (164.94 nm), positive charged (+14.2 mV) and monodispersed NPs. OCMCS-HA/DNA (OHD) NPs showed higher in vitro DNA release rates and increased cellular uptake by Caco-2 cells due to the HA involved in NPs. The MTT survival assay indicated no significant cytotoxicity. The transfection efficiency of OHD NPs was 5-fold higher than OCMCS/DNA (OD) NPs; however, it decreased significantly in the presence of excess free HA. The results indicated that OHD NPs internalized in Caco-2 cells were mediated by the hyaluronan receptor CD44. The data obtained in the present research gave evidence of the potential of OHD NPs for the targeting and further transfer of genes to the epithelial cells.

  5. Carboxymethyl chitosan-mediated synthesis of hyaluronic acid-targeted graphene oxide for cancer drug delivery.

    PubMed

    Yang, Huihui; Bremner, David H; Tao, Lei; Li, Heyu; Hu, Juan; Zhu, Limin

    2016-01-01

    In order to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release, a new drug carrier was developed. Graphene oxide (GO) was first modified with carboxymethyl chitosan (CMC), followed by conjugation of hyaluronic acid (HA) and fluorescein isothiocyanate (FI). The resulting GO-CMC-FI-HA conjugate was characterized and used as a carrier to encapsulate the anticancer drug doxorubicin (DOX) to study in vitro release behavior. The drug loading capacity is as high as 95% and the drug release rate under tumor cell microenvironment of pH 5.8 is significantly higher than that under physiological conditions of pH 7.4. Cell uptake studies show that the GO-CMC-FI-HA/DOX complex can specifically target cancer cells, which are over-expressing CD44 receptors and effectively inhibit their growth. The above results suggest that the functionalized graphene-based material has potential applications for targeted delivery and controlled release of anticancer drugs.

  6. Hyaluronic acid uptake in the assessment of sinusoidal endothelial cell damage after cold storage and normothermic reperfusion of rat livers.

    PubMed

    Reinders, M E; van Wagensveld, B A; van Gulik, T M; Frederiks, W M; Chamuleau, R A; Endert, E; Klopper, P J

    1996-01-01

    The uptake of hyaluronic acid (HA) was used to assess preservation damage to sinusoidal endothelial cells (SEC) during cold storage and subsequent normothermic reperfusion of rat livers. After 8, 16, 24, and 48 h storage in University of Wisconsin (UW) solution, livers were gravity-flushed via the portal vein with a standard volume of cold UW solution containing 50 micrograms/l HA. The effluent was collected for analysis of HA, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). The mean uptake of HA at 0 h was 59.1% +/- 4.6% (mean +/- SEM). After 8 h of storage, HA uptake was similar (55.5% +/- 7.3%), whereas after 16 h of storage it was reduced to 34.7% +/- 5.8%. At 24 and 48 h of storage, no uptake of HA was found. In a second series of experiments, livers were stored in UW solution and subsequently reperfused for 90 min with a Krebs-Henseleit solution (37 degrees C) in a recirculating system containing 150 micrograms/l HA. Following 8 h of storage, 34.6% +/- 8.0% of the initial HA concentration was taken up from the perfusate. After 16 and 24 h of storage, no uptake of HA was found. The results of this study indicate that damage to SEC occurs progressively during storage, leading to zero uptake of HA by the rat livers at 24 h of cold ischemia time. Additional reperfusion injury to the SEC was demonstrated by the reduced ability of the SEC to take up HA following normothermic reperfusion. The uptake of exogenous HA in preserved livers, used as a tool to assess SEC injury, enables the detection of early preservation damage.

  7. Efficacy of dextranomer hyaluronic acid and polyacrylamide hydrogel in endoscopic treatment of vesicoureteral reflux: A comparative study

    PubMed Central

    Blais, Anne-Sophie; Morin, Fannie; Cloutier, Jonathan; Moore, Katherine; Bolduc, Stéphane

    2015-01-01

    Introduction: Various bulking agents are available for vesicoureteral reflux (VUR) endoscopic treatment, but their inconsistent success rates and costs are concerns for urologists. Recently, polyacrylamide hydrogel (PAHG) has been shown to have a good overall success rate, which seems comparable to dextranomer hyaluronic acid (Dx/HA), currently the most popular bulking agent. Our objective was to compare the short-term success rate of PAHG and Dx/HA for VUR endoscopic treatment in children. Methods: We performed a prospective non-randomized study using PAHG and Dx/HA to treat VUR grades I to IV in pediatric patients. All patients underwent endoscopic sub-ureteric injection of PAHG or Dx/HA, using the double-HIT technique, followed by a 3-month postoperative renal ultrasound and voiding cystourethrogram. Treatment success was defined as the absence of de novo or worsening hydronephrosis and absence of VUR. Results: A total of 90 pediatric patients underwent an endoscopic injection: 45 patients (78 ureters) with PAHG and 45 patients (71 ureters) with Dx/HA. The mean injected volume of PAHG and Dx/HA was 1.1 mL and 1.0 mL, respectively. The overall success rate 3 months after a single treatment was 73.1% for PAHG and 77.5% for Dx/HA. Postoperatively, 1 patient in each group presented with acute pyelonephritis and 2 patients in the Dx/HA group developed symptomatic ureteral obstruction. Conclusion: Success rates of PAGH and Dx/HA in endoscopic injections for VUR treatment were comparable. The rate of resolution obtained with Dx/HA was equivalent to those previously published. The lower cost of PAHG makes it an interesting option. PMID:26225173

  8. New Adipose Tissue Formation by Human Adipose-Derived Stem Cells with Hyaluronic Acid Gel in Immunodeficient Mice

    PubMed Central

    Huang, Shu-Hung; Lin, Yun-Nan; Lee, Su-Shin; Chai, Chee-Yin; Chang, Hsueh-Wei; Lin, Tsai-Ming; Lai, Chung-Sheng; Lin, Sin-Daw

    2015-01-01

    Background: Currently available injectable fillers have demonstrated limited durability. This report proposes the in vitro culture of human adipose-derived stem cells (hASCs) on hyaluronic acid (HA) gel for in vivo growth of de novo adipose tissue. Methods: For in vitro studies, hASCs were isolated from human adipose tissue and were confirmed by multi-lineage differentiation and flow cytometry. hASCs were cultured on HA gel. The effectiveness of cell attachment and proliferation on HA gel was surveyed by inverted light microscopy. For in vivo studies, HA gel containing hASCs, hASCs without HA gel, HA gel alone were allocated and subcutaneously injected into the subcutaneous pocket in the back of nude mice (n=6) in each group. At eight weeks post-injection, the implants were harvested for histological examination by hematoxylin and eosin (H&E) stain, Oil-Red O stain and immunohistochemical staining. The human-specific Alu gene was examined. Results: hASCs were well attachment and proliferation on the HA gel. In vivo grafts showed well-organized new adipose tissue on the HA gel by histologic examination and Oil-Red O stain. Analysis of neo-adipose tissues by PCR revealed the presence of the Alu gene. This study demonstrated not only the successful culture of hASCs on HA gel, but also their full proliferation and differentiation into adipose tissue. Conclusions: The efficacy of injected filler could be permanent since the reduction of the volume of the HA gel after bioabsorption could be replaced by new adipose tissue generated by hASCs. This is a promising approach for developing long lasting soft tissue filler. PMID:25589892

  9. Hyaluronic acid production and hyaluronidase activity in the newt iris during lens regeneration

    SciTech Connect

    Kulyk, W.M.; Zalik, S.E.; Dimitrov, E.

    1987-09-01

    The process of lens regeneration in newts involves the dedifferentiation of pigmented iris epithelial cells and their subsequent conversion into lens fibers. In vivo this cell-type conversion is restricted to the dorsal region of the iris. We have examined the patterns of hyaluronate accumulation and endogenous hyaluronidase activity in the newt iris during the course of lens regeneration in vivo. Accumulation of newly synthesized hyaluronate was estimated from the uptake of (/sup 3/H)glucosamine into cetylpyridinium chloride-precipitable material that was sensitive to Streptomyces hyaluronidase. Endogenous hyaluronidase activity was determined from the quantity of reducing N-acetylhexosamine released upon incubation of iris tissue extract with exogenous hyaluronate substrate. We found that incorporation of label into hyaluronate was consistently higher in the regeneration-activated irises of lentectomized eyes than in control irises from sham-operated eyes. Hyaluronate labeling was higher in the dorsal (lens-forming) region of the iris than in ventral (non-lens-forming) iris tissue during the regeneration process. Label accumulation into hyaluronate was maximum between 10 and 15 days after lentectomy, the period of most pronounced dedifferentiation in the dorsal iris epithelium. Both normal and regenerating irises demonstrated a high level of endogenous hyaluronidase activity with a pH optimum of 3.5-4.0. Hyaluronidase activity was 1.7 to 2 times higher in dorsal iris tissue than in ventral irises both prior to lentectomy and throughout the regeneration process. We suggest that enhanced hyaluronate accumulation may facilitate the dedifferentiation of iris epithelial cells in the dorsal iris and prevent precocious withdrawal from the cell cycle. The high level of hyaluronidase activity in the dorsal iris may promote the turnover and remodeling of extracellular matrix components required for cell-type conversion.

  10. Human Disease Isolates of Serotype M4 and M22 Group A Streptococcus Lack Genes Required for Hyaluronic Acid Capsule Biosynthesis

    PubMed Central

    Flores, Anthony R.; Jewell, Brittany E.; Fittipaldi, Nahuel; Beres, Stephen B.; Musser, James M.

    2012-01-01

    ABSTRACT Group A streptococcus (GAS) causes human pharyngitis and invasive infections and frequently colonizes individuals asymptomatically. Many lines of evidence generated over decades have shown that the hyaluronic acid capsule is a major virulence factor contributing to these infections. While conducting a whole-genome analysis of the in vivo molecular genetic changes that occur in GAS during longitudinal human pharyngeal interaction, we discovered that serotypes M4 and M22 GAS strains lack the hasABC genes necessary for hyaluronic acid capsule biosynthesis. Using targeted PCR, we found that all 491 temporally and geographically diverse disease isolates of these two serotypes studied lack the hasABC genes. Consistent with the lack of capsule synthesis genes, none of the strains produced detectable hyaluronic acid. Despite the lack of a hyaluronic acid capsule, all strains tested multiplied extensively ex vivo in human blood. Thus, counter to the prevailing concept in GAS pathogenesis research, strains of these two serotypes do not require hyaluronic acid to colonize the upper respiratory tract or cause abundant mucosal or invasive human infections. We speculate that serotype M4 and M22 GAS have alternative, compensatory mechanisms that promote virulence. PMID:23131832

  11. A chitosan-hyaluronic acid hydrogel scaffold for periodontal tissue engineering.

    PubMed

    Miranda, Diego G; Malmonge, Sônia M; Campos, Doris M; Attik, Nina G; Grosgogeat, Brigitte; Gritsch, Kerstin

    2016-11-01

    The current challenge in treating periodontitis is regenerating the periodontium. This motivates tissue-engineering researchers to develop scaffolds as artificial matrices that give mechanical support for osteoblasts, cementoblasts, gingival and periodontal ligament fibroblast cells. In this study, modified hyaluronic acid (HA) and chitosan (CS) were employed to create a hybrid CS-HA hydrogel scaffold for periodontal regeneration. CS, HA, and CS-HA scaffolds were obtained by freeze-drying technique, resulting in porous structures suitable for use in tissue engineering. Scaffolds were submitted to gamma and UV-sterilization without significant morphology changes. The ATR-FTIR spectra of CS-HA hydrogels showed peaks at 377 cm(-1) , 1566 cm(-1) , and 1614 cm(-1) , representing secondary amide, primary amine, and carboxyl acid respectively, and it was also observed the emergence of peaks at 886 cm(-1) , which probably represents the Schiff base formed in the case of hybrid CS-HA hydrogels. The scaffolds presented a high rate of PBS uptake, reaching values higher than 95%. Thermal degradation of HA scaffolds was around 225°C and CS was around 285°C. The ATR-FTIR spectra and swelling degree were slightly disturbed mainly after gamma sterilization, but degradation temperature did not change after sterilization. The performance of the CS-HA hydrogel scaffolds for in vitro cell culture was tested using NIH3T3 and MG63 cell lines. The Alamar Blue test showed a significant increase in cellular viability and high CD44 expression, suggesting that the cells migrated more when seeded onto the scaffolds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1691-1702, 2016.

  12. The Competing Effects of Hyaluronic and Methacrylic Acid in Model Contact Lenses.

    PubMed

    Weeks, Andrea; Subbaraman, Lakshman N; Jones, Lyndon; Sheardown, Heather

    2012-01-01

    The aim of this study was to determine the influence of hyaluronic acid (HA) on lysozyme sorption in model contact lenses containing varying amounts of methacrylic acid (MAA). One model conventional hydrogel (poly(2-hydroxyethyl methacrylate) (pHEMA)) and two model silicone hydrogels (pHEMA, methacryloxypropyltris(trimethylsiloxy)silane (pHEMA TRIS) and N,N-dimethylacrylamide, TRIS (DMAA TRIS)) lens materials were prepared with and without MAA at two different concentrations (1.7 and 5%). HA, along with dendrimers, was loaded into these model contact lens materials and then cross-linked with 1-ethyl-3-(3-dimethylamino propyl)-carbodiimide (EDC). Equilibrium water content (EWC), advancing water contact angle and lysozyme sorption on these lens materials were investigated. In the HA-containing materials, the presence (P < 0.05) and amount (P < 0.05) of MAA increased the EWC of the materials. For most materials, addition of MAA reduced the advancing contact angles (P < 0.05) and for all the materials, the addition of HA further improved hydrophilicity (P < 0.05). For the non-HA containing hydrogels, the presence (P < 0.05) and amount (P < 0.05) of MAA increased lysozyme sorption. The presence of HA decreased lysozyme sorption for all materials (P < 0.05). MAA appears to work synergistically with HA to increase the EWC in addition to improving the hydrophilicity of model pHEMA-based and silicone hydrogel contact lens materials. Hydrogel materials that contain HA have tremendous potential as hydrophilic, protein-resistant contact lens materials.

  13. Dual Enzyme-Responsive Capsules of Hyaluronic Acid-block-Poly(Lactic Acid) for Sensing Bacterial Enzymes.

    PubMed

    Tücking, Katrin-Stephanie; Grützner, Verena; Unger, Ronald E; Schönherr, Holger

    2015-07-01

    The synthesis of novel amphiphilic hyaluronic acid (HYA) and poly(lactic acid) (PLA) block copolymers is reported as the key element of a strategy to detect the presence of pathogenic bacterial enzymes. In addition to the formation of defined HYA-block-PLA assemblies, the encapsulation of fluorescent reporter dyes and the selective enzymatic degradation of the capsules by hyaluronidase and proteinase K are studied. The synthesis of the dual enzyme-responsive HYA-b-PLA is carried out by copper-catalyzed Huisgen 1,3-dipolar cycloaddition. The resulting copolymers are assembled in water to form vesicular structures, which are characterized by scanning electron microscopy, transmission electron microscopy, dynamic light scattering (DLS), and fluorescence lifetime imaging microscopy (FLIM). DLS measurements show that both enzymes cause a rapid decrease in the hydrodynamic diameter of the nanocapsules. Fluorescence spectroscopy data confirm the liberation of encapsulated dye, which indicates the disintegration of the capsules and validates the concept of enzymatically triggered payload release. Finally, cytotoxicity assays confirm that the HYA-b-PLA nanocapsules are biocompatible with primary human dermal microvascular endothelial cells.

  14. Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy

    NASA Astrophysics Data System (ADS)

    Xiao, Bo; Han, Moon Kwon; Viennois, Emilie; Wang, Lixin; Zhang, Mingzhen; Si, Xiaoying; Merlin, Didier

    2015-10-01

    Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments

  15. Hyaluronic-Acid-Hydroxyapatite Colloidal Gels Combined with Micronized Native ECM as Potential Bone Defect Fillers.

    PubMed

    Dennis, S Connor; Whitlow, Jonathan; Detamore, Michael S; Kieweg, Sarah L; Berkland, Cory J

    2017-01-10

    One of the grand challenges in translational regenerative medicine is the surgical placement of biomaterials. For bone regeneration in particular, malleable and injectable colloidal gelsare frequently designed to exhibit self-assembling and shear-response behavior which facilitates biomaterial placement in tissue defects. The current study demonstrated that by combining native extracellular matrix (ECM) microparticles, i.e., demineralized bone matrix (DBM) and decellularized cartilage (DCC), with hyaluronic acid (HA) and hydroxyapatite (HAP) nanoparticles, a viscoelastic colloidal gel consisting exclusively of natural materials was achieved. Rheological testing of HA-ECM suspensions and HA-HAP-ECM colloidal gels concluded either equivalent or substantially higher storage moduli (G' ≈ 100-10 000 Pa), yield stresses (τy ≈ 100-1000 Pa), and viscoelastic recoveries (G'recovery ≥ 87%) in comparison with controls formulated without ECM, which indicated a previously unexplored synergy in fluid properties between ECM microparticles and HA-HAP colloidal networks. Notable rheological differences were observed between respective DBM and DCC formulations, specifically in HA-HAP-DBM mixtures, which displayed a mean 3-fold increase in G' and a mean 4-fold increase in τy from corresponding DCC mixtures. An initial in vitro assessment of these potential tissue fillers as substrates for cell growth revealed that all formulations of HA-ECM and HA-HAP-ECM showed no signs of cytotoxicity and appeared to promote cell viability. Both DBM and DCC colloidal gels represent promising platforms for future studies in bone and cartilage tissue engineering. Overall, the current study identified colloidal gels constructed exclusively of natural materials, with viscoelastic properties that may facilitate surgical placement for a wide variety of therapeutic applications.

  16. Phytosome-hyaluronic acid systems for ocular delivery of L-carnosine

    PubMed Central

    Abdelkader, Hamdy; Longman, Michael R; Alany, Raid G; Pierscionek, Barbara

    2016-01-01

    This study reports on L-carnosine phytosomes as an alternative for the prodrug N-acetyl-L-carnosine as a novel delivery system to the lens. L-carnosine was loaded into lipid-based phytosomes and hyaluronic acid (HA)-dispersed phytosomes. L-carnosine-phospholipid complexes (PC) of different molar ratios, 1:1 and 1:2, were prepared by the solvent evaporation method. These complexes were characterized with thermal and spectral analyses. PC were dispersed in either phosphate buffered saline pH 7.4 or HA (0.1% w/v) in phosphate buffered saline to form phytosomes PC1:1, PC1:2, and PC1:2 HA, respectively. These phytosomal formulations were studied for size, zeta potential, morphology, contact angle, spreading coefficient, viscosity, ex vivo transcorneal permeation, and cytotoxicity using primary human corneal cells. L-carnosine-phospholipid formed a complex at a 1:2 molar ratio and phytosomes were in the size range of 380–450 nm, polydispersity index of 0.12–0.2. The viscosity of PC1:2 HA increased by 2.4 to 5-fold compared with HA solution and PC 1:2, respectively; significantly lower surface tension, contact angle, and greater spreading ability for phytosomes were also recorded. Ex vivo transcorneal permeation parameters showed significantly controlled corneal permeation of L-carnosine with the novel carrier systems without any significant impact on primary human corneal cell viability. Ex vivo porcine lenses incubated in high sugar media without and with L-carnosine showed concentration-dependent marked inhibition of lens brunescence indicative of the potential for delaying changes that underlie cataractogenesis that may be linked to diabetic processes. PMID:27366062

  17. Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

    SciTech Connect

    Svensson Holm, Ann-Charlotte B.; Bengtsson, Torbjoern; Grenegard, Magnus; Lindstroem, Eva G.

    2012-03-10

    Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodelling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in platelet-induced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling.

  18. A novel fibrin gel derived from hyaluronic acid-grafted fibrinogen.

    PubMed

    Yang, Chiung L; Chen, Hui W; Wang, Tzu C; Wang, Yng J

    2011-04-01

    Fibrinogen is a major plasma protein that forms a three-dimensional fibrin gel upon being activated by thrombin. In this study, we report the synthesis and potential applications of hybrid molecules composed of fibrinogen coupled to the reducing ends of short-chain hyaluronic acids (sHAs) by reductive amination. The grafting of sHAs to fibrinogen was verified by analyzing particle size, zeta potential and gel-electrophoretic mobility of the hybrid molecules. The sHA-fibrinogen hybrid molecules with graft ratios (sHA/fibrinogen) of up to 6.5 retained the ability to form gels in response to thrombin activation. The sHA-fibrin gels were transparent in appearance and exhibited high water content, which were characteristics distinct from those of gels formed by mixtures of sHAs and fibrinogen. The potential applications of the sHA-fibrin gels were evaluated. The sHA-fibrinogen gel with a graft ratio of 3.6 (S3.6F) was examined for its ability to encapsulate and support the differentiation of ATDC5 chondrocyte-like cells. Compared with the fibrinogen-formed gel, cells cultured in the S3.6F gel exhibited increased lacunae formation; moreover, the abundance of cartilaginous extracellular matrix molecules and the expression of chondrocyte marker genes, such as aggrecan, collagen II and Sox9, were also significantly increased. Our data suggest that the three-dimensional gel formed by the sHA-fibrinogen hybrid is a better support than the fibrin gel for chondrogenesis induction.

  19. Multivalent hyaluronic acid bioconjugates improve sFlt-1 activity in vitro.

    PubMed

    Altiok, Eda I; Santiago-Ortiz, Jorge L; Svedlund, Felicia L; Zbinden, Aline; Jha, Amit K; Bhatnagar, Deepika; Loskill, Peter; Jackson, Wesley M; Schaffer, David V; Healy, Kevin E

    2016-07-01

    Anti-VEGF drugs that are used in conjunction with laser ablation to treat patients with diabetic retinopathy suffer from short half-lives in the vitreous of the eye resulting in the need for frequent intravitreal injections. To improve the intravitreal half-life of anti-VEGF drugs, such as the VEGF decoy receptor sFlt-1, we developed multivalent bioconjugates of sFlt-1 grafted to linear hyaluronic acid (HyA) chains termed mvsFlt. Using size exclusion chromatography with multiangle light scattering (SEC-MALS), SDS-PAGE, and dynamic light scattering (DLS), we characterized the mvsFlt with a focus on the molecular weight contribution of protein and HyA components to the overall bioconjugate size. We found that mvsFlt activity was independent of HyA conjugation using a sandwich ELISA and in vitro angiogenesis assays including cell survival, migration and tube formation. Using an in vitro model of the vitreous with crosslinked HyA gels, we demonstrated that larger mvsFlt bioconjugates showed slowed release and mobility in these hydrogels compared to low molecular weight mvsFlt and unconjugated sFlt-1. Finally, we used an enzyme specific to sFlt-1 to show that conjugation to HyA shields sFlt-1 from protein degradation. Taken together, our findings suggest that mvsFlt bioconjugates retain VEGF binding affinity, shield sFlt-1 from enzymatic degradation, and their movement in hydrogel networks (in vitro model of the vitreous) is controlled by both bioconjugate size and hydrogel network mesh size. These results suggest that a strategy of multivalent conjugation could substantially improve drug residence time in the eye and potentially improve therapeutics for the treatment of diabetic retinopathy.

  20. Metabolic engineering of Pichia pastoris for production of hyaluronic acid with high molecular weight.

    PubMed

    Jeong, Euijoon; Shim, Woo Yong; Kim, Jung Hoe

    2014-09-20

    The high molecular weight (>1 MDa) of hyaluronic acid (HA) is important for its biological functions. The reported limiting factors for the production of HA with high molecular weight (MW) by microbial fermentation are the insufficient HA precursor pool and cell growth inhibition. To overcome these issues, the Xenopus laevis xhasA2 and xhasB genes encoding hyaluronan synthase 2 (xhasA2) and UDP-glucose dehydrogenase (xhasB), were expressed in Pichia pastoris widely used for production of heterologous proteins. In this study, expression vectors containing various combination cassettes of HA pathway genes including xhasA2 and xhasB from X. laevis as well as UDP-glucose pyrophosphorylase (hasC), UDP-N-acetylglucosamine pyrophosphorylase (hasD) and phosphoglucose isomerase (hasE) from P. pastoris were constructed and tested. First, HA pathway genes were overexpressed using pAO815 and pGAPZB vectors, resulting in the production of 1.2 MDa HA polymers. Second, in order to decrease hyaluronan synthase expression a strong AOX1 promoter in the xhasA2 gene was replaced by a weak AOX2 promoter which increased the mean MW of HA to 2.1 MDa. Finally, the MW of HA polymer was further increased to 2.5 MDa by low-temperature cultivation (26 °C) which reduced cell growth inhibition. The yield of HA production by the P. pastoris recombinant strains in 1L of fermentation culture was 0.8-1.7 g/L.

  1. Impaired wound healing in diabetes: the rationale for clinical use of hyaluronic acid plus silver sulfadiazine.

    PubMed

    Prosdocimi, M; Bevilacqua, C

    2012-12-01

    Diabetes-related chronic cutaneous lesions are a serious and common problem, as well as a major cause for hospital admissions, although no general consensus has been reached on the best available treatment for this frequent pathological condition. The primary objective of this review is to analyze the most recent evidence supporting the clinical use of a formulation containing hyaluronic acid (HA) and silver sulfadiazine (SSD) in the diabetic patient. This formulation has been widely used in cutaneous lesions of various etiology, both acute and chronic. The mechanisms underlying tissue repair are altered in the diabetic patient with respect to a healthy individual, namely for a diminished response of the keratinocytes and a reduced capacity of the endothelial cells to form new vessels (neoangiogenesis). Since HA favours the tissue repair process through various mechanisms, among these an increased angiogenic response and an activation of the keratinocytes, its application in diabetic lesions is a rational choice. SSD has been widely used in acute cutaneous lesions, particularly in burns, where it is considered the "gold standard" by which other treatments are measured. The efficacy of SSD in terms of antibacterial activity spectrum on various types of microorganisms, with a favourable safety profile, supports the potential use of SSD in diabetic lesions, where the presence of infection caused by bacteria resistant to most available antibiotics, but not to SSD, is rather frequent. In conclusion, the combined use of HA and SSD in the diabetic patient proves a rational choice and is potentially capable of improving the general clinical situation, on the basis of the synergic effect to control infection and accelerate the tissue repair process.

  2. ANTITUMOR ACTIVITY OF HYALURONIC ACID SYNTHESIS INHIBITOR 4-METHYLUMBELLIFERONE IN PROSTATE CANCER CELLS

    PubMed Central

    Lokeshwar, Vinata B.; Lopez, Luis E.; Munoz, Daniel; Chi, Andrew; Shirodkar, Samir P.; Lokeshwar, Soum D.; Escudero, Diogo O.; Dhir, Neetika; Altman, Norman

    2010-01-01

    4-methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on prostate cancer cells. 4-MU inhibited proliferation, motility and invasion of DU145, PC3-ML, LNCaP, C4-2B and/or LAPC-4 cells. At IC50 for HA synthesis (0.4 mM), 4-MU induced > 3-fold apoptosis in prostate cancer cells, which could be prevented by HA addition. 4-MU induced caspase-8, -9 and -3 activation, PARP cleavage, up-regulation of Fas-L, Fas, FADD and DR4 and down regulation of bcl-2, phospho-bad, bcl-XL, phospho-Akt, phospho-IKB, phospho-ErbB2 and phospho-EGFR. At IC50, 4-MU also caused > 90% inhibition of NFkB reporter activity which was prevented partially by HA addition. With the exception of caveolin-1, HA prevented the 4-MU induced down regulation of HA receptors (CD44, RHAMM), matrix-degrading enzymes (MMP-2, MMP-9), IL-8, and chemokine receptors (CXCR1, CXCR4, CXCR7) at protein and mRNA levels. Expression of myristoylated-Akt rescued 4-MU induced apoptosis and inhibition of cell growth and IL-8, RHAMM, HAS2, CD44 and MMP-9 expression. Oral administration of 4-MU significantly decreased PC3-ML tumor growth (> 3-fold), when treatment was started either on the day of tumor cell injection or after the tumors became palpable, without organ toxicity, changes in serum chemistry or body weight. Tumors from 4-MU treated animals showed reduced microvessel density (~ 3-fold) and HA expression but increased TUNEL positive cells and expression of apoptosis-related molecules. Therefore, anticancer effects of 4-MU, an orally bioavailable and relatively non-toxic agent, are primarily mediated by inhibition of HA signaling. PMID:20332231

  3. Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

    PubMed

    Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

    2015-09-01

    This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile.

  4. High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury

    NASA Astrophysics Data System (ADS)

    Khaing, Zin Z.; Milman, Brian D.; Vanscoy, Jennifer E.; Seidlits, Stephanie K.; Grill, Raymond J.; Schmidt, Christine E.

    2011-08-01

    A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.

  5. Determination of substitution positions in hyaluronic acid hydrogels using NMR and MS based methods.

    PubMed

    Wende, Frida J; Gohil, Suresh; Mojarradi, Hotan; Gerfaud, Thibaud; Nord, Lars I; Karlsson, Anders; Boiteau, Jean-Guy; Kenne, Anne Helander; Sandström, Corine

    2016-01-20

    In hydrogels of cross-linked polysaccharides, the total amount of cross-linker and the degree of cross-linking influence the properties of the hydrogel. The substitution position of the cross-linker on the polysaccharide is another parameter that can influence hydrogel properties; hence methods for detailed structural analysis of the substitution pattern are required. NMR and LC-MS methods were developed to determine the positions and amounts of substitution of 1,4-butanediol diglycidyl ether (BDDE) on hyaluronic acid (HA), and for the first time it is shown that BDDE can react with any of the four available hydroxyl groups of the HA disaccharide repeating unit. This was achieved by studying di-, tetra-, and hexasaccharides obtained from degradation of BDDE cross-linked HA hydrogel by chondroitinase. Furthermore, amount of linker substitution at each position was shown to be dependent on the size of the oligosaccharides. For the disaccharide, substitutions were predominantly at ΔGlcA-OH2 and GlcNAc-OH6 while in the tetra- and hexasaccharides, it was mainly at the reducing end GlcNAc-OH4. In the disaccharide there was no substitution at this position. Since chondroitinase is able to completely hydrolyse non-substituted HA into unsaturated disaccharides, these results indicate that the enzyme is prevented to cleave on the non-reducing side of an oligosaccharide substituted at the reducing end GlcNAc-OH4. The procedure can be adopted for the determination of substitution positions in other types of polymers.

  6. Near Infrared Fluorescent Nanoparticles Derived from Hyaluronic Acid Improve Tumor Contrast for Image-Guided Surgery

    PubMed Central

    Hill, Tanner K.; Kelkar, Sneha S.; Wojtynek, Nicholas E.; Souchek, Joshua J.; Payne, William M.; Stumpf, Kristina; Marini, Frank C.; Mohs, Aaron M.

    2016-01-01

    Tumor tissue that remains undetected at the primary surgical site can cause tumor recurrence, repeat surgery, and treatment strategy alterations that impose a significant patient and healthcare burden. Intraoperative near infrared fluorescence (NIRF) imaging is one potential method to identify remaining tumor by visualization of NIR fluorophores that are preferentially localized to the tumor. This requires development of fluorophores that consistently identify tumor tissue in different patients and tumor types. In this study we examined a panel of NIRF contrast agents consisting of polymeric nanoparticle (NP) formulations derived from hyaluronic acid (HA), with either physically entrapped indocyanine green (ICG) or covalently conjugated Cy7.5. Using orthotopic human breast cancer MDA-MB-231 xenografts in nude mice we identified two lead formulations. One, NanoICGPBA, with physicochemically entrapped ICG, showed 2.3-fold greater tumor contrast than ICG alone at 24 h (p < 0.01), and another, NanoCy7.5100-H, with covalently conjugated Cy7.5, showed 74-fold greater tumor contrast than Cy7.5 alone at 24 h (p < 0.0001). These two lead formulations were then tested in immune competent BALB/c mice bearing orthotopic 4T1 breast cancer tumors. NanoICGPBA showed 2.2-fold greater contrast than ICG alone (p < 0.0001), and NanoCy7.5100-H showed 14.8-fold greater contrast than Cy7.5 alone (p < 0.0001). Furthermore, both NanoICGPBA and NanoCy7.5100-H provided strong tumor enhancement using image-guided surgery in mice bearing 4T1 tumors. These studies demonstrate the efficacy of a panel of HA-derived NPs in delineating tumors in vivo, and identifies promising formulations that can be used for future in vivo tumor removal efficacy studies. PMID:27877237

  7. Sensitive and rapid HPLC quantification of tenofovir from hyaluronic acid-based nanomedicine.

    PubMed

    Agrahari, Vivek; Youan, Bi-Botti C

    2012-03-01

    The purpose of this study was to develop and validate a rapid, sensitive, and specific reversed-phase high-performance liquid chromatography method for the quantitative determination of native tenofovir (TNF) for various applications. Different analytical performance parameters such as linearity, precision, accuracy, limit of quantification (LOQ), limit of detection (LOD), and robustness were determined according to International Conference on Harmonization (ICH) guidelines. A Bridge™ C18 column (150 × 4.6 mm, 5 μm) was used as stationary phase. The retention time of TNF was 1.54 ± 0.03 min (n = 6). The assay was linear over the concentration range of 0.1-10 μg/mL. The proposed method was sensitive with LOD and LOQ values equal to 50 and 100 ng/mL, respectively. The method was accurate with percent mean recovery from 95.41% to 102.90% and precise as percent RSD (relative standard deviation) values for intra-day, and inter-day precision were less than 2%. This method was utilized for the estimation of molar absorptivity of TNF at 259 nm (ε(259) = 12,518 L/mol/cm), calculated from linear regression analysis. The method was applied for determination of percentage of encapsulation efficiency (22.93 ± 0.04%), drug loading (12.25 ± 1.03%), in vitro drug release profile in the presence of enzyme (43% release in the first 3 h) and purification analysis of hyaluronic acid-based nanomedicine.

  8. Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule.

    PubMed

    Lee, Sang Gon; Jeong, Jae Han; Lee, Kyung Min; Jeong, Kyu Ho; Yang, Huisuk; Kim, Miroo; Jung, Hyungil; Lee, Sangkil; Choi, Young Wook

    2014-01-01

    Nanostructured lipid carriers (NLCs) were employed to formulate a lipophilic drug into hydrophilic polymeric microneedles (MNs). Hyaluronic acid (HA) was selected as a hydrophilic and bioerodible polymer to fabricate MNs, and nile red (NR) was used as a model lipophilic molecule. NR-loaded NLCs were consolidated into the HA-based MNs to prepare NLC-loaded MNs (NLC-MNs). A dispersion of NLCs was prepared by high-pressure homogenization after dissolving NR in Labrafil and mixing with melted Compritol, resulting in 268 nm NLCs with a polydispersity index of 0.273. The NLC dispersion showed a controlled release of NR over 24 hours, following Hixson-Crowell's cube root law. After mixing the NLC dispersion with the HA solution, the drawing lithography method was used to fabricate NLC-MNs. The length, base diameter, and tip diameter of the NLC-MNs were approximately 350, 380, and 30 μm, respectively. Fluorescence microscopic imaging of the NLC-MNs helped confirm that the NR-loaded NLCs were distributed evenly throughout the MNs. In a skin permeation study performed using a Franz diffusion cell with minipig dorsal skin, approximately 70% of NR was localized in the skin after 24-hour application of NLC-MNs. Confocal laser scanning microscopy (z-series) of the skin at different depths showed strong fluorescence intensity in the epidermal layer, which appeared to spread out radially with the passage of time. This study indicated that incorporation of drug-loaded NLCs into MNs could represent a promising strategy for controlled dermal delivery of lipophilic drugs.

  9. Hyaluronic acid enhancement of expanded polytetrafluoroethylene for small diameter vascular grafts

    NASA Astrophysics Data System (ADS)

    Lewis, Nicole R.

    Cardiovascular disease is the leading cause of mortality and morbidity in the United States and other developed countries. In the United States alone, 8 million people are diagnosed with peripheral arterial disease per year and over 250,000 patients have coronary bypass surgery each year. Autologous blood vessels are the standard graft used in small diameter (<6mm) arterial bypass procedures. Synthetic small diameter grafts have had limited success. While polyethylene (Dacron) and expanded polytetrafluoroethylene (ePTFE) are the most commonly used small diameter synthetic vascular graft materials, there are significant limitations that make these materials unfavorable for use in the low blood flow conditions of the small diameter arteries. Specifically, Dacron and ePTFE grafts display failure due to early thrombosis or late intimal hyperplasia. With the shortage of tissue donors and the limited supply of autologous blood vessels available, there is a need for a small diameter synthetic vascular graft alternative. The aim of this research is to create and characterize ePTFE grafts prepared with hyaluronic acid (HA), evaluate thrombogenic potential of ePTFE-HA grafts, and evaluate graft mechanical properties and coating durability. The results in this work indicate the successful production of ePTFE-HA materials using a solvent infiltration technique. Surface interactions with blood show increased platelet adhesion on HA-modified surfaces, though evidence may suggest less platelet activation and erythrocyte lysis. Significant changes in mechanical properties of HA-modified ePTFE materials were observed. Further investigation into solvent selection, uniformity of HA, endothelialization, and dynamic flow testing would be beneficial in the evaluation of these materials for use in small diameter vascular graft bypass procedures.

  10. Extended release of hyaluronic acid from hydrogel contact lenses for dry eye syndrome.

    PubMed

    Maulvi, Furqan A; Soni, Tejal G; Shah, Dinesh O

    2015-01-01

    Current dry eye treatment includes delivering comfort enhancing agents to the eye via eye drops, but low residence time of eye drops leads to low bioavailability. Frequent administration leads to incompliance in patients, so there is a great need for medical device such as contact lenses to treat dry eye. Studies in the past have demonstrated the efficacy of hyaluronic acid (HA) in the treatment of dry eyes using eye drops. In this paper, we present two methods to load HA in hydrogel contact lenses, soaking method and direct entrapment. The contact lenses were characterized by studying their optical and physical properties to determine their suitability as extended wear contact lenses. HA-laden hydrogel contact lenses prepared by soaking method showed release up to 48 h with acceptable physical and optical properties. Hydrogel contact lenses prepared by direct entrapment method showed significant sustained release in comparison to soaking method. HA entrapped in hydrogels resulted in reduction in % transmittance, sodium ion permeability and surface contact angle, while increase in % swelling. The impact on each of these properties was proportional to HA loading. The batch with 200-μg HA loading showed all acceptable values (parameters) for contact lens use. Results of cytotoxicity study indicated the safety of hydrogel contact lenses. In vivo pharmacokinetics studies in rabbit tear fluid showed dramatic increase in HA mean residence time and area under the curve with lenses in comparison to eye drop treatment. The study demonstrates the promising potential of delivering HA through contact lenses for the treatment of dry eye syndrome.

  11. Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

    SciTech Connect

    Chapet, Olivier; Decullier, Evelyne; Bin, Sylvie; Faix, Antoine; Ruffion, Alain; Jalade, Patrice; Fenoglietto, Pascal; Udrescu, Corina; Enachescu, Ciprian; Azria, David

    2015-03-15

    Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.

  12. Unraveling the confusion behind hyaluronic acid efficacy in the treatment of symptomatic knee osteoarthritis

    PubMed Central

    Miller, Larry E; Altman, Roy D; McIntyre, Louis F

    2016-01-01

    Hyaluronic acid (HA) is a commonly prescribed treatment for knee pain resulting from osteoarthritis (OA). Although numerous HA products have been approved for use by the US Food and Drug Administration, the efficacy of HA injections for knee OA remains disputed with meta-analyses and societal clinical guidelines drawing disparate conclusions. The American Academy of Orthopaedic Surgeons (AAOS) recently published a best-evidence systematic review and concluded that available data did not support the routine use of HA for knee OA. The purpose of the current article is to highlight issues that confound interpretation of meta-analyses on HA for knee OA, to provide realistic estimates of the true efficacy of HA injections in knee OA, and to provide commentary on the methods and conclusions from the AAOS systematic review. In general, the clinical benefit of HA is underestimated using conventional meta-analytic techniques. When accounting for differential control group effects in HA studies, it can be reasonably concluded that HA injections may be beneficial to an appreciable number of patients with knee OA. In addition, the systematic review methodology used by AAOS was questionable due to exclusion of numerous relevant studies and inclusion of studies that used HAs not approved for use in the US, both of which underestimated the true efficacy of HA injections. Overall, the efficacy of HA injections for knee OA is likely better than previously reported. Future clinical trials and meta-analyses should account for differential control group effects in order to avoid the continued confusion surrounding HA injection efficacy. PMID:27382328

  13. Receptor for Hyaluronic Acid-Mediated Motility is Associated with Poor Survival in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Cheng, Xiao-Bo; Sato, Norihiro; Kohi, Shiro; Koga, Atsuhiro; Hirata, Keiji

    2015-01-01

    Receptor for hyaluronic acid (HA)-mediated motility (RHAMM) is a nonintegral cell surface receptor involved in the aggressive phenotype in a wide spectrum of human malignancies, but the significance of RHAMM in pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, we investigated the expression of RHAMM and its clinical relevance in PDAC. RHAMM mRNA expression was examined in 8 PDAC cell lines and in primary pancreatic cancer and adjacent non-tumor tissues from 14 patients using real-time RT-PCR. Western blotting was carried out to analyze the expression of RHAMM protein in PDAC cell lines. We also investigated the expression patterns of RHAMM protein in tissue samples from 70 PDAC patients using immunohistochemistry. The RHAMM mRNA expression was increased in some PDAC cell lines as compared to a non-tumorous pancreatic epithelial cell line HPDE. The RHAMM mRNA expression was significantly higher in PDAC tissues as compared to corresponding non-tumorous pancreatic tissues (P < 0.0001). The RHAMM protein expression was higher in the vast majority of PDAC cell lines relative to the expression in HPDE. The immunohistochemical analysis revealed strong expression of RHAMM in 52 (74%) PDAC tissues. Strong expression of RHAMM was significantly associated with a shorter survival time (P = 0.038). In multivariate analysis, tumor stage (P = 0.039), residual tumor (P = 0.015), and strong RHAMM expression (P = 0.034) were independent factors predicting poor survival. Strong expression of RHAMM may predict poor survival in PDAC patients and may provide prognostic and, possibly, therapeutic value. PMID:26516356

  14. Clinical Evaluation of Hyaluronic Acid Sponge with Zinc versus Placebo for Scar Reduction after Breast Surgery

    PubMed Central

    Mahedia, Monali; Shah, Nilay

    2016-01-01

    Background: Scar formation is a major source of dissatisfaction among patients and surgeons. Individually, hyaluronan, or hyaluronic acid (HA), and zinc have been shown to reduce scarring. The authors evaluated the safety and efficacy of an HA sponge with zinc compared with placebo when applied to bilateral breast surgery scars; specifically, they evaluated whether the use of this product modulates inflammation and immediate scarring in treated patients after bilateral breast surgery. Methods: This double-blind, randomized, prospective study was approved by the local institutional review board. Bilateral breast surgery patients with right and left incision lines were randomly assigned to receive HA sponge with zinc or placebo within 2 to 4 days after their procedure. Participants were followed up at 6 weeks, 12 weeks, and 1 year and evaluated at 12 weeks. Three blinded evaluators reviewed photographs of the incision lines and assessed the scars using a visual analog scale, new scale, and a patient satisfaction survey. Results: Nineteen bilateral breast surgery patients were enrolled in the study. Statistical analysis was performed on 14 patients who completed the follow-up. The mean visual analog scale score was lower for the side receiving the HA sponge with zinc (2.6) than for the side receiving placebo (3.0), indicating a better outcome (t test; P = 0.08). The HA sponge with zinc was found to have significant positive findings on a patient satisfaction survey (P = 0.01). Conclusions: This is a preliminary study that shows zinc hyaluronan was associated with high patient satisfaction in achieving a better scar after bilateral breast surgery, irrespective of skin color. It seems to be safe and effective for early scars. PMID:27536470

  15. Enhancing neural stem cell response to SDF-1α gradients through hyaluronic acid-laminin hydrogels.

    PubMed

    Addington, C P; Heffernan, J M; Millar-Haskell, C S; Tucker, E W; Sirianni, R W; Stabenfeldt, S E

    2015-12-01

    Traumatic brain injury (TBI) initiates an expansive biochemical insult that is largely responsible for the long-term dysfunction associated with TBI; however, current clinical treatments fall short of addressing these underlying sequelae. Pre-clinical investigations have used stem cell transplantation with moderate success, but are plagued by staggeringly low survival and engraftment rates (2-4%). As such, providing cell transplants with the means to better dynamically respond to injury-related signals within the transplant microenvironment may afford improved transplantation survival and engraftment rates. The chemokine stromal cell-derived factor-1α (SDF-1α) is a potent chemotactic signal that is readily present after TBI. In this study, we sought to develop a transplantation vehicle to ultimately enhance the responsiveness of neural transplants to injury-induced SDF-1α. Specifically, we hypothesize that a hyaluronic acid (HA) and laminin (Lm) hydrogel would promote 1. upregulated expression of the SDF-1α receptor CXCR4 in neural progenitor/stem cells (NPSCs) and 2. enhanced NPSC migration in response to SDF-1α gradients. We demonstrated successful development of a HA-Lm hydrogel and utilized standard protein and cellular assays to probe NPSC CXCR4 expression and NPSC chemotactic migration. The findings demonstrated that NPSCs significantly increased CXCR4 expression after 48 h of culture on the HA-Lm gel in a manner critically dependent on both HA and laminin. Moreover, the HA-Lm hydrogel significantly increased NPSC chemotactic migration in response to SDF-1α at 48 h, an effect that was critically dependent on HA, laminin and the SDF-1α gradient. Therefore, this hydrogel serves to 1. prime NPSCs for the injury microenvironment and 2. provide the appropriate infrastructure to support migration into the surrounding tissue, equipping cells with the tools to more effectively respond to the injury microenvironment.

  16. Characterization of hyaluronic acid and synovial fluid in stagnation point elongational flow.

    PubMed

    Haward, Simon J

    2014-03-01

    Hyaluronic acid (HA) is an important biomacromolecule, which fulfils a number of vital physiological functions (especially in the joint synovial fluid) and also has consumer and pharmaceutical applications. HA solution properties have already been quite thoroughly characterized in response to steady shear flows but are less well understood in highly deforming extensional flows. In this study, flow-induced birefringence measurements are made as a function of the strain rate in planar elongational flow at the stagnation point of a cross-slot device using HA solutions of a range of molecular weights (0.9×10(6) g mol(-1)≤Mw≤4.8×10(6) g mol(-1)) and at dilute concentrations. The results provide macromolecular relaxation times, molecular weight distributions and the extensional viscosities and Trouton ratios of the fluids. The HA relaxation time is found to vary as τ∼Mw1.8, which is consistent with a partially solvated, expanded coil. An intrinsic Trouton ratio is defined, which varies as [Tr]∼Mw2. The measurement of birefringence with strain rate is shown to be highly sensitive to the molecular weight distribution and can resolve subtle changes due to macromolecular degradation and the presence of fracture products. Mechanical degradation experiments in the cross-slots indicate midchain scission of HA macromolecules, strongly suggesting near full extension of the high-molecular weight fraction in the stagnation point extensional flow field. Taken together the results suggest a possible method for analysis of the HA in synovial fluid, and this concept is tested using synovial fluid obtained from porcine tarsal joint.

  17. Extensional flow of hyaluronic acid solutions in an optimized microfluidic cross-slot device.

    PubMed

    Haward, S J; Jaishankar, A; Oliveira, M S N; Alves, M A; McKinley, G H

    2013-07-01

    We utilize a recently developed microfluidic device, the Optimized Shape Cross-slot Extensional Rheometer (OSCER), to study the elongational flow behavior and rheological properties of hyaluronic acid (HA) solutions representative of the synovial fluid (SF) found in the knee joint. The OSCER geometry is a stagnation point device that imposes a planar extensional flow with a homogenous extension rate over a significant length of the inlet and outlet channel axes. Due to the compressive nature of the flow generated along the inlet channels, and the planar elongational flow along the outlet channels, the flow field in the OSCER device can also be considered as representative of the flow field that arises between compressing articular cartilage layers of the knee joints during running or jumping movements. Full-field birefringence microscopy measurements demonstrate a high degree of localized macromolecular orientation along streamlines passing close to the stagnation point of the OSCER device, while micro-particle image velocimetry is used to quantify the flow kinematics. The stress-optical rule is used to assess the local extensional viscosity in the elongating fluid elements as a function of the measured deformation rate. The large limiting values of the dimensionless Trouton ratio, Tr ∼ O(50), demonstrate that these fluids are highly extensional-thickening, providing a clear mechanism for the load-dampening properties of SF. The results also indicate the potential for utilizing the OSCER in screening of physiological SF samples, which will lead to improved understanding of, and therapies for, disease progression in arthritis sufferers.

  18. Viscosupplementation with intra-articular hyaluronic acid for treatment of osteoarthritis in the elderly.

    PubMed

    Abate, M; Pulcini, D; Di Iorio, A; Schiavone, C

    2010-01-01

    Osteoarthritis (OA) is very disabling condition in the elderly. The current therapeutic approaches (analgesics, NSAIDs, COX-2 inhibitors, steroids) do not delay the OA progression or reverse joint damage. Moreover, they may cause relevant systemic side effects. Hyaluronic acid (HA) is a physiologic component of the synovial fluid and is reduced in OA joints. Therefore, intra-articular injection of HA, due to its viscoelastic properties and protective effect on articular cartilage and soft tissue surfaces of joints, can restore the normal articular homoeostasis. These effects are evident when HA is properly administered into the articular space; therefore, the use of "image-guided" infiltration techniques is mandatory. Viscosupplementation (VS), with different HA preparations (Low and High molecular weight), can be considered when the patient has not found pain relief from other therapies or is intolerant to analgesics or NSAIDs. A 3-5 doses regimen is usually recommended with 1 week interval between each injection. Several studies have shown the efficacy of HA for the treatment of knee OA, with positive effects on pain, articular function (Western Ontario and Mc Master Universities Osteoarthritis Index [WOMAC], Lequesne Index [LI], Range of Motion [ROM]), subjective global assessment and reduction in NSAIDs consumption. In general, the benefit is evident within 3 months and persists in the following 6-12 months. Encouraging but inconclusive results have also been observed for the treatment of shoulder, carpo-metacarpal, hip and ankle OA. However there is the need of better designed studies to prove the effectiveness of these medications, in order to rule out a placebo effect. The therapy is well tolerated with absence of systemic side effects and only with limited local discomfort.

  19. [Cost-analysis of viscosupplementation treatment with hyaluronic acid in candidate knee replacement patients with osteoarhritis].

    PubMed

    Mar, J; Romero Jurado, M; Arrospide, A; Enrique Fidalgo, A; Soler López, B

    2013-01-01

    A high percentage of knee osteoarthritis finally need a knee replacement. Previous treatments used including viscosupplementation with hyaluronic acid can delay the knee replacement. The objective of this study was to estimate the economic impact in the short, medium and long term of the knee replacement delay, by conducting a budget impact analysis of the incorporation of viscosupplementation to the treatment of knee osteoarthritis. From the data of patients treated at a specialized Knee Osteoarthritis Unit we built a discrete event simulation model that reproduced the progress of patients, as it could represent changes in the health status of an individual and their interaction with the system. The model allowed the number of prostheses and replacements performed each year to be calculated in a population including 1,000 patients each year according to the use of viscosupplementation. The budget impact analysis was estimated for 10 years by adding the cost of each treatment. A total of 224 patient candidates to receive a knee replacement were studied. The viscosupplementation use delayed the need to perform the knee replacement by 2.67 years The budgetary impact would lead to net savings during the 10 years. However, it is much greater in the earlier years. The sum of the savings in the first three years would be 36 million euros. The study concludes that the use of viscosupplementation reduced the economic burden of knee osteoarthritis in the health system as a result of delayed knee replacement. The simulation model enabled the economic impact in both the short and long term to be analysed.

  20. Development of chitosan nanoparticles coated with hyaluronic acid for topical ocular delivery of dexamethasone.

    PubMed

    Kalam, Mohd Abul

    2016-08-01

    The present study involved design of dexamethasone-sodium phosphate (DEX) loaded mucoadhesive chitosan nanoparticles for topical ocular delivery to improve its precorneal retention and corneal permeability. The chitosan-sodium tripolyphosphate nanoparticle (CS-NPs) was developed through ionotropic-gelation technique. The developed CS-NPs were coated with hyaluronic-acid (HA) to make discrete, free-flowing NPs and to improve their mucoadhesive characteristics. The particle-size, zeta-potential and polydispersity-index were determined by Malvern-Zetasizer. The average size of the CS-NPs ranged from 305.25±14.29nm (without HA-coating and before freeze-drying) to 400.57±15.23nm (HA-coated and after freeze-drying). Due to the polyanionic nature of HA, reversing of zeta-potentials from +32.55±4.15 to -33.74±3.45 was observed. Polydispersity-indices varied from 0.178±0.067 (before freeze-drying of HA-coated F2) to 0.427±0.028 (after freeze-drying of HA-coated F2). The encapsulation and loading capacity of around 72.95% and 14.51% respectively were found in optimized CS-NPs. In simulated tear fluid 75.84% cumulative amount of released drug was detected and the in-vitro release results suggested the mechanism of drug release was Fickian-diffusion type. The clarity, pH, refractive index, surface tension and viscosity of the suspensions of DEX-CS-NPs were found promising for ocular use. Stability study on nanoparticles revealed no significant changes were observed in particle-size, encapsulation, drug release and physicochemical characteristics at 25°C for 3-months storage.

  1. Hyaluronic acid embedded cellulose acetate phthlate core/shell nanoparticulate carrier of 5-fluorouracil.

    PubMed

    Garg, Ashish; Rai, Gopal; Lodhi, Santram; Jain, Alok Pal; Yadav, Awesh K

    2016-06-01

    Aim of this research was to prepare hyaluronic acid-modified-cellulose acetate phthalate (HAC) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). HAC copolymer was synthesized and confirmed by fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. HAC NPs with 5-FU were prepared using HAC copolymer and compared with 5-FU loaded cellulose acetate phthalate (CAP) NPs. NPs were characterized by atomic force microscopy (AFM), particle size, zeta potential, polydispersity index, entrapment efficiency, in-vitro release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). HAC NPs were found slower release (97.30% in 48h) than (99.25% in 8h) CAP NPs. In cytotoxicity studies, showed great cytotoxic potential of 5-FU loaded HAC NPs in A549, MDA-MD-435 and SK-OV-3 cancer cellline. HAC NPs showing least hemolytic than CAP NPs and 5-FU. Area under curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and time to reach maximum plasma concentration Tmax), were observed 4398.1±7.90μgh/mL, 145.45±2.25μg/L, 45.74±0.25h, 72±0.50h, respectively of HAC NPs and 119.92±1.78μgh/mL, 46.38±3.42μg/L, 1.2±0.25h, 0.5±0.02h were observed in plain 5-FU solution. In conclusion, HAC NPs is effective deliver carrier of 5-FU for lung cancer.

  2. Nanotubes-Embedded Indocyanine Green-Hyaluronic Acid Nanoparticles for Photoacoustic-Imaging-Guided Phototherapy.

    PubMed

    Wang, Guohao; Zhang, Fan; Tian, Rui; Zhang, Liwen; Fu, Guifeng; Yang, Lily; Zhu, Lei

    2016-03-02

    Phototherapy is a light-triggered treatment for tumor ablation and growth inhibition via photodynamic therapy (PDT) and photothermal therapy (PTT). Despite extensive studies in this area, a major challenge is the lack of selective and effective phototherapy agents that can specifically accumulate in tumors to reach a therapeutic concentration. Although recent attempts have produced photosensitizers complexed with photothermal nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy still hampers the broad utilization of these nanocarriers. Herein, we developed a CD44 targeted photoacoustic (PA) nanophototherapy agent by conjugating Indocyanine Green (ICG) to hyaluronic acid nanoparticles (HANPs) encapsulated with single-walled carbon nanotubes (SWCNTs), resulting in a theranostic nanocomplex of ICG-HANP/SWCNTs (IHANPT). We fully characterized its physical features as well as PA imaging and photothermal and photodynamic therapy properties in vitro and in vivo. Systemic delivery of IHANPT theranostic nanoparticles led to the accumulation of the targeted nanoparticles in tumors in a human cancer xenograft model in nude mice. PA imaging confirmed targeted delivery of the IHANPT nanoparticles into tumors (T/M ratio = 5.19 ± 0.3). The effect of phototherapy was demonstrated by low-power laser irradiation (808 nm, 0.8 W/cm(2)) to induce efficient photodynamic effect from ICG dye. The photothermal effect from the ICG and SWCNTs rapidly raised the tumor temperature to 55.4 ± 1.8 °C. As the result, significant tumor growth inhibition and marked induction of tumor cell death and necrosis were observed in the tumors in the tumors. There were no apparent systemic and local toxic effects found in the mice. The dynamic thermal stability of IHANPT was studied to ensure that PTT does not affect ICG-dependent PDT in phototherapy. Therefore, our results highlight imaging property and therapeutic effect of the novel IHANPT theranostic nanoparticle for CD44

  3. Novel hyaluronic acid-chitosan nanoparticles as non-viral gene delivery vectors targeting osteoarthritis.

    PubMed

    Lu, Hua-Ding; Zhao, Hui-Qing; Wang, Kun; Lv, Lu-Lu

    2011-11-28

    Gene therapy is a promising new treatment strategy for common joint-disorders such as osteoarthritis. The development of safe, effective, targeted non-viral gene carriers is important for the clinical success of gene therapy. The present work describes the use of hybrid hyaluronic acid (HA)/chitosan (CS) nanoparticles as novel non-viral gene delivery vectors capable of transferring exogenous genes into primary chondrocytes for the treatment of joint diseases. HA/CS plasmid-DNA nanoparticles were synthesized through the complex coacervation of the cationic polymers with pEGFP. Particle size and zeta potential were related to the weight ratio of CS to HA, where increases in nanoparticle size and decreases in surface charge were observed as HA content increased. The particle size and the zeta potential varied according to pH. Transfection of primary chondrocytes was performed under different conditions to examine variations in the pH of the transfection medium, different N/P ratios, different plasmid concentrations, and different molecular weights of chitosan. Transfection efficiency was maximized for a medium pH of approximately 6.8, an N/P ratio of 5, plasmid concentration of 4 μg/ml, and a chitosan molecular weight of 50 kDa. The transfection efficiency of HA/CS-plasmid nanoparticles was significantly higher than that of CS-plasmid nanoparticles under the same conditions. The average viability of cells transfected with HA/CS-plasmid nanoparticles was over 90%. These results suggest that HA/CS-plasmid nanoparticles could be an effective non-viral vector suitable for gene delivery to chondrocytes.

  4. The effects of hyaluronic acid on hemiplegic shoulder injury and pain in patients with subacute stroke

    PubMed Central

    Huang, Yu-Chi; Leong, Chau-Peng; Wang, Lin; Chen, Mei-Ju; Chuang, Chien-Yi; Liaw, Mei-Yun; Wang, Lin-Yi

    2016-01-01

    Abstract Background: Hemiplegic shoulder pain (HSP) is one of the most common comorbidities in stroke patients with flaccid shoulders. The pain limits functional motor recovery and affects the activities of daily living after acute stroke. This study investigated the effects of hyaluronic acid (HA) injection on pain reduction and motor function in subacute stroke patients with HSP and injury. Methods: A randomized, double-blinded controlled trial was conducted in a medical center. Twenty-six subacute stroke patients were enrolled and randomly divided into 2 groups: the experimental group (n = 16) received ultrasound-guided, subacromial HA injections once per week for 3 weeks and conventional rehabilitation, whereas the control group (n = 10) received 0.9% sodium chloride injections once per week for 3 weeks and conventional rehabilitation. Shoulder pain and motor function were evaluated before and after the intervention using the visual analog scale (VAS) and the Fugl–Meyer assessment for the upper extremity (FMA-UE), respectively. Results: In the experimental group, significant differences were found in VAS (P = 0.003), shoulder flexion (P = 0.03) and abduction (P = 0.02), and FMA-UE (P = 0.003) after treatment. In the control group, there were significant differences in VAS (P = 0.007), shoulder flexion (P = 0.035), and FMA-UE (P = 0.042) after treatment. The comparison of the changes in the parameters between the experimental and control groups, after each intervention, revealed a significant difference in VAS (P = 0.001). Conclusion: Subacromial HA injection could result in positive effects on shoulder pain and shoulder abduction in subacute stroke patients with HSP and injury. PMID:27930553

  5. Hyaluronic acid enhances the mechanical properties of tissue-engineered cartilage constructs.

    PubMed

    Levett, Peter A; Hutmacher, Dietmar W; Malda, Jos; Klein, Travis J

    2014-01-01

    There is a need for materials that are well suited for cartilage tissue engineering. Hydrogels have emerged as promising biomaterials for cartilage repair, since, like cartilage, they have high water content, and they allow cells to be encapsulated within the material in a genuinely three-dimensional microenvironment. In this study, we investigated the mechanical properties of tissue-engineered cartilage constructs using in vitro culture models incorporating human chondrocytes from osteoarthritis patients. We evaluated hydrogels formed from mixtures of photocrosslinkable gelatin-methacrylamide (Gel-MA) and varying concentrations (0-2%) of hyaluronic acid methacrylate (HA-MA). Initially, only small differences in the stiffness of each hydrogel existed. After 4 weeks of culture, and to a greater extent 8 weeks of culture, HA-MA had striking and concentration dependent impact on the changes in mechanical properties. For example, the initial compressive moduli of cell-laden constructs with 0 and 1% HA-MA were 29 and 41 kPa, respectively. After 8 weeks of culture, the moduli of these constructs had increased to 66 and 147 kPa respectively, representing a net improvement of 69 kPa for gels with 1% HA-MA. Similarly the equilibrium modulus, dynamic modulus, failure strength and failure strain were all improved in constructs containing HA-MA. Differences in mechanical properties did not correlate with glycosaminoglycan content, which did not vary greatly between groups, yet there were clear differences in aggrecan intensity and distribution as assessed using immunostaining. Based on the functional development with time in culture using human chondrocytes, mixtures of Gel-MA and HA-MA are promising candidates for cartilage tissue-engineering applications.

  6. Protein adsorption, fibroblast activity and antibacterial properties of poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) grafted with chitosan and chitooligosaccharide after immobilized with hyaluronic acid.

    PubMed

    Hu, S-G; Jou, C-H; Yang, M C

    2003-07-01

    Poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) membrane was treated with ozone and grafted with acrylic acid. The resulting membranes were further grafted with chitosan (CS) or chitooligosaccharide (COS) via esterification. Afterward hyaluronic acid (HA) was immobilized onto CS- or COS-grafting membranes. The antibacterial activity of CS and COS against Staphylococus aureus, Escherichia coli, and Pseudomonas aeruginosa was preserved after HA immobilization. Among them, CS-grafted PHBV membrane showed higher antibacterial activity than COS-grafted PHBV membrane. In addition, after CS- or COS-grafting, the L929 fibroblasts attachment and protein adsorption were improved, while the cell number was decrease. After immobilizing HA, the cell proliferation was promoted, the protein adsorption was decreased, and the cell attachment was slightly lower than CS- or COS-grafting PHBV.

  7. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery.

    PubMed

    Nasr, Maha

    2016-05-01

    The development of mucoadhesive lipidic nanoemulsion based on hyaluronic acid, co-encapsulating two polyphenols (resveratrol and curcumin) for the transnasal treatment of neurodegenerative diseases was attempted in the current manuscript. Nanoemulsions were prepared by the spontaneous emulsification method, and were characterized for their particle size, zeta potential, mucoadhesive strength and morphology. The selected formula was tested for its antioxidant potential, in vitro and ex vivo release of the two polyphenols, safety on nasal mucosa and in vivo quantification of the two drugs in rat brains. Its stability was tested by monitoring the change in particle size, zeta potential, drugs' content and antioxidant potential upon storage for 3 months. The optimized hyaluronic acid based nanoemulsion formula displayed a particle size of 115.2 ± 0.15 and a zeta potential of -23.9 ± 1.7. The formula displayed a spherical morphology and significantly higher mucoadhesive strength compared to its non mucoadhesive counterpart. In addition, the nanoemulsion was able to preserve the antioxidant ability of the two polyphenols and protect them from degradation. Diffusion controlled release of the two drugs was achievable till 6 hours, with an ex vivo flux across sheep nasal mucosa of 2.86 and 2.09 µg/cm(2)hr for resveratrol and curcumin, respectively. Moreover, the mucoadhesive nanoemulsion was safe on nasal mucosa and managed to increase the amounts of the two polypehnols in the brain (about 7 and 9 folds increase in AUC0-7 h for resveratrol and curcumin, respectively). Hyaluronic acid based lipidic nanoemulsion proved itself as a successful carrier enhancing the solubility, stability and brain targetability of polyphenols.

  8. Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation.

    PubMed

    Ravar, Fatemeh; Saadat, Ebrahim; Gholami, Mehdi; Dehghankelishadi, Pouya; Mahdavi, Mehdi; Azami, Samira; Dorkoosh, Farid A

    2016-05-10

    Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy.

  9. Global Aesthetics Consensus: Hyaluronic Acid Fillers and Botulinum Toxin Type A—Recommendations for Combined Treatment and Optimizing Outcomes in Diverse Patient Populations

    PubMed Central

    Liew, Steven; Signorini, Massimo; Vieira Braz, André; Fagien, Steven; Swift, Arthur; De Boulle, Koenraad L.; Raspaldo, Hervé; Trindade de Almeida, Ada R.; Monheit, Gary

    2016-01-01

    Background: Combination of fillers and botulinum toxin for aesthetic applications is increasingly popular. Patient demographics continue to diversify, and include an expanding population receiving maintenance treatments over decades. Methods: A multinational panel of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group to develop updated guidelines with a worldwide perspective for hyaluronic acid fillers and botulinum toxin. This publication considers strategies for combined treatments, and how patient diversity influences treatment planning and outcomes. Results: Global Aesthetics Consensus Group recommendations reflect increased use of combined treatments in the lower and upper face, and some midface regions. A fully patient-tailored approach considers physiologic and chronologic age, ethnically associated facial morphotypes, and aesthetic ideals based on sex and culture. Lower toxin dosing, to modulate rather than paralyze muscles, is indicated where volume deficits influence muscular activity. Combination of toxin with fillers is appropriate for several indications addressed previously with toxin alone. New scientific data regarding hyaluronic acid fillers foster an evidence-based approach to selection of products and injection techniques. Focus on aesthetic units, rather than isolated rhytides, optimizes results from toxin and fillers. It also informs longitudinal treatment planning, and analysis of toxin nonresponders. Conclusions: The emerging objective of injectable treatment is facial harmonization rather than rejuvenation. Combined treatment is now a standard of care. Its use will increase further as we refine the concept that aspects of aging are intimately related, and that successful treatment entails identifying and addressing the primary causes of each. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID:27119917

  10. Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (hylaform from rooster combs and restylane from streptococcus) used for soft tissue augmentation.

    PubMed

    Manna, F; Dentini, M; Desideri, P; De Pità, O; Mortilla, E; Maras, B

    1999-11-01

    Hyaluronic acid (HA) derivatives have been developed to try to enhance rheological properties of this molecule to make it suitable for various medical applications. The main dermatological application of HA derivatives is the augmentation of soft tissues, via injection into the dermis. HA derivatives are indicated for the correction of cutaneous contour deficiencies of the skin, particularly in cases of ageing or degenerative lesions or to increase lips. Two HA derivatives have been evaluated: Hylaform Viscoelastic Gel (Hylan B), derived from rooster combs and subjected to cross-linking, and Restylane, produced through bacterial fermentation (streptococci) and stabilized, as declared by the producer. In both cases the purpose is to improve HA theological characteristics and slow down its degradation once it is in contact with biological structures. Distribution of particle dimensions, pH, protein concentration and rheological properties have been investigated in order to evaluate their reliability as fillers for soft tissue augmentation. The results of the analyses showed that there are differences between Restylane and Hylaform. Especially as far as rheological characteristics are concerned, the results outline different structures of the products: Hylaform behaves as a strong hydrogel, Restylane as a weak hydrogel; rheologically Hylaform is clearly superior to Restylane. Hylaform contains a definitely minor quantity (about a quarter) of cross-linked hyaluronic acid than Restylane. Furthermore, although not declared by the manufacturer, Restylane contains protein, resulting from bacterial fermentation or added to enable cross-linking reaction; the quantity of proteins contained by Restylane can be as much as four times the quantity contained by Hylaform, for the same volume (1 ml). It is evident that Hylaform offers higher safety margin than Restylane. Furthermore, wide literature and 20 years of clinical experience on hyaluronan derived from rooster combs confirm

  11. Hyaluronic acid immobilization on the poly-allylamine coated nano-network TiO2 surface.

    PubMed

    Shim, Jae-Won; Lee, Kang; Jeong, Moon-Jin; Jung, Sang-Chul; Kim, Byung-Hoon

    2011-08-01

    Recently, biocompatibility report revealed that the TiO2 nano-network (TiO2 NT) structure has much higher cells colonization than the native TiO2 on Ti surface. In this study, we prepared the hyaluronic acid (HA) immobilized TiO2 NT layer by plasma surface modification and then evaluated biological behavior of MC3T3-E1 on the Ti, TiO2 NT and TiO2 NT/NH2/HA surface. The cell viability tests revealed slightly enhanced viability on the TiO2 NT/NH2/HA surfaces than on the untreated Ti surfaces.

  12. Viscosupplementation with hyaluronic acid in the treatment for cartilage lesions: a review of current evidence and future directions.

    PubMed

    Clegg, Travis E; Caborn, David; Mauffrey, Cyril

    2013-02-01

    Diseases involving the articular cartilage are one of the leading causes of physical impairment among the adult population. While surgical technique and advancement have allowed us effective means at treating these diseases, this is not without significant risk and morbidity. With a very solid safety profile, viscosupplementation with hyaluronic acid (HA) derivatives has become an excellent modality for treating diseased articular cartilage. Recent literature supports the use of HA not only in the management of the pain associated with osteoarthritis but also as a disease-modifying agent as well. Further studies have started to define exciting new roles for viscosupplementation in the treatment for acute injuries to the joint microenvironment.

  13. [The noninvasive evaluation of degree of expression of fibrosis of liver and significance of polymorphism of gene of hyaluronic acid under chronic hepatitis C].

    PubMed

    Bulatova, I A; Schekotova, A P; Krivtsov, A V; Schekotov, V V; Pavlov, A I

    2015-03-01

    The study was carries out to evaluate degree of expression of fibrosis, reparation processes in liver and value of polymorphism of gene of hyaluronic acid HASI (rs11084111) in progression of affection of liver in patients with chronic hepatitis C. The sampling included 100 patients with chronic hepatitis C. The control group included 83 healthy donors. The blood serum was tested to detect concentration of hyaluronic acid and alpha-fetoprotein. The stage of liver fibrosis (F) was evaluated by using ultrasound fibroflexography The polymorphism of gene (rs11084111) was analysed by polymerase chain reaction technique. In the group of patients with F1 the average concentration of hyaluronic acid in blood serum in 1.8 times surpassed this indicator in group with F0. The concentration of hyaluronic acid was almost 2 times higher under F3 as compared with F1-F2. This indicator permitted differentiating F3 and F4 which followed by activation of cytolysis and cholestasis in F1 and F3 and by increasing of level of alpha-fetoprotein at stages F1 and F4. The study detected no statistically significant difference between rates of genotypes and alleles of gene HASI (rs11084111) in groups of healthy patients and patients with chronic hepatitis C. The direct relationships are established between hyaluronic acid and markers of cytolysis, cholestasis, alpha-fetoprotein (p = 0.001), viral load (p = 0.003) liver elasticity index according fibroflexography data (p < 0.001) and fibrosis index (p < 0.001). The established relationships indicate association of hepatofibrosis with cytolysis, cholestasis, hepatocytes regeneration and virus activity. The hyaluronic acid permits to stratify minimal expressed fibrosis and also the transition of disease to the stage of cirrhosis.

  14. Targeting hyaluronic acid production for the treatment of leukemia: treatment with 4-methylumbelliferone leads to induction of MAPK-mediated apoptosis in K562 leukemia.

    PubMed

    Uchakina, Olga N; Ban, Hao; McKallip, Robert J

    2013-10-01

    The current study examined the effect of modulation of hyaluronic acid (HA) synthesis on leukemia cell survival using the hyaluronic acid synthesis inhibitor 4-methylumbelliferone (4-MU). Treatment of CML cells with 4-MU led to caspase-dependent apoptosis characterized by decreased HA production, PARP cleavage, and increased phosphorylation of p38. Addition of exogenous HA, the pan caspase inhibitor Z-VAD-FMK or the p38 inhibitor SB203580 to 4-MU treated cells was able to protect cells from apoptosis. Treatment of tumor-bearing mice with 4-MU led to a significant reduction in tumor load which was mediated through the induction of apoptosis.

  15. Evaluation of intra-articular delivery of hyaluronic acid functionalized biopolymeric nanoparticles in healthy rat knees.

    PubMed

    Zille, Hervé; Paquet, Joseph; Henrionnet, Christel; Scala-Bertola, Julien; Leonard, Michèle; Six, Jean Luc; Deschamp, Frantz; Netter, Patrick; Vergès, José; Gillet, Pierre; Grossin, Laurent

    2010-01-01

    The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to assess the effects and localization of the nanocapsules in the knee joint. We did not observe significant modifications in the synovial membranes (weak hyperplasia) or patellae integrity after local administration of nanodevices into the rats. While we found some nanoparticles in the synovial membrane, none were detected in the patellae. Moreover, the histological observations for patellae were confirmed by radiosulfate intake, which depicted no decrease in proteoglycans biosynthesis in nanoparticles treated animals. Concerning the safety towards synovial membranes, we also had a look at the inflammatory response after injections of nanoparticles covered by amphiphilic HA or polyvinyl alcohol (PVA) by monitoring the mRNA expression levels of some specific early cytokines (IL-1β and TNF-α). Once again, no differences were observed between the control rats and the rats treated with nanoparticles. Considering these preliminary results obtained in healthy rats, we can establish that

  16. Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

    SciTech Connect

    Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

    1989-04-01

    We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that in control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.

  17. Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

    PubMed

    Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

    2015-01-01

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

  18. Hyaluronic acid and glucosamine sulfate for adult Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

    PubMed

    Xia, Chuan-Tao; Yu, Fang-Fang; Ren, Feng-Ling; Fang, Hua; Guo, Xiong

    2016-05-01

    To evaluate the efficacy and safety of hyaluronic acid (HA) and glucosamine sulfate (GS) in alleviating symptoms and improving function of Kashin-Beck disease (KBD). A cluster-randomized, placebo-controlled trial was conducted in 150 patients with KBD. Participants were randomly allocated to receive intra-articular injection hyaluronic acid (IAHA) for 4 weeks, oral GS for 12 weeks, or oral placebo for 12 weeks. The primary outcome measures were 20 % and 50 % reductions in pain from baseline measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. Secondary outcome measures included WOMAC index parameters of pain, stiffness, and physical function. The third outcome measure was mean change in Lequence score. HA and GS were effective in reducing WOMAC pain by 20 % (differences of 43.5 % and 25.4 %) and 50 % (differences of 43.4 % and 26.9 %). Both HA and GS significantly reduced WOMAC pain, WOMAC stiffness, and WOMAC normalized score compared with placebo group (all P < 0.05). IAHA was significantly more effective than oral GS in improving WOMAC normalized score (P = 0.034), pain (P = 0.002), stiffness (P = 0.018), and function (P = 0.044). The results indicate that HA and GS were more effective than placebo in treating KBD and HA was more effective than GS.

  19. Effect of hyaluronic acid and polysaccharides from Opuntia ficus indica (L.) cladodes on the metabolism of human chondrocyte cultures.

    PubMed

    Panico, A M; Cardile, V; Garufi, F; Puglia, C; Bonina, F; Ronsisvalle, S

    2007-05-04

    Conventional medications in articular disease are often effective for symptom relief, but they can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective as non-steroidal anti-inflammatory drugs at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favourable influence on the course of the disease. In this study, we assay the anti-inflammatory/chondroprotective effect of some lyophilised extracts obtained from Opuntia ficus indica (L.) cladodes and of hyaluronic acid (HA) on the production of key molecules released during chronic inflammatory events such as nitric oxide (NO), glycosaminoglycans (GAGs), prostaglandins (PGE(2)) and reactive oxygen species (ROS) in human chondrocyte culture, stimulated with proinflammatory cytokine interleukin-1 beta (IL-1 beta). Further the antioxidant effect of these extracts was evaluated in vitro employing the bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test). All the extracts tested in this study showed an interesting profile in active compounds. Particularly some of these extracts were characterized by polyphenolic and polysaccharidic species. In vitro results pointed out that the extracts of Opuntia ficus indica cladodes were able to contrast the harmful effects of IL-1 beta. Our data showed the protective effect of the extracts of Opuntia ficus indica cladodes in cartilage alteration, which appears greater than that elicited by hyaluronic acid (HA) commonly employed as visco-supplementation in the treatment of joint diseases.

  20. Production of a composite hyaluronic acid/gelatin blood plasma gel for hydrogel-based adipose tissue engineering applications.

    PubMed

    Korurer, Esra; Kenar, Halime; Doger, Emek; Karaoz, Erdal

    2014-07-01

    Standard approaches to soft-tissue reconstruction include autologous adipose tissue transplantation, but most of the transferred adipose tissue is generally reabsorbed in a short time. To overcome this problem, long lasting implantable hydrogel materials that can support tissue regeneration must be produced. The purpose of this study was to evaluate the suitability of composite 3D natural origin scaffolds for reconstructive surgery applications through in vitro tests. The Young's modulus of the glutaraldehyde crosslinked hyaluronic acid/gelatin (HA/G) plasma gels, composed of human platelet-poor plasma, gelatin and human umbilical cord hyaluronic acid, was determined as 3.5 kPa, close to that of soft tissues. The composite HA/G plasma gels had higher porosity than plain plasma gels (72.5% vs. 63.86%). Human adipose tissue derived stem cells (AD-MSCs) were isolated from human lipoaspirates and characterized with flow cytometry, and osteogenic and adipogenic differentiation. Cell proliferation assay of AD-MSCs on the HA/G plasma gels revealed the nontoxic nature of these constructs. Adipogenic differentiation was distinctly better on HA/G plasma gels than on plain plasma gels. The results showed that the HA/G plasma gel with its suitable pore size, mechanical properties and excellent cell growth and adipogenesis supporting properties can serve as a useful scaffold for adipose tissue engineering applications.

  1. Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels

    PubMed Central

    Wu, Yijun; Yao, Jing; Zhou, Jianping; Dahmani, Fatima Zohra

    2013-01-01

    For nearly a decade, thermoresponsive ophthalmic in situ gels have been recognized as an interesting and promising ocular topical delivery vehicle for lipophilic drugs. In this study, a series of thermosensitive copolymers, hyaluronic acid-g-poly(N-isopropylacrylamide) (HA-g-PNIPAAm), was synthesized, by coupling carboxylic end-capped PNIPAAm to aminated hyaluronic acid through amide bond linkages, and was used as a potential carrier for the topical ocular administration of cyclosporine A (CyA). The lower critical solution temperature of HA-g-PNIPAAm59 in aqueous solutions was measured as 32.7°C, which was not significantly affected by the polymer concentration. Moreover, HA-g-PNIPAAm59 microgels showed a high drug loading efficiency (73.92%) and a controlled release profile that are necessary for biomedical application. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) observations showed that HA-g-PNIPAAm microgels were spherical in shape with homogeneous size. Based on the result of the eye irritation test, the HA-g-PNIPAAm microgels formulation was shown to be safe and nonirritant for rabbit eyes. In addition, HA-g-PNIPAAm microgels achieved significantly higher CyA concentration levels in rabbit corneas (1455.8 ng/g of tissue) than both castor oil formulation and commercial CyA eye drops. Therefore, these newly described thermoresponsive HA-g-PNIPAAm microgels demonstrated attractive properties to serve as pharmaceutical delivery vehicles for a variety of ophthalmic applications. PMID:24092975

  2. Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells

    PubMed Central

    Lee, Jong Heon; Lee, Jong Soo; Kim, Sujin

    2017-01-01

    This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion. PMID:28280412

  3. Viscosupplementation with intra-articular hyaluronic acid for hip disorders. A systematic review and meta-analysis

    PubMed Central

    Piccirilli, Eleonora; Oliva, Francesco; Murè, Mihaela Aconstantinesei; Mahmoud, Asmaa; Foti, Calogero; Tarantino, Umberto; Maffulli, Nicola

    2016-01-01

    Summary Background Hip joint diseases are common in adult population and their prevalence increases with age. Osteoarthritis, rheumatoid arthritis and femoroacetabular impingement are the most common chronic diseases in the hip joint. Viscosupplementation with exogenous hyaluronic acid (HA) is one of the most widely used conservative treatment aiming to improve synovial fluid properties and to decrease pain. There is no global consensus on the type of HA, method of injection and frequency, or on its efficacy in hip joint. Methods We selected published data in English in the PubMed and Google Scholar electronic databases up to March 2016 about hyaluronic acid injections in hip disorders. Results 26 articles were included following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Conclusion There is a lack of standardization of HA injections for hip conditions. Our results suggest that this is the best conservative therapy before surgery and it can act on pain relief and function however there is no evidence to prove its ability to modify the morphological structure of the pathological hip and the natural history of the disease. There are few data about the use of HA in other hip disorders rather than osteoarthritis. The most relevant evidence seems to show the utility of HA injections in improving synovial inflammation, but only a few studies have been conducted. Level of evidence I. PMID:28066733

  4. Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin.

    PubMed

    Pradhan, Roshan; Ramasamy, Thiruganesh; Choi, Ju Yeon; Kim, Jeong Hwan; Poudel, Bijay Kumar; Tak, Jin Wook; Nukolova, Natalia; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-06-05

    Multiple-drug combination therapy is becoming more common in the treatment of advanced cancers because this approach can decrease side effects and delay or prevent drug resistance. In the present study, we developed hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA NPs) for co-delivery of docetaxel (DTX) and tanespimycin (17-AAG). DTX and 17-AAG were simultaneously loaded into HA-PLGA NPs using an oil-in-water emulsification/solvent evaporation method. Several formulations were tested. HA-PLGA NPs loaded with DTX and 17-AAG at a molar ratio of 2:1 produced the smallest particle size (173.3±2.2nm), polydispersity index (0.151±0.026), and zeta potential (-12.4±0.4mV). Approximately 60% and 40% of DTX and 17-AAG, respectively, were released over 168h in vitro. Cytotoxicity assays performed in vitro using MCF-7, MDA-MB-231, and SCC-7 cells showed that dual drug-loaded HA-PLGA NPs at a DTX:17-AAG molar ratio of 2:1 exhibited the highest synergistic effect, with combination index values of 0.051, 0.036, and 0.032, respectively, at the median effective dose. Furthermore, synergistic antitumor activity was demonstrated in vivo in a CD44 and RHAMM (CD168) - overexpressing squamous cell carcinoma (SCC-7) xenograft in nude mice. These findings indicated that nanosystem-based co-delivery of DTX and 17-AAG could provide a promising combined therapeutic strategy for enhanced antitumor therapy.

  5. Generation of Vascular Graft Biomaterials via the Modification of Polyurethane with Hyaluronic Acid

    NASA Astrophysics Data System (ADS)

    Ruiz, Amaliris

    Cardiovascular disease is the leading cause of mortality in the United States, necessitating surgical interventions such as small diameter (I.D. <6 mm) bypass grafting. Although the use of autologous veins as small diameter grafts produces favorable results, their limited availability provides a significant obstacle. Meanwhile, several synthetic materials have demonstrated success as large-diameter vascular grafts, but exhibit poor patency and high failure rates in small-diameter applications. Based on these limitations and the clinical issues associated with them, it is clear that there is a significant need to develop new materials for cardiovascular and blood-contacting applications that could be used to fabricate small-diameter vascular grafts. Thus, in this thesis we have designed and characterized a new polymer that is composed of both synthetic and natural elements with the goal of generating a material that is appropriate for use in cardiovascular applications. Specifically, we describe the modification of polyurethane (PU), a synthetic polymer with many favorable physical characteristics, with hyaluronic acid (HA), a native glycosaminoglycan that possesses anti-thrombotic properties as well as the ability to modulate endothelial cell proliferation in a molecular weight-dependent manner. The goal of the present work was to assess in detail the impact of 1) HA molecular weight, 2) HA quantity, and 3) the method of HA incorporation (bulk vs. surface-grafted) on the vascular-specific performance of polyurethane-HA (PU-HA) materials, under static conditions and upon exposure to physiological shear stresses. The initial findings presented in this thesis indicate that these PU-HA materials possess many of the physical and biological properties that are necessary for implementation in vascular applications. These materials were able to simultaneously address the three major design criteria in vascular graft fabrication: hemocompatibility, endothelialization, and

  6. Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens

    PubMed Central

    Ochyl, Lukasz J.; Akerberg, Jonathan; Moon, James J.

    2015-01-01

    Here we report the development of a new cationic liposome-hyaluronic acid (HA) hybrid nanoparticle (NP) system and present our characterization of these NPs as an intranasal vaccine platform using a model antigen and F1-V, a candidate recombinant antigen for Yersinia pestis, the causative agent of plague. Incubation of cationic liposomes composed of DOTAP and DOPE with anionic HA biopolymer led to efficient ionic complexation and formation of homogenous liposome-polymer hybrid NPs, as evidenced by fluorescence resonance energy transfer, dynamic light scattering, and nanoparticle tracking analyses. Incorporation of cationic liposomes with thiolated HA allowed for facile surface decoration of NPs with thiol-PEG, resulting in the formation of DOTAP/HA core-PEG shell nanostructures. These NPs, termed DOTAP-HA NPs, exhibited improved colloidal stability and prolonged antigen release. In addition, cytotoxicity associated with DOTAP liposomes (LC50 ~0.2 mg/ml) was significantly reduced by at least 20-fold with DOTAP-HA NPs (LC50 > 4 mg/ml), as measured with bone marrow dendritic cells (BMDCs). Furthermore, NPs co-loaded with ovalbumin (OVA) and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA-specific CD8+ T cell and antibody responses. Importantly, intranasal vaccination with NPs co-loaded with F1-V and MPLA induced potent humoral immune responses with 11-, 23-, and 15-fold increases in F1-V-specific total IgG, IgG1, and IgG2c titers in immune sera by day 77, respectively, and induced balanced Th1/Th2 humoral immune responses, compared with the lack of sero-conversion in mice immunized with the equivalent doses of soluble F1-V vaccine. Overall, these results suggest that liposome-polymer hybrid NPs may serve as a promising vaccine delivery platform for intranasal vaccination against Y

  7. Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens.

    PubMed

    Fan, Yuchen; Sahdev, Preety; Ochyl, Lukasz J; J Akerberg, Jonathan; Moon, James J

    2015-06-28

    Here we report the development of a new cationic liposome-hyaluronic acid (HA) hybrid nanoparticle (NP) system and present our characterization of these NPs as an intranasal vaccine platform using a model antigen and F1-V, a candidate recombinant antigen for Yersinia pestis, the causative agent of plague. Incubation of cationic liposomes composed of DOTAP and DOPE with anionic HA biopolymer led to efficient ionic complexation and formation of homogenous liposome-polymer hybrid NPs, as evidenced by fluorescence resonance energy transfer, dynamic light scattering, and nanoparticle tracking analyses. Incorporation of cationic liposomes with thiolated HA allowed for facile surface decoration of NPs with thiol-PEG, resulting in the formation of DOTAP/HA core-PEG shell nanostructures. These NPs, termed DOTAP-HA NPs, exhibited improved colloidal stability and prolonged antigen release. In addition, cytotoxicity associated with DOTAP liposomes (LC50~0.2mg/ml) was significantly reduced by at least 20-fold with DOTAP-HA NPs (LC50>4mg/ml), as measured with bone marrow derived dendritic cells (BMDCs). Furthermore, NPs co-loaded with ovalbumin (OVA) and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA-specific CD8(+) T cell and antibody responses. Importantly, intranasal vaccination with NPs co-loaded with F1-V and MPLA induced potent humoral immune responses with 11-, 23-, and 15-fold increases in F1-V-specific total IgG, IgG1, and IgG2c titers in immune sera by day 77, respectively, and induced balanced Th1/Th2 humoral immune responses, whereas mice immunized with the equivalent doses of soluble F1-V vaccine failed to achieve sero-conversion. Overall, these results suggest that liposome-polymer hybrid NPs may serve as a promising vaccine delivery platform for intranasal vaccination against Y

  8. Dynamic interfacial behavior of viscoelastic aqueous hyaluronic acid: effects of molecular weight, concentration and interfacial velocity.

    PubMed

    Vorvolakos, Katherine; Coburn, James C; Saylor, David M

    2014-04-07

    An aqueous hyaluronic acid (HA(aq)) pericellular coat, when mediating the tactile aspect of cellular contact inhibition, has three tasks: interface formation, mechanical signal transmission and interface separation. To quantify the interfacial adhesive behavior of HA(aq), we induce simultaneous interface formation and separation between HA(aq) and a model hydrophobic, hysteretic Si-SAM surface. While surface tension γ remains essentially constant, interface formation and separation depend greatly on concentration (5 ≤ C ≤ 30 mg mL(-1)), molecular weight (6 ≤ MW ≤ 2000 kDa) and interfacial velocity (0 ≤ V ≤ 3 mm s(-1)), each of which affect shear elastic and loss moduli G′ and G′′, respectively. Viscoelasticity dictates the mode of interfacial motion: wetting-dewetting, capillary necking, or rolling. Wetting-dewetting is quantified using advancing and receding contact angles θ(A) and θ(R), and the hysteresis between them, yielding data landscapes for each C above the [MW, V] plane. The landscape sizes, shapes, and curvatures disclose the interplay, between surface tension and viscoelasticity, which governs interfacial dynamics. Gel point coordinates modulus G and angular frequency ω appear to predict wetting-dewetting (G < 75 ω0.2), capillary necking (75 ω0.2 < G < 200 ω0.075) or rolling (G > 200ω0.075). Dominantly dissipative HA(aq) sticks to itself and distorts irreversibly before separating, while dominantly elastic HA(aq) makes contact and separates with only minor, reversible distortion. We propose the dimensionless number (G′V)/(ω(r)γ), varying from 10(-5) to 10(3) in this work, as a tool to predict the mode of interface formation-separation by relating interfacial kinetics with bulk viscoelasticity. Cellular contact inhibition may be thus aided or compromised by physiological or interventional shifts in [C, MW, V], and thus in (G′V)/(ω(r)γ), which affect both mechanotransduction and interfacial dynamics. These observations

  9. Serum hyaluronic acid predicts protein-energy malnutrition in chronic hepatitis C

    PubMed Central

    Nishikawa, Hiroki; Enomoto, Hirayuki; Yoh, Kazunori; Iwata, Yoshinori; Hasegawa, Kunihiro; Nakano, Chikage; Takata, Ryo; Kishino, Kyohei; Shimono, Yoshihiro; Sakai, Yoshiyuki; Nishimura, Takashi; Aizawa, Nobuhiro; Ikeda, Naoto; Takashima, Tomoyuki; Ishii, Akio; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Abstract Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient <0.85 using indirect calorimetry as having PEM. We investigated the effect of serum HA level on the presence of PEM. Receiver operating characteristic curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for serum HA level, platelet count, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, and Forns index for the presence of PEM. The median serum HA level in this study was 148.0 ng/mL (range: 9.0–6340.0 ng/mL). In terms of the degree of liver function (chronic hepatitis, Child-Pugh A, B, and C), the analyzed patients were well stratified according to serum HA level (overall significance, P < 0.0001). The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6–6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0–783.0 ng/mL) (P < 0.0001). Among 6 fibrosis markers, serum HA level yielded the highest AUROC with a level of 0.849 at an optimal cut-off value of 151.0 ng/mL (sensitivity 93.4%; specificity 62.0%; P < 0.0001). In the multivariate analysis, serum HA level was found to be a significant prognostic factor related to the presence of PEM (P = 0.0001). In conclusion, serum HA level can be a useful predictor of PEM in patients with CHC. PMID:27311000

  10. Hyaluronic acid abrogates ethanol-dependent inhibition of collagen biosynthesis in cultured human fibroblasts

    PubMed Central

    Donejko, Magdalena; Przylipiak, Andrzej; Rysiak, Edyta; Miltyk, Wojciech; Galicka, Elżbieta; Przylipiak, Jerzy; Zaręba, Ilona; Surazynski, Arkadiusz

    2015-01-01

    Introduction The aim of the study was to evaluate the effect of ethanol on collagen biosynthesis in cultured human skin fibroblasts, and the role of hyaluronic acid (HA) in this process. Regarding the mechanism of ethanol action on human skin fibroblasts we investigated: expression of β1 integrin and insulin-like growth factor 1 receptor (IGF-IR), signaling pathway protein expression: mitogen-activated protein kinases (MAPKs), protein kinase B (Akt), nuclear factor kappa B (NF-κB) transcription factor, cytotoxicity assay and apoptosis, metalloproteinase activity, as well as the influence of HA on these processes. Materials and methods Collagen biosynthesis, activity of prolidase, DNA biosynthesis, and cytotoxicity were measured in confluent human skin fibroblast cultures that have been treated with 25, 50, and 100 mM ethanol and with ethanol and 500 µg/mL HA. Western blot analysis and zymography were performed to evaluate expression of collagen type I, β1 integrin receptor, IGF-IR, NF-κB protein, phospho-Akt protein, kinase MAPK, caspase 9 activity, and matrix metalloproteinases (MMP-9 and MMP-2). Results Ethanol in a dose-dependent manner lead to the impairment of collagen biosynthesis in fibroblast cultures through decreasing prolidase activity and expression of β1 integrin and IGF-IR. This was accompanied by an increased cytotoxicity, apoptosis and lowered expression of the signaling pathway proteins induced by β1 integrin and IGF-IR, that is, MAPK (ERK1/2) kinases. The lowered amount of synthesized collagen and prolidase activity disturbance may also be due to the activation of NF-κB transcription factor, which inhibits collagen gene expression. It suggests that the decrease in fibroblast collagen production may be caused by the disturbance in its biosynthesis but not degradation. The application of HA has a protective effect on disturbances caused by the examined substances. It seems that regulatory mechanism of ethanol-induced collagen aberration take

  11. Hyaluronic acid based hydrogel system for soft tissue regeneration and drug delivery

    NASA Astrophysics Data System (ADS)

    Jha, Amit Kumar

    We have developed hyaluronic acid (HA)-based, biomimetic hydrogel matrices that are hierarchically structured, mechanically robust and biologically active. Specifically, HA-based hydrogel particles (HGPs) with controlled sizes, defined porosity, and improved stability were synthesized using different inverse emulsion systems and crosslinking chemistries. The resultant particles either contained residual functional groups or were rendered reactive by subsequent chemical modifications. HA-based doubly crosslinked networks (DXNs) were synthesized via covalent crosslinking of HA HGPs with soluble HA macromers carrying mutually reactive functional groups. These hybrid matrices are hierarchical in nature, consisting of densely crosslinked HGPs integrated in a loosely connected secondary matrix. Their mechanical properties and degradation kinetics can be readily tuned by varying the particle size, functional group density, intra- and interparticle crosslinking. To improve the biological functions of HA HGPs, perlecan domain I (PlnDI), a basement membrane proteoglycan that has strong affinity for various heparin binding growth factors (HBGFs), was successfully conjugated to the particles through the core protein via a flexible poly(ethylene glycol) (PEG) linker. The immobilized PlnDI maintains its ability to bind bone morphogenetic proteins (BMP-2) and modulates its in vitro release. A similar, sustained release of BMP-2 was achieved by encapsulating BMP-2-loaded HGPs within a photocrosslinked HA matrix. When encapsulated in HA DXNs, primary bovine chondrocytes were able to maintain their phenotype, proliferate readily and produce abundant glycosaminoglycan. Finally, cell-adhesive HA DXNs were fabricated by encapsulating gelatin-decorated HA HGPs in a secondary HA matrix. Human MSCs were shown to adhere to the composite matrix through the focal adhesion sites clustered on particle surface. The cell-adhesive composite matrices supported hMSC proliferation and migration into

  12. Combined application of acellular bovine pericardium and hyaluronic acid in prevention of postoperative pericardial adhesion.

    PubMed

    Shen, Jia; Xu, Zhi Wei

    2014-03-01

    An experiment was designed to find the suitable acellular bovine pericardium (ABP) patch in pericardial cavity reconstruction and to evaluate the effect of sodium hyaluronic acid (NaHA) on inflammatory reaction in prevention of pericardial adhesions. The pericardial adhesion model was established in 20 rabbits, weighing from 3.2 to 3.6 kg. Groups were classified as follows: Group A (n = 5), the control group, the pericardium was directly closed; Group B (n = 5), 0.15% glutaraldehyde-treated ABP (low cross-link degree); Group C, 0.3% glutaraldehyde-treated ABP (middle cross-link degree); Group D, 0.15% glutaraldehyde-treated ABP + NaHA solution. Blood samples were collected at 6 h, 24 h, 3 days, and 5 days, to assay postoperative inflammatory reaction. The tenacity and severity of adhesions were evaluated 2 months after operation, by macroscopic and microscopic examinations, and Q-PCR (real-time quantitative polymerase chain reaction) test was used to quantitatively analyze the associated genes with adhesion. Pericardium regeneration was demonstrated by immunohistochemical technique to identify mesothelial cells. In Group D, the serum concentration of tumor necrosis factor-α (TNF-α) was significantly lower in the early postoperative period, and the mean adhesion score (adhesion between the epicardium and ABP) was significantly lower compared with the control group (Groups D vs. A: 0.20 ± 0.45 vs. 2.00 ± 0.71, P = 0.009*). The signs of degradation of the ABPs were observed 2 months postoperation in Groups D and B. Immunohistochemically, the positive cytokeratin AE1 staining results demonstrated the relatively total regeneration of the pericardium in Group D. Signs of regeneration were observed in Group D. Compared with the control group, the level of TGF-β2 in Group D was significantly lower (0.00132 ± 0.00114, P = 0.022*). The TGF-β3 level was statistically significant, being highest in Group D (0.00805 ± 0.00136, P = 0.029*). The mean quantity of Smad6 in

  13. Inhibition of Hyaluronic Acid Synthesis Suppresses Angiogenesis in Developing Endometriotic Lesions

    PubMed Central

    Olivares, Carla N.; Alaniz, Laura D.; Menger, Michael D.; Barañao, Rosa I.; Laschke, Matthias W.; Meresman, Gabriela F.

    2016-01-01

    Background The development and long-term survival of endometriotic lesions is crucially dependent on an adequate vascularization. Hyaluronic acid (HA) through its receptor CD44 has been described to be involved in the process of angiogenesis. Objective To study the effect of HA synthesis inhibition using non-toxic doses of 4-methylumbelliferone (4-MU) on endometriosis-related angiogenesis. Materials and Methods The cytotoxicity of different in vitro doses of 4-MU on endothelial cells was firstly tested by means of a lactate dehydrogenase assay. The anti-angiogenic action of non-cytotoxic doses of 4-MU was then assessed by a rat aortic ring assay. In addition, endometriotic lesions were induced in dorsal skinfold chambers of female BALB/c mice, which were daily treated with an intraperitoneal injection of 0.9% NaCl (vehicle group; n = 6), 20mg/kg 4-MU (n = 8) or 80mg/kg 4-MU (n = 7) throughout an observation period of 14 days. The effect of 4-MU on their vascularization, survival and growth were studied by intravital fluorescence microscopy, histology and immunohistochemistry. Main Results Non-cytotoxic doses of 4-MU effectively inhibited vascular sprout formation in the rat aortic ring assay. Endometriotic lesions in dorsal skinfold chambers of 4-MU-treated mice dose-dependently exhibited a significantly smaller vascularized area and lower functional microvessel density when compared to vehicle-treated controls. Histological analyses revealed a downregulation of HA expression in 4-MU-treated lesions. This was associated with a reduced density of CD31-positive microvessels within the lesions. In contrast, numbers of PCNA-positive proliferating and cleaved caspase-3-positive apoptotic cells did not differ between 4-MU-treated and control lesions. Conclusions The present study demonstrates for the first time that targeting the synthesis of HA suppresses angiogenesis in developing endometriotic lesions. Further studies have to clarify now whether in the future this

  14. Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

    NASA Astrophysics Data System (ADS)

    Erickson, Isaac E.

    2011-12-01

    Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 k

  15. Hyaluronic acid reverses the abnormal synthetic activity of human osteoarthritic subchondral bone osteoblasts.

    PubMed

    Lajeunesse, Daniel; Delalandre, Aline; Martel-Pelletier, Johanne; Pelletier, Jean Pierre

    2003-10-01

    The underlying mechanisms responsible for both cartilage loss and subchondral bone changes in osteoarthritis (OA) remain unknown. It is becoming recognized that the extracellular matrix influences the metabolism of cells both in vivo and in vitro and can modify their responses to external stimuli. Indeed, the glycosaminoglycan/proteoglycan matrix is of major importance for the proliferation and/or differentiation of a number of cells. Here, we determined the potential role of hyaluronic acid (HA) of increasing molecular weight (MW) to alter the expression of metabolic markers and cytokine production by human osteoarthritic (OA) subchondral osteoblasts (Ob). Both 1,25(OH)(2)D(3)-induced alkaline phosphatase activity (ALPase) and osteocalcin release were increased in OA Ob when compared to normal. HA reduced osteocalcin release in OA Ob at MW of 300 and above, whereas HA failed to significantly modify ALPase. Parathyroid hormone (PTH) stimulated cyclic AMP (cAMP) formation by OA Ob. HA had a biphasic effect on this PTH-dependent activity, totally inhibiting cAMP formation at MW of 300 and 800. HA of increasing MW progressively reduced the levels of Prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6) produced by OA Ob. Interestingly, urokinase plasminogen activator (uPA) and and PA inhibitor-1 (PAI-1) levels were not significantly affected by HA of increasing MW; however, the PAI-1 to uPA ratio showed a slight, yet nonsignificant increase. Surprisingly, uPA activity was increased in OA Ob under the same conditions. Last, HA had no effect on the production of insulin-like growth factor-1 by these cells. Our data suggest that high MW HA can modify cellular parameters in OA Ob that are increased when compared to normal. The effect of HA on inflammatory mediators, such as PGE(2) and IL-6, and on uPA activity is more striking at higher MW as well. Taken together, these results could suggest that HA of increasing MW has positive effects on OA Ob by modifying their

  16. The composition and physicochemical properties of hyaluronic acids prepared from ox synovial fluid and from a case of mesothelioma

    PubMed Central

    Preston, B. N.; Davies, M.; Ogston, A. G.

    1965-01-01

    1. Materials containing hyaluronic acid have been prepared by filtration (Ogston & Stanier, 1950) from ox synovial fluid and from a protein-rich human mesothelioma fluid. The ox material has been deproteinized by treatment with chloroform and pentanol and by gradient elution on DEAE-Sephadex; several fractions were obtained by the latter method. These materials can be stored in solution at −20° without change of properties. The ox material contained 21% of protein; all other preparations contained less than 6% of protein. 2. The two materials have been compared by sedimentation and viscosity and shown to be closely similar. Treatment of the ox material with neuraminidase caused no change in its viscosity behaviour. 3. Information about the molecular configuration of the ox material has been obtained from measurements of light-scattering and viscosity. The results, though consistent with a highly extended configuration, are not consistent with a linear random-coil configuration. It is tentatively suggested that the structure may have some degree of branching and of cross-linking, which give it a rigidity with respect to expansion of the molecular domain that would not be possessed by a random coil. 4. The deproteinized material recovered from DEAE-Sephadex, though polydisperse, showed unchanged average molecular weight; however, the average radius of gyration was greater than before this treatment. 5. Acidification to approx. pH3 resulted in a contraction of the structure, with only a slight degree of expansion when the pH was restored to 6·8–7·0. 6. Measurements of optical rotatory dispersion qualitatively support a structure less simple than a linear random coil. 7. Colloid osmotic pressures of mixed solutions of bovine serum albumin and of hyaluronic acid prepared by filtration from ox synovial fluid have been measured. The results agree approximately with those of Laurent & Ogston (1963) but are in quantitative disagreement with the partition measurements

  17. Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.

    PubMed

    Han, Xiaofeng; Wang, Zhe; Wang, Manyuan; Li, Jing; Xu, Yongsong; He, Rui; Guan, Hongyu; Yue, Zhujun; Gong, Muxin

    2016-06-01

    In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and Cmax level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics.

  18. [Evaluation of the use of hyaluronic acid in iatrogenic scars after phonosurgery (excluding surgical oncology) and ligamento-epithelial abnormalities of the vocal cords].

    PubMed

    Perouse, R; Coulombeau, B

    2013-01-01

    Between January of 2007 and December of 2011, six patients underwent revision microphonosurgery because of scarring complicating the initial surgery. The technique consisted of detaching the scarred area, the insertion of fibrils of hyaluronic acid (Merogel), a microsuture and possibly intra-cordal fat injection. A pre-and post-operative phoniatric protocol assessed the results which appear encouraging.

  19. Topical Hyaluronic Acid vs. Standard of Care for the Prevention of Radiation Dermatitis After Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    SciTech Connect

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

    2012-07-15

    Purpose: To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of {>=}Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Methods and Materials: Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of {>=}Grade 2 dermatitis. Results: The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of {>=}Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only 1ne patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). Conclusion: We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of {>=}Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop.

  20. [Hyaluronic acid, receptor CD44, and their role in diabetic complications].

    PubMed

    Ievdokimova, N Iu

    2008-01-01

    Hyaluronic acid (HA) is a straight chain glycosaminoglycan polymer composed of repeating units of the disaccharide [-D-glucuronic acid-beta1,3-N-acetyl-D-glucosamine-beta1,4-]n, and is found in vertebrates and certain microorganisms. The molecular weight of HA chains is usually equal to approximately 1-10 and MDa, n > 10(3-4), although it can exists as oligosaccharides under some physiological and pathological conditions. HA resides on the cell surface or in the extracellular space, but it also occurred inside the mammalian cells. HA is synthesized in mammals by three enzymes with polymers of varying chain length. The biological functions of HA include the maintenance of elastoviscosity of liquid connective tissues, control of tissue hydration, supramolecular assembly of proteoglycans in the extracellular matrix and besides numerous receptor-mediated functions in cell attachment, mitosis, migration, tumor development, wound healing and inflammation. The extensive repertoire of biological functions of HA corresponds to the existence of a large repertoire of HA-binding proteins (hyaladherins). Many hyaladherins contain a common structural domain, termed a Link module, which is involved in ligand binding. The most important member of the Link module superfamily is the main HA receptor, CD44. CD44 has diverse functions including not only the organization and metabolism of extracellular matrix, but also engage the cytoskeleton and co-ordinate signaling events to enable the cell responce to changes in the environment. HA has an extraordinary high rate of turnover, and at the cellular level it is considered to be degraded progressively by a series of enzymatic reactions that generate polymers of decreasing sizes. HA biological effects are known to be determined by the polymer size and depend on the cell type. For example, the native high molecular weight HA is anti-angiogenic, while its degradation products (6-20 saccharides) stimulate endothelial cell proliferation

  1. Efficacy and Safety of a Low Molecular Weight Hyaluronic Acid Topical Gel in the Treatment of Facial Seborrheic Dermatitis Final Report

    PubMed Central

    Rowland Powell, Callie

    2014-01-01

    Objective: Hyaluronic acid sodium salt gel 0.2% is a topical device effective in reducing skin inflammation. Facial seborrheic dermatitis, characterized by erythema and or flaking/scaling in areas of high sebaceous activity, affects up to five percent of the United States population. Despite ongoing study, the cause of the condition is yet unknown, but has been associated with yeast colonization and resultant immune derived inflammation. First-line management typically is with keratolytics, topical steroids, and topical antifungals as well as the targeted immunosuppressant agents pimecrolimus and tacrolimus. The objective of this study was to evaluate the efficacy and safety of a novel topical antiinflammatory containing low molecular weight hyaluronic acid. Design and setting: Prospective, observational, non-blinded safety and efficacy study in an outpatient setting. Participants: Individuals 18 to 75 years of age with facial seborrheic dermatitis. Measurements: Outcome measures included scale, erythema, pruritus, and the provider global assessment, all measured on a five-point scale. Subjects were assessed at baseline, Week 2, Week 4, and Week 8. Results: Final data with 13 of 17 subjects are presented. Hyaluronic acid sodium salt gel 0.2% was shown through visual grading assessments to improve the provider global assessment by 65.48 percent from baseline to Week 4. Reductions in scale, erythema, and pruritus were 76.9, 64.3, and 50 percent, respectively, at Week 4. At Week 8, the provider global assessment was improved from baseline in 92.3 percent of subjects. Conclusion: Treatment with topical low molecular weight hyaluronic acid resulted in improvement in the measured endpoints. Final data reveal continued improvement from that seen in the interim data shown previously. Topical low molecular weight hyaluronic acid is another option that may be considered for the treatment of facial seborrheic dermatitis in the adult population. Compliance and tolerance were

  2. The effectiveness of injections of hyaluronic acid or corticosteroid in patients with subacromial impingement: a three-arm randomised controlled trial.

    PubMed

    Penning, L I F; de Bie, R A; Walenkamp, G H I M

    2012-09-01

    A total of 159 patients (84 women and 75 men, mean age of 53 (20 to 87)) with subacromial impingement were randomised to treatment with subacromial injections using lidocaine with one of hyaluronic acid (51 patients), corticosteroid (53 patients) or placebo (55 patients). Patients were followed up for 26 weeks. The primary outcome was pain on a visual analogue score (VAS), and secondary outcomes included the Constant Murley score, shoulder pain score, functional mobility score, shoulder disability questionnaire and pain-specific disability score. The different outcome measures showed similar results. After three, six and 12 weeks corticosteroid injections were superior to hyaluronic acid injections and only at six weeks significantly better than placebo injections. The mean short-term reduction in pain on the VAS score at 12 weeks was 7% (SD 2.7; 97.5% confidence interval (CI) 0.207 to 1.55; p = 0.084) in the hyaluronic acid group, 28% (SD 2.8; 97.5% CI 1.86 to 3.65; p < 0.001) in the corticosteroid group and 23% (SD 3.23; 97.5% CI 1.25 to 3.26; p < 0.001) in the placebo group. At 26 weeks there was a reduction in pain in 63% (32 of 51) of patients in the hyaluronic acid group, 72% (38 of 53) of those in the corticosteroid group and 69% (38 of 55) of those in the placebo group. We were not able to show a convincing benefit from hyaluronic acid injections compared with corticosteroid or placebo injections. Corticosteroid injections produced a significant reduction in pain in the short term (three to 12 weeks), but in the long term the placebo injection produced the best results.

  3. Hyaluronic Acid Binding Sperm Selection for assisted reproduction treatment (HABSelect): study protocol for a multicentre randomised controlled trial

    PubMed Central

    Witt, K D; Beresford, L; Bhattacharya, S; Brian, K; Coomarasamy, A; Hooper, R; Kirkman-Brown, J; Khalaf, Y; Lewis, S E; Pacey, A; Pavitt, S; West, R

    2016-01-01

    Introduction The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial is to determine the efficacy of hyaluronic acid (HA)-selection of sperm versus conventionally selected sperm prior to ICSI on live birth rate (LBR). The mechanistic aim is to assess whether and how the chromatin state of HA-selected sperm corresponds with clinical outcomes—clinical pregnancy rate (CPR), LBR and pregnancy loss (PL). Methods and analysis Couples attending UK Centres will be approached, eligibility screening performed and informed consent sought. Randomisation will occur within 24 hours prior to ICSI treatment. Participants will be randomly allocated 1:1 to the intervention arm (physiological intracytoplasmic sperm injection, PICSI) versus the control arm using conventional methods (ICSI). The primary clinical outcome is LBR ≥37 weeks' gestation with the mechanistic study determining LBR's relationship with sperm DNA integrity. Secondary outcomes will determine this for CPR and PL. Only embryologists performing the procedure will be aware of the treatment allocation. Steps will be taken to militate against biases arising from embryologists being non-blinded. Randomisation will use a minimisation algorithm to balance for key prognostic variables. The trial is powered to detect a 5% difference (24–29%: p=0.05) in LBR ≥37 weeks' gestation. Selected residual sperm samples will be tested by one or more assays of DNA integrity. Ethics and dissemination HABSelect is a UK NIHR-EME funded study (reg no 11/14/34; IRAS REF. 13/YH/0162). The trial was designed in partnership with patient and public involvement to help maximise patient benefits. Trial findings will be

  4. Platelet Rich Plasma and Hyaluronic Acid Blend for the Treatment of Osteoarthritis: Rheological and Biological Evaluation

    PubMed Central

    Russo, Fabrizio; D’Este, Matteo; Vadalà, Gianluca; Cattani, Caterina; Papalia, Rocco; Alini, Mauro; Denaro, Vincenzo

    2016-01-01

    Introduction Osteoarthritis (OA) is the most common musculoskeletal disease. Current treatments for OA are mainly symptomatic and inadequate since none results in restoration of fully functional cartilage. Hyaluronic Acid (HA) intra-articular injections are widely accepted for the treatment of pain associated to OA. The goal of HA viscosupplementation is to reduce pain and improve viscoelasticity of synovial fluid. Platelet-rich plasma (PRP) has been also employed to treat OA to possibly induce cartilage regeneration. The combination of HA and PRP could supply many advantages for tissue repair. Indeed, it conjugates HA viscosupplementation with PRP regenerative properties. The aim of this study was to evaluate the rheological and biological properties of different HA compositions in combination with PRP in order to identify (i) the viscoelastic features of the HA-PRP blends, (ii) their biological effect on osteoarthritic chondrocytes and (iii) HA formulations suitable for use in combination with PRP. Materials and Methods HA/PRP blends have been obtained mixing human PRP and three different HA at different concentrations: 1) Sinovial, 0.8% (SN); 2) Sinovial Forte 1.6% (SF); 3) Sinovial HL 3.2% (HL); 4) Hyalubrix 1.5% (HX). Combinations of phosphate buffered saline (PBS) and the four HA types were used as control. Rheological measurements were performed on an Anton PaarMCR-302 rheometer. Amplitude sweep, frequency sweep and rotational measurements were performed and viscoelastic properties were evaluated. The rheological data were validated performing the tests in presence of Bovine Serum Albumin (BSA) up to ultra-physiological concentration (7%). Primary osteoarthritic chondrocytes were cultured in vitro with the HA and PRP blends in the culture medium for one week. Cell viability, proliferation and glycosaminoglycan (GAG) content were assessed. Results PRP addition to HA leads to a decrease of viscoelastic shear moduli and increase of the crossover point, due to a

  5. Construction of antibacterial poly(ethylene terephthalate) films via layer by layer assembly of chitosan and hyaluronic acid.

    PubMed

    Del Hoyo-Gallego, Sara; Pérez-Álvarez, Leyre; Gómez-Galván, Flor; Lizundia, Erlantz; Kuritka, Ivo; Sedlarik, Vladimir; Laza, Jose Manuel; Vila-Vilela, Jose Luis

    2016-06-05

    Polyelectrolytic multilayers (PEMs) with enhanced antibacterial properties were built up onto commercial poly(ethylene terephthalate) (PET) films based on the layer by layer assembling of bacterial contact killing chitosan and bacterial repelling highly hydrated hyaluronic acid. The optimization of the aminolysis modification reaction of PET was carried out by the study of the mechanical properties and the surface characterization of the modified polymers. The layer by layer assembly was successfully monitored by TEM microscopy, surface zeta-potential, contact angle measurements and, after labeling with fluorescein isothiocyanate (FTIC) by absorption spectroscopy and confocal fluorescent microscopy. Beside, the stability of the PEMs was studied at physiological conditions in absence and in the presence of lysozyme and hyaluronidase enzymes. Antibacterial properties of the obtained PEMs against Escherichia coli were compared with original commercial PET.

  6. Endoscopic Treatment of Vesicoureteral Reflux in Children with Dextranomer/Hyaluronic Acid-A Single Surgeon's 6-Year Experience.

    PubMed

    Chen, Hou-Chuan; Yeh, Chou-Ming; Chou, Chia-Man

    2010-01-01

    Endoscopic treatment for vesicoureteral reflux (VUR) has become an established alternative to long-term antibiotic prophylaxis and ureteral reimplantation. We present the outcome of endoscopic treatment with dextranomer/hyaluronic acid copolymer (Deflux) for VUR in children by a single surgeon at our institute from October 2003 to October 2009. We reviewed the cases of 150 patients (total 239 ureters), 56 girls (37%) and 94 boys (63%), with a mean age of 2.2 years and a median followup of 2.5 years (range 3-68 months). Among the 239 ureters treated, 67.4% (161/239) were cured with a single injection, and a second and third injection raised the cure rate to 86.6% (207/239) and 88.3% (211/239), respectively. None had postoperative ureteral obstruction.

  7. Cartilage oligomeric matrix protein and hyaluronic acid are sensitive serum biomarkers for early cartilage lesions in the knee joint.

    PubMed

    Jiao, Qiang; Wei, Lei; Chen, Chongwei; Li, Pengcui; Wang, Xiaohu; Li, Yongping; Guo, Li; Zhang, Congming; Wei, Xiaochun

    2016-01-01

    The purpose of this study was to evaluate the relationship between five previously established serum osteoarthritis biomarkers and the severity of cartilage lesions in the knee. Cartilage damage (classified according to the Outerbridge scoring system) and serum concentrations of cartilage oligomeric matrix protein (COMP), collagen type II C-telopeptide (CTX-II), matrix metalloproteinase-3 (MMP-3), collagen type III N-propeptide, (PIIINP), and hyaluronic acid (HA) were determined in 79 patients who underwent knee arthroscopy or total knee replacement. HA and COMP concentrations were significantly higher in the Outerbridge score 1 and 2 groups, respectively. These results suggest that serum COMP and HA concentrations can be used to predict early cartilage lesions in the knee.

  8. Preparation and characterization of a new gellan gum and sulphated hyaluronic acid hydrogel designed for epidural scar prevention.

    PubMed

    Cencetti, Claudia; Bellini, Davide; Longinotti, Cristina; Martinelli, Andrea; Matricardi, Pietro

    2011-02-01

    Postsurgical adhesions are a common problem in clinical practice, causing nerve compression, pain and discomfort. A new hydrogel based on gellan gum and sulphated hyaluronic acid was synthesized, with the aim to create an effective barrier for epidural scar formation. Physico-chemical properties of the gel were analyzed, and preliminary biocompatibility data (i.e. cytotoxicity) have been collected in view of its potential clinical use. The characterization of the new material demonstrated that the hydrogel, due to its high-viscosity, could effectively act as a barrier with a long in situ residence time. In addition, the hydrogel can be easily extruded from a syringe and its structure exhibits excellent stabilizing properties. Furthermore, biological assays showed that this gel is suitable for further preclinical development.

  9. Hyaluronic acid scaffold for skin defects in congenital syndactyly release surgery: a novel technique based on the regenerative model.

    PubMed

    Landi, A; Garagnani, L; Leti Acciaro, A; Lando, M; Ozben, H; Gagliano, M C

    2014-11-01

    Syndactyly release may require skin grafting to fill the skin defects, which might lead to complications or poor cosmetic outcomes. A simple graftless technique for syndactyly release with a hyaluronic acid (HA) scaffold used to cover the bare areas is described. Between 2008 and 2011, release of 26 webs in 23 patients was performed. All skin defects were covered with Hyalomatrix(®) PA. One patient was excluded due to early post-operative infection that required HA scaffold removal before its integration. Web creep, secondary deformities, scar quality, and patient and parental satisfaction were assessed. Mean follow-up of the group of 22 patients was 24 months. There were no secondary deformities and minimal degree of web creep. All patients had close to normal pigmentation and good pliability at the sites of scaffold application. The results confirm the use of a HA scaffold as a promising alternative to skin grafting in syndactyly release surgery.

  10. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    NASA Astrophysics Data System (ADS)

    Wei, Y. T.; Tian, W. M.; Yu, X.; Cui, F. Z.; Hou, S. P.; Xu, Q. Y.; Lee, In-Seop

    2007-09-01

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  11. Evaluation of an onion extract, Centella asiatica, and hyaluronic acid cream in the appearance of striae rubra.

    PubMed

    Draelos, Zoe Diana; Gold, Michael H; Kaur, Mandeep; Olayinka, Babajide; Grundy, Starr L; Pappert, Eric J; Hardas, Bhushan

    2010-01-01

    This study evaluated the effect of an onion extract cream with Centella asiatica and hyaluronic acid in improving the appearance of striae rubra (SR). Women participants with bilateral, outer aspect of the thigh SR were randomized to apply a quarter-sized amount of the onion extract cream twice daily for 12 weeks to the randomized left or right, outer aspect of the thigh. No treatment was administered to the contralateral side. Participants were evaluated at weeks 2, 4, 8, and 12. Primary efficacy endpoints included color, texture, softness, and overall appearance of SR by the participant and investigator at week 12. The treated thigh demonstrated a statistically significant difference in the mean change in participant and investigator evaluations in overall appearance, texture, color, and softness compared with the untreated thigh at week 12. No adverse events occurred during the study. The onion extract cream was well tolerated and significantly improved the appearance of SR in women.

  12. [USE OF HYALURONIC ACID ALONE AND COMBINED WITH ARGENTIC SULPHADIAZINE IN REACTIVE PERFORATING COLLAGENOSIS. A CASE REPORT].

    PubMed

    Cano Cerro, Miguel Mauricio; Jiménez Fornés, Eva María; Fabrich Lloret, María José; Gans Cuenca, Ovidio; Redón Martínez, Mara; Sales Molió, Elena

    2016-04-01

    The dermatosis known since reactive perforating collagenosis (RPC) is an injury that is characterized by the transepidermal elimination of the collagen. Two forms of presentation exist: the inherited one and the acquired one. The acquired form appears in the adult age, principally in diabetics with renal chronic insufficiency. The hyaluronic acid is a glycosaminoglycan of high place molecular weight that is synthesized in the system vacuolar of the fibroblasts and other cells, since they are the keratinocytes, with help of the factors of growth and in other cytokines. The argentic sulphadiazine is a hackneyed medicament of antiinfectious action that is in use for anticipating and treating the infections in wounds and burns of degree the II and IIIrd. His action realizes it on bacteria and fungi.

  13. Hyaluronic acid/chitosan multilayer coatings on neuronal implants for localized delivery of siRNA nanoplexes.

    PubMed

    Hartmann, Hanna; Hossfeld, Susanne; Schlosshauer, Burkhard; Mittnacht, Ursula; Pêgo, Ana Paula; Dauner, Martin; Doser, Michael; Stoll, Dieter; Krastev, Rumen

    2013-06-28

    Binding, stabilizing and promoting cellular uptake of siRNA are all critical efforts in creating matrices for the localized delivery of siRNA molecules to target cells. In this study, we describe the generation of chitosan imidazole/siRNA nanoplexes (NPs) embedded in nano scope polyelectrolyte multilayers (PEMs) composed of hyaluronic acid and chitosan for sustained and localized drug delivery. Regular PEM build-up, successful integration of NPs and controlled release under physiological conditions were shown. Biological efficacy was evaluated in neuronal cell culture concerning cell adhesion, viability, NPs uptake and gene silencing. The additionally shown biological functionalization of neuronal implants possesses potential for future applications in the field of regenerative medicine and treatment of spinal cord injuries.

  14. "Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption.

    PubMed

    Deng, Xudong; Korogiannaki, Myrto; Rastegari, Banafsheh; Zhang, Jianfeng; Chen, Mengsu; Fu, Qiang; Sheardown, Heather; Filipe, Carlos D M; Hoare, Todd

    2016-08-31

    Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification.

  15. Uptake of silica covered Quantum Dots into living cells: Long term vitality and morphology study on hyaluronic acid biomaterials.

    PubMed

    D'Amico, Michele; Fiorica, Calogero; Palumbo, Fabio Salvatore; Militello, Valeria; Leone, Maurizio; Dubertret, Benoit; Pitarresi, Giovanna; Giammona, Gaetano

    2016-10-01

    Quantum Dots (QDs) are promising very bright and stable fluorescent probes for optical studies in the biological field but water solubility and possible metal bio-contamination need to be addressed. In this work, a simple silica-QD hybrid system is prepared and the uptake in bovine chondrocytes living cells without any functionalization of the external protective silica shield is demonstrated. Moreover, long term treated cells vitality (up to 14days) and the transfer of silica-QDs to the next cell generations are here reported. Confocal fluorescence microscopy was also used to determine the morphology of the so labelled cells and the relative silica-QDs distribution. Finally, we employ silica-QD stained chondrocytes to characterize, as proof of concept, hydrogels obtained from an amphiphilic derivative of hyaluronic acid (HA-EDA-C18) functionalized with different amounts of the RGD peptide.

  16. Influence of Cross-Linkers on the in Vitro Chondrogenesis of Mesenchymal Stem Cells in Hyaluronic Acid Hydrogels.

    PubMed

    Maturavongsadit, Panita; Bi, Xiangdong; Metavarayuth, Kamolrat; Luckanagul, Jittima Amie; Wang, Qian

    2017-02-01

    This study aims to investigate the effect of the structures of cross-linkers on the in vitro chondrogenic differentiation of bone mesenchymal stem cells (BMSCs) in hyaluronic acid (HA)-based hydrogels. The hydrogels were prepared by the covalent cross-linking of methacrylated HA with different types of thiol-tailored molecules, including dithiothreitol (DTT), 4-arm poly(ethylene glycol) (PEG), and multiarm polyamidoamine (PAMAM) dendrimer using thiol-ene "click" chemistry. The microstructure, mechanical properties, diffusivity, and degradation rates of the resultant hydrogels were controlled by the structural feature of different cross-linkers. BMSCs were then encapsulated in the resulting hydrogels and cultured in chondrogenic conditions. Overall, chondrogenic differentiation was highly enhanced in the PEG-cross-linked HA hydrogels, as measured by glycosaminoglycan (GAG) and collagen accumulation. The physical properties of hydrogels, especially the mechanical property and microarchitecture, were resulted from the structures of different cross-linkers, which subsequently modulated the fate of BMSC differentiation.

  17. Growth factors-loaded stents modified with hyaluronic acid and heparin for induction of rapid and tight re-endothelialization.

    PubMed

    Choi, Dong Hoon; Kang, Sung Nam; Kim, Seong Min; Gobaa, Samy; Park, Bang Ju; Kim, Ik Hwan; Joung, Yoon Ki; Han, Dong Keun

    2016-05-01

    Rapid re-endothelialization of damaged vessel lining efficiently prevents restenosis and thrombosis and restores original vascular functions. In this study, we designed a novel metallic stent with a heparin-modified surface and used different methods, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and divinyl sulfone (DVS), to load growth factors. First we loaded heparin into a dopamine-conjugated hyaluronic acid (HA) coating to serve as a growth factor reservoir. In a second step, we took advantage of the heparin-binding domain of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to gain advanced re-endothelialization capabilities. We demonstrated that DVS technique offered higher amount of growth factor loading. In vitro assessment also showed better capillary-like structure formation and localized gap junctions when DVS coating was employed. This study suggested that growth factor loaded stent modified by HA and heparin provided the advantage to rapid and tight restoration of endothelium.

  18. The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture.

    PubMed

    Bian, Shaoquan; He, Mengmeng; Sui, Junhui; Cai, Hanxu; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong

    2016-04-01

    Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine.

  19. High Mesenchymal Stem Cell Seeding Densities in Hyaluronic Acid Hydrogels Produce Engineered Cartilage with Native Tissue Properties

    PubMed Central

    Erickson, Isaac E.; Kestle, Sydney R.; Zellars, Kilief H.; Farrell, Megan J.; Kim, Minwook; Burdick, Jason A.; Mauck, Robert L.

    2012-01-01

    Engineered cartilage based on adult mesenchymal stem cells (MSCs) is an alluring goal for the repair of articular defects. However, efforts to date have failed to generate constructs with sufficient mechanical properties to function in the demanding environment of the joint. Our findings with a novel photocrosslinked hyaluronic acid (HA) hydrogel suggest that stiff gels (high HA concentration, 5% w/vol) foster chondrogenic differentiation and matrix production, but limit overall functional maturation due to the inability of formed matrix to diffuse away from the point of production and form a contiguous network. In the current study, we hypothesized that increasing the MSC seeding density would decrease the required diffusional distance, and so expedite the development of functional properties. To test this hypothesis, bovine MSCs were encapsulated at seeding densities of either 20 or 60 million cells per mL in 1%, 3%, and 5% (w/vol) hyaluronic acid (HA) hydrogels. Counter our hypothesis, higher concentration HA gels (3% and 5%) did not develop more rapidly with increased MSC seeding density. However, the biomechanical properties of low concentration (1%) HA constructs increased markedly (nearly 3-fold with a 3-fold increase in seeding density). To ensure that optimal nutrient access was delivered, we next cultured these constructs under dynamic culture conditions (orbital shaking) for 9 weeks. Under these conditions, 1% HA seeded at 60 million MSCs per mL reached a compressive modulus in excess of 1 MPa (compared to 0.3-0.4MPa for free swelling constructs). This is the highest level we have reported to date in this HA hydrogel system, and represents a significant advance towards functional stem cell-based tissue engineered cartilage. PMID:22546516

  20. Receptor-Meditated Endocytosis by Hyaluronic Acid@Superparamagnetic Nanovetor for Targeting of CD44-Overexpressing Tumor Cells

    PubMed Central

    Yu, Kwang Sik; Lin, Meng Meng; Lee, Hyun-Ju; Tae, Ki-Sik; Kang, Bo-Sun; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Han, Seung-Yun; Kim, Do Kyung

    2016-01-01

    The present report proposes a more rational hyaluronic acid (HA) conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs) by covalently binding the targeting molecules (HA) with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA)@SPIONs was included oxidization of nanoparticle’s surface with H2O2 followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells. Fourier transform infrared (FTIR) and zeta-potential studies confirmed the chemical bonding between amino acid linker and polysaccharides. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed that HA-SPIONs-treated cells remained 82.9% ± 2.7% alive at high particle dosage (200 µg/mL iron concentration), whereas GA-SPIONs and bare SPIONs (B-SPIONs) treated cells had only 59.3% ± 13.4% and 26.5% ± 3.1% survival rate at the same conditions, respectively. Confocal microscopy analysis showed increased cellular internalization of HA-SPIONs compared to non-interacting agarose coated SPIONs (AgA-SPIONs). PMID:28335277

  1. Clinical Efficacy of a Spray Containing Hyaluronic Acid and Dexpanthenol after Surgery in the Nasal Cavity (Septoplasty, Simple Ethmoid Sinus Surgery, and Turbinate Surgery)

    PubMed Central

    2014-01-01

    Background. This prospective, controlled, parallel-group observational study investigated the efficacy of a spray containing hyaluronic acid and dexpanthenol to optimise regular treatment after nasal cavity surgery in 49 patients with chronic rhinosinusitis. Methods. The control group received standard therapy. Mucosal regeneration was determined using rhinoscopy sum score (RSS). Pre- and postoperative nasal patency was tested using anterior rhinomanometry. The participants were questioned about their symptoms. Results. Regarding all RSS parameters (dryness, dried nasal mucus, fibrin deposition, and obstruction), mucosal regeneration achieved good final results in both groups, tending to a better improvement through the spray application, without statistically significant differences during the whole assessment period, the mean values being 7.04, 5.00, 3.66, and 3.00 (intervention group) and 7.09, 5.14, 4.36, and 3.33 (control group). No statistically significant benefit was identified for nasal breathing, foreign body sensation, and average rhinomanometric volume flow, which improved by 12.31% (control group) and 11.24% (nasal spray group). Conclusion. The investigational product may have additional benefit on postoperative mucosal regeneration compared to standard cleaning procedures alone. However, no statistically significant advantage could be observed in this observational study. Double-blind, controlled studies with larger populations will be necessary to evaluate the efficacy of this treatment modality. PMID:25104962

  2. Clinical efficacy of a spray containing hyaluronic Acid and dexpanthenol after surgery in the nasal cavity (septoplasty, simple ethmoid sinus surgery, and turbinate surgery).

    PubMed

    Gouteva, Ina; Shah-Hosseini, Kija; Meiser, Peter

    2014-01-01

    Background. This prospective, controlled, parallel-group observational study investigated the efficacy of a spray containing hyaluronic acid and dexpanthenol to optimise regular treatment after nasal cavity surgery in 49 patients with chronic rhinosinusitis. Methods. The control group received standard therapy. Mucosal regeneration was determined using rhinoscopy sum score (RSS). Pre- and postoperative nasal patency was tested using anterior rhinomanometry. The participants were questioned about their symptoms. Results. Regarding all RSS parameters (dryness, dried nasal mucus, fibrin deposition, and obstruction), mucosal regeneration achieved good final results in both groups, tending to a better improvement through the spray application, without statistically significant differences during the whole assessment period, the mean values being 7.04, 5.00, 3.66, and 3.00 (intervention group) and 7.09, 5.14, 4.36, and 3.33 (control group). No statistically significant benefit was identified for nasal breathing, foreign body sensation, and average rhinomanometric volume flow, which improved by 12.31% (control group) and 11.24% (nasal spray group). Conclusion. The investigational product may have additional benefit on postoperative mucosal regeneration compared to standard cleaning procedures alone. However, no statistically significant advantage could be observed in this observational study. Double-blind, controlled studies with larger populations will be necessary to evaluate the efficacy of this treatment modality.

  3. Preliminary histopathological study of intra-articular injection of a novel highly cross-linked hyaluronic acid in a rabbit model of knee osteoarthritis.

    PubMed

    Iannitti, Tommaso; Elhensheri, Mohamed; Bingöl, Ali O; Palmieri, Beniamino

    2013-04-01

    Osteoarthritis is a degenerative joint disease mostly occurring in the knee and commonly seen in middle-aged and elderly adults. Intra-articular injection of hyaluronic acid has been widely used for treatment of knee osteoarthritis. The aim of this study was to evaluate the efficacy of intra-articular injection of a novel highly cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, on knee articular cartilage in a rabbit model of collagenase-induced knee osteoarthritis. After induction of experimental osteoarthritis by intra-articular injection of collagenase, adult New Zealand white rabbits (n = 12) were divided into 3 groups. Group 1 (control group) received 0.3 ml phosphate buffered saline into the right knee joint. Group 2 received 0.3 ml cross-linked hyaluronic acid (33 mg/ml) into the right knee joint. Group 3 received a mixture of 0.15 ml cross-linked hyaluronic acid (33 mg/ml), 0.05 ml ropivacaine hydrochloride 1 % and 0.1 ml triamcinolone acetonide (10 mg/ml) into the right knee joint. Intra-articular injections were given 4 weeks after first collagenase injection and were administered once a week for 3 weeks. Gross pathology and histological evaluation of rabbits' knee joints were performed after 16 weeks following initial collagenase injection. Histological analysis of sections of right knee joints at lesion sites showed a significant decrease in Mankin's score in groups treated with hyaluronic acid alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide versus control group (p < 0.05 and p < 0.01 respectively). This evidence was consistent with strong articular degenerative changes in control right knee joints (grade III osteoarthritis), while the treated groups revealed less severe articular degenerative changes (grade II osteoarthritis). The present results show that cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and

  4. Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence.

    PubMed

    Braithwaite, Gavin J C; Daley, Michael J; Toledo-Velasquez, David

    2016-01-01

    Hyaluronic acid of various molecular weights has been in use for the treatment of osteoarthritis knee pain for decades. Worldwide, these products are regulated as either as drugs or devices and in some countries as both. In the US, this class of products is regulated as Class III medical devices, which places specific regulatory requirements on developers of these materials under a Pre-Market Approval process, typically requiring data from prospective randomized controlled clinical studies. In 1984 pharmaceutical manufacturers became able to file an Abbreviated New Drug Application for approval of a generic drug, thus establishing standards for demonstrating equivalence to an existing chemical entity. Recently, the first biosimilar, or 'generic biologic', was approved. Biosimilars are biological products that are approved by the FDA because they are 'highly similar' to a reference product, and have been shown to have no clinically meaningful differences from the reference product. For devices, Class II medical devices have a pathway for declaring equivalence to an existing product by filing a 510 k application for FDA clearance. However, until recently no equivalent regulatory pathway was available to Class III devices. In this paper, we consider the critical mechanical performance parameters for intra-articular hyaluronic products to demonstrate indistinguishable characteristics. Analogous to the aforementioned pathways that allow for a demonstration of equivalence, we examine these parameters for an existing, marketed device and compare molecular weight and rheological properties of multiple batches of a similar product. We propose that this establishes a scientific rationale for establishing Class III medical device equivalence.

  5. A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins.

    PubMed

    Fiorica, Calogero; Pitarresi, Giovanna; Palumbo, Fabio Salvatore; Di Stefano, Mauro; Calascibetta, Filippo; Giammona, Gaetano

    2013-11-30

    Atom transfer radical polymerization (ATRP) has been successfully employed to obtain a new derivative of hyaluronic acid (HA) able to change its solubility as a function of external pH and then to be potentially useful for intestinal release of bioactive molecules, included enzymes and proteins. In particular, a macroinitiator has been prepared by linking 2-bromo-2-methypropionic acid (BMP) to the amino groups of ethylenediamino derivative of tetrabutyl ammonium salt of HA (HA-TBA-EDA). This macroinititor, named HA-TBA-EDA-BMP has been used for the ATRP of sodium methacrylate (MANa) using a complex of Cu(I) and 2,2'-bipyridyl (Byp) as a catalyst. The resulting copolymer, named HA-EDA-BMP-MANa, has been characterized by (1)H NMR and size exclusion chromatography (SEC) analyses. A turbidimetric analysis has showed its pH sensitive behavior, being insoluble in simulated gastric fluid but soluble when pH increases more than 2.5. To confirm the ability of HA-EDA-BMP-MANa in protecting peptides or proteins from denaturation in acidic medium, α-chymotrypsin has been chosen as a model of protein molecule and its activity has been evaluated after entrapment into HA-EDA-BMP-MANa chains and treatment under simulated gastric conditions. Finally, cell compatibility has been evaluated by performing a MTS assay on murine dermal fibroblasts cultured with HA-EDA-BMP-MANa solutions.

  6. Development of injectable biocomposites from hyaluronic acid and bioactive glass nano-particles obtained from different sol-gel routes.

    PubMed

    Sohrabi, Mehri; Hesaraki, Saeed; Kazemzadeh, Asghar; Alizadeh, Masoud

    2013-10-01

    Bioactive glass nano-powders with the same chemical composition and different particle characteristics were synthesized by acid-catalyzed (the glass is called BG1) and acid-base catalyzed (BG2) sol-gel processes. Morphological characteristics of powders were determined by TEM and BET methods. The powders were separately mixed with 3% hyaluronic acid solution to form a paste. In vitro reactivity of pastes was determined by soaking them in simulated body fluid. Rheological behaviors of paste in both rotation and oscillation modes were also measured. The results showed that BG1 particles was microporous with mean pore diameter of 1.6 nm and particle size of ~300 nm while BG2 was mesoporous with average pore diameter of 8 and 17 nm and particle size of 20-30 nm. The paste made of BG2 revealed better washout resistance and in vitro apatite formation ability than BG1. According to the rheological evaluations, both pastes exhibited shear thinning but non-thixotropic behavior, meanwhile paste of BG2 had higher viscosity than BG1. The oscillatory tests revealed that the pastes were viscoelastic materials with more viscous nature. Both pastes could be completely injected through standard syringe using low compressive load of 5-50 N. Overall, The biocomposites can potentially be used as bioactive paste for the treatment of hard and even soft tissues.

  7. [Effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn I-Shot) in the treatment of knee osteoarthritis].

    PubMed

    Miśkowiec, Krzysztof; Gądek, Artur; Jurecka, Alicja; Sówka, Justyna; Ślusarski, Jakub; Liszka, Henryk; Wordliczek, Jerzy

    2016-01-01

    Osteoarthritis (OA) is one of the leading causes of disability in the elderly. The changes in the lubricating properties of synovial fluid lead to significant pain and loss of function. Viscosupplementation, in which hyaluronic acid (HA) is injected into the knee joint, has evolved into an important part of our current therapeutic regimen in addressing the patient with knee pain due to OA. Intra-articular HA has proven to be an effective, safe, and tolerable treatment for symptomatic knee OA. In an effort to limit cardiovascular, gastrointestinal and renal safety concerns with COX-2 selective and nonselective NSAIDs and maximize HA efficacy, it is even proposed using HA earlier in the treatment paradigm for knee OA and also as part of a comprehensive treatment strategy. Our study reconfirmed effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis.

  8. New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase.

    PubMed

    Quagliariello, Vincenzo; Armenia, Emilia; Aurilio, Caterina; Rosso, Francesco; Clemente, Ottavia; de Sena, Gabriele; Barbarisi, Manlio; Barbarisi, Alfonso

    2016-08-01

    The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc.

  9. Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a ligand for attachment of group A Streptococcus to CD44 on human keratinocytes.

    PubMed Central

    Schrager, H M; Albertí, S; Cywes, C; Dougherty, G J; Wessels, M R

    1998-01-01

    We used wild-type and isogenic mutant strains of group A Streptococcus (GAS) that expressed M protein, capsule, or both to study the function of M protein and the hyaluronic acid capsular polysaccharide in attachment of GAS to human keratinocytes. Types 6 and 24, but not type 18, M protein were found to mediate attachment of GAS to soft palate or skin keratinocytes, but this interaction was prevented by the hyaluronic acid capsule on highly encapsulated, or mucoid, strains. Monoclonal antibody to CD44, the principal hyaluronic acid-binding receptor on keratinocytes, inhibited attachment of both highly encapsulated and poorly encapsulated wild type strains of GAS, but not the attachment of acapsular mutants. Transfection of K562 cells with cDNA encoding human CD44 conferred the capacity to bind each of six wild-type strains of GAS, but not to bind acapsular mutants. Because, in contrast to other potential adhesins, the group A streptococcal capsule is both highly conserved and surface-exposed, it may serve as a universal adhesin for attachment of diverse strains of GAS to keratinocytes of the pharyngeal mucosa and the skin. PMID:9541502

  10. In vitro release and expansion of mesenchymal stem cells by a hyaluronic acid scaffold used in combination with bone marrow.

    PubMed

    Spoliti, Marco; Iudicone, Paola; Leone, Rossella; De Rosa, Alessandro; Rossetti, Francesca Romana; Pierelli, Luca

    2012-10-01

    Articular cartilage injuries of the knee are difficult to treat due to the poor healing ability of cartilage and conventional treatment methods often give unsatisfactory results. Mesenchymal Stem Cells (MSCs) have generated interest as an alternative source of cells for cartilage tissue engineering due to their chondrogenic potential and their easy isolation from bone marrow. It has been reported that the use of scaffold in cartilage engineering acts as a support for cell adhesion, keeping the cells in the cartilage defects and therefore facilitating tissue formation, and that Hyaluronic acid (HA) is a molecule of particular interest for producing scaffold for tissue engineering. In this study we evaluated the in vitro selection and expansion of Bone Marrow MSCs (BM-MSCs) and by residual BM+HA membrane (BM-HA-MSCs) used as scaffold. Sixty mL of BM have been aspirated by the posterior iliac crest and HA membrane (Hyalograft-C, Fidia Advanced Biopolimers) was used as scaffold. BM-MSCs were cultured with D-MEM supplemented with Desamethasone, Ascorbic Acid, β-Transforming Growth Factor and Insulin. When cultured in chondrogenic selective medium MSCs from both BM and HA membrane were able to differentiate into chondrogenesis, but BM-HA-MSCs showed a higher staining intensity than BM-MSCs when they were stained with Toluidine blue. The interaction of MSCs with the HA-scaffold seems to promote by itself chondrogenesis.

  11. Chromosomal integration of hyaluronic acid synthesis (has) genes enhances the molecular weight of hyaluronan produced in Lactococcus lactis.

    PubMed

    Hmar, Rothangmawi Victoria; Prasad, Shashi Bala; Jayaraman, Guhan; Ramachandran, Kadathur B

    2014-12-01

    Microbial production of hyaluronic acid (HA) is an attractive substitute for extraction of this biopolymer from animal tissues. Natural producers such as Streptococcus zooepidemicus are potential pathogens; therefore, production of HA by recombinant bacteria that are generally recognized as safe (GRAS) organisms is a viable alternative that is being extensively explored. However, plasmid-based expression systems for HA production by recombinant bacteria have the inherent disadvantage of reduced productivity because of plasmid instability. To overcome this problem, the HA synthesis genes (hasA-hasB and hasA-hasB-hasC) from has-operon of S. zooepidemicus were integrated into the chromosome of Lactococcus lactis by site-directed, double-homologous recombination developing strains VRJ2AB and VRJ3ABC. The chromosomal integration stabilized the genes and obviated the instability observed in plasmid-expressed recombinant strains. The genome-integrated strains produced higher molecular weight (3.5-4 million Dalton [MDa]) HA compared to the plasmid-expressed strains (2 MDa). High molecular weight HA was produced when the intracellular concentration of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and uridine diphosphate-glucuronic acid (UDP-GlcUA) was almost equal and hasA to hasB ratio was low. This work suggests an optimal approach to obtain high molecular weight HA in recombinant strains.

  12. Hyaluronic Acid/PLGA Core/Shell Fiber Matrices Loaded with EGCG Beneficial to Diabetic Wound Healing.

    PubMed

    Shin, Yong Cheol; Shin, Dong-Myeong; Lee, Eun Ji; Lee, Jong Ho; Kim, Ji Eun; Song, Sung Hwa; Hwang, Dae-Youn; Lee, Jun Jae; Kim, Bongju; Lim, Dohyung; Hyon, Suong-Hyu; Lim, Young-Jun; Han, Dong-Wook

    2016-12-01

    During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.

  13. Hyaluronic Acid: Perspectives in Upper Aero-Digestive Tract. A Systematic Review

    PubMed Central

    Casale, Manuele; Moffa, Antonio; Sabatino, Lorenzo; Pace, Annalisa; Oliveto, Giuseppe; Vitali, Massimiliano; Baptista, Peter; Salvinelli, Fabrizio

    2015-01-01

    Background To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper aerodigestive tract (UADT). The use of topical drugs, which are able to reduce mucosal inflammation and to improve healing tissues, can represent a relevant therapeutic advance. Topical sodium hyaluronate (SH) has recently been recognized as adjuvant treatment in the chronic inflammatory disease of the UADT. Aims The aim of our work was to review the published literature regarding all the potential therapeutic effects of SH in the chronic inflammatory disease of UADT. Methods Relevant published studies were searched in Pubmed, Google Scholar, Ovid using keywords (“sodium hyaluronate” and “upper airways”) or Medical Subject Headings. Results At the end of our selection process, sixteen publications have been included. Six of them in the post-operative period of nasal-sinus surgery, 2 of them in pediatric patients affected by recurrent upper respiratory tract infections, 4 of them in reducing symptoms and preventing exacerbations of chronic upper airways in adult population, 4 of them in patients with chronic inflammatory disease of UADT, including gastro-esophageal reflux disease (GERD). Conclusions Topical administration of SH plays a pivotkey role in the postoperative phase of patients undergoing FESS and nasal surgery, and positive results are generally observed in all the patients suffering from UADT chronic inflammatory disease. PMID:26120837

  14. Non-surgical treatment of deep wounds triggered by harmful physical and chemical agents: a successful combined use of collagenase and hyaluronic acid.

    PubMed

    Onesti, Maria G; Fino, Pasquale; Ponzo, Ida; Ruggieri, Martina; Scuderi, Nicolò

    2016-02-01

    Some chronic ulcers often occur with slough, not progressing through the normal stages of wound healing. Treatment is long and other therapies need to be performed in addition to surgery. Patients not eligible for surgery because of ASA class (American Society of Anesthesiologists class) appear to benefit from chemical therapy with collagenase or hydrocolloids in order to prepare the wound bed, promoting the healing process. We describe four cases of traumatic, upper limb deep wounds caused by different physical and chemical agents, emphasising the effectiveness of treatment based on topical application of collagenase and hyaluronic acid (HA) before standardised surgical procedures. We performed careful disinfection of lesions combined with application of topical cream containing hyaluronic acid, bacterial fermented sodium hyaluronate (0·2%w/w) salt, and bacterial collagenase obtained from non-pathogenic Vibrio alginolyticus (>2·0 nkat1/g). In one patient a dermo-epidermal graft was used to cover the wide loss of substance. In two patients application of a HA-based dermal substitute was done. We obtained successful results in terms of wound healing, with satisfactory aesthetic result and optimal recovery of the affected limb functionality. Topical application of collagenase and HA, alone or before standardised surgical procedures allows faster wound healing.

  15. Controllably local gene delivery mediated by polyelectrolyte multilayer films assembled from gene-loaded nanopolymersomes and hyaluronic acid

    PubMed Central

    Teng, Wei; Wang, Qinmei; Chen, Ying; Huang, Hongzhang

    2014-01-01

    To explore a spatiotemporally controllable gene delivery system with high efficiency and safety, polyelectrolyte multilayer (PEM) films were constructed on titanium or quartz substrates via layer-by-layer self-assembly technique by using plasmid deoxyribonucleic acid-loaded lipopolysaccharide–amine nanopolymersomes (pNPs) as polycations and hyaluronic acid (HA) as polyanions. pNPs were chosen because they have high transfection efficiency (>95%) in mesenchymal stem cells (MSCs) and induce significant angiogenesis in zebrafish in conventional bolus transfection. The assembly process of PEM films was confirmed by analyses of quartz crystal microbalance with dissipation, X-ray photoelectron spectroscopy, infrared, contact angle, and zeta potential along with atomic force microscopy observation. Quartz crystal microbalance with dissipation analysis reveals that this film grows in an exponential mode, pNPs are the main contributor to the film mass, and the film mass can be modulated in a relatively wide range (1.0–29 μg/cm2) by adjusting the deposition layer number. Atomic force microscopy observation shows that the assembly leads to the formation of a patterned film with three-dimensional tree-like nanostructure, where the branches are composed of beaded chains (pNP beads are strung on HA molecular chains), and the incorporated pNPs keep structure intact. In vitro release experiment shows that plasmid deoxyribonucleic acid can be gradually released from films over 14 days, and the released plasmid deoxyribonucleic acid exists in a complex form. In vitro cell experiments demonstrate that PEM films can enhance the adhesion and proliferation of MSCs and efficiently transfect MSCs in situ in vitro for at least 4 days. Our results suggest that a (pNPs/HA)n system can mediate efficient transfection in stem cells in a spatially and temporally controllable pattern, highlighting its huge potential in local gene therapy. PMID:25378927

  16. Rational design of network properties in guest-host assembled and shear-thinning hyaluronic acid hydrogels.

    PubMed

    Rodell, Christopher B; Kaminski, Adam L; Burdick, Jason A

    2013-11-11

    Shear-thinning hydrogels afford direct injection or catheter delivery to tissues without potential premature gel formation and delivery failure or the use of triggers such as chemical initiators or heat. However, many shear-thinning hydrogels require long reassembly times or exhibit rapid erosion. We developed a shear-thinning hyaluronic acid (HA) hydrogel based on the guest-host interactions of adamantane modified HA (guest macromer, Ad-HA) and β-cyclodextrin modified HA (host macromer, CD-HA). The ability of the guest and host molecules to interact with their counterpart following conjugation to HA was confirmed by (1)H NMR spectroscopy and was similar to that of the native complex. Mixing of Ad-HA and CD-HA resulted in rapid formation of a hydrogel composed of guest-host bonds. The hydrogel physical properties, including mechanics and flow characteristics, were dependent on cross-link density and network structure, which were controlled through macromer concentration, the extent of guest macromer modification, and the molar ratio of guest and host functional groups. The guest-host assembly mechanism permitted both shear-thinning behavior for ease of injection and near-instantaneous reassembly for material retention at the target sight. The hydrogel erosion and release of a model biomolecule were also dependent on design parameters and were sustained for over 60 days. These hydrogels show potential as a minimally invasive injectable hydrogel for biomedical applications.

  17. Fabrication of Novel Hydrogel with Berberine-Enriched Carboxymethylcellulose and Hyaluronic Acid as an Anti-Inflammatory Barrier Membrane

    PubMed Central

    Huang, Yu-Chih; Huang, Kuen-Yu; Yang, Bing-Yuan

    2016-01-01

    An antiadhesion barrier membrane is an important biomaterial for protecting tissue from postsurgical complications. However, there is room to improve these membranes. Recently, carboxymethylcellulose (CMC) incorporated with hyaluronic acid (HA) as an antiadhesion barrier membrane and drug delivery system has been reported to provide excellent tissue regeneration and biocompatibility. The aim of this study was to fabricate a novel hydrogel membrane composed of berberine-enriched CMC prepared from bark of the P. amurense tree and HA (PE-CMC/HA). In vitro anti-inflammatory properties were evaluated to determine possible clinical applications. The PE-CMC/HA membranes were fabricated by mixing PE-CMC and HA as a base with the addition of polyvinyl alcohol to form a film. Tensile strength and ultramorphology of the membrane were evaluated using a universal testing machine and scanning electron microscope, respectively. Berberine content of the membrane was confirmed using a UV-Vis spectrophotometer at a wavelength of 260 nm. Anti-inflammatory property of the membrane was measured using a Griess reaction assay. Our results showed that fabricated PE-CMC/HA releases berberine at a concentration of 660 μg/ml while optimal plasticity was obtained at a 30 : 70 PE-CMC/HA ratio. The berberine-enriched PE-CMC/HA had an inhibited 60% of inflammation stimulated by LPS. These results suggest that the PE-CMC/HA membrane fabricated in this study is a useful anti-inflammatory berberine release system. PMID:28119926

  18. Effect of hyaluronic acid on the regulation of inflammatory mediators in osteoarthritis of the temporomandibular joint: a systematic review.

    PubMed

    Iturriaga, V; Bornhardt, T; Manterola, C; Brebi, P

    2017-05-01

    Osteoarthritis is one of the most frequent pathologies affecting the temporomandibular joint (TMJ). There is evidence that the use of intra-articular hyaluronic acid (HA) for the treatment of this disorder achieves positive effects through a reduction in inflammatory mediators. A systematic review of the available evidence regarding the regulation of inflammatory mediators when applying HA in osteoarthritis of the TMJ in humans was performed. The Web of Science, Embase, ScienceDirect, MEDLINE, Scopus, EBSCOhost, and LILACS databases, SciELO library, and search engine Trip Database were searched systematically. Two thousand eight hundred and sixty-three related articles were found, of which only two met the selection criteria (both were clinical trials and evidence level 2b for treatment studies). These two articles represented a population of 87 patients. Both articles reported that the application of HA had a positive effect on the regulation of inflammatory mediators; the mediators studied were those of the plasminogen activator system and levels of nitric oxide. The limited evidence available suggests that the application of HA regulates various inflammatory mediators in osteoarthritic processes in the TMJ. Nevertheless, further evidence in this regard is required, through the study of specific pathologies of the TMJ, complementing the assessment of clinical parameters with molecular studies, and generating good quality clinical studies with larger sample sizes.

  19. Relevance of charge balance and hyaluronic acid on alginate-chitosan sponge microstructure and its influence on fibroblast growth.

    PubMed

    Orellana, Sandra L; Giacaman, Annesi; Pavicic, Francisca; Vidal, Alejandra; Moreno-Villoslada, Ignacio; Concha, Miguel

    2016-10-01

    The study of biomaterials by electrical charge scaling to explore the role of net charge on biocompatibility and suitability for tissue regeneration has been limited as has the search for products that could improve this first-rate variable. In the present study, we prepared sponges composed of chitosan/alginate (CS/ALG) with or without hyaluronic acid (HA) by mixing polymer stock solutions of different net electric charge ratios (n(+/) n(-) ), and then lyophilizing them to obtain porous materials. The electric charge ratios n(+/) n(-) studied were 0.3, 0.8, 1.0, and 2.5 for CS/ALG and 0.3, 1.0, 1.9, and 3.7 for CS/ALG/HA sponges. Under these conditions a role for net electric charge balance over sponge microstructure rearrangement, protection to dissolution, cellular proliferation, and cell-cell interactions was apparent, effects that were enhanced by copolymer modification with HA. Mass balance, electric charge, and specific products that influence both such as HA, have a potential in biomaterials for wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2537-2543, 2016.

  20. Preparation, characterization, and biocompatibility evaluation of poly(Nɛ-acryloyl-L-lysine)/hyaluronic acid interpenetrating network hydrogels.

    PubMed

    Cui, Ning; Qian, Junmin; Xu, Weijun; Xu, Minghui; Zhao, Na; Liu, Ting; Wang, Hongjie

    2016-01-20

    In the present study, poly(Nɛ-acryloyl-L-lysine)/hyaluronic acid (pLysAAm/HA) interpenetrating network (IPN) hydrogels were successfully fabricated through the combination of hydrazone bond crosslinking and photo-crosslinking reactions. The HA hydrogel network was first synthesized from 3,3'-dithiodipropionate hydrazide-modified HA and polyethylene glycol dilevulinate by hydrazone bond crosslinking. The pLysAAm hydrogel network was prepared from Nɛ-acryloyl-L-lysine and N,N'-bis(acryloyl)-(L)-cystine by photo-crosslinking. The resultant pLysAAm/HA hydrogels had a good shape recovery property after loading and unloading for 1.5 cycles (up to 90%) and displayed a highly porous microstructure. Their compressive moduli were at least 5 times higher than that of HA hydrogels. The pLysAAm/HA hydrogels had an equilibrium swelling ratio of up to 37.9 and displayed a glutathione-responsive degradation behavior. The results from in vitro biocompatibility evaluation with pre-osteoblasts MC3T3-E1 cells revealed that the pLysAAm/HA hydrogels could support cell viability and proliferation. Hematoxylin and eosin staining indicated that the pLysAAm/HA hydrogels allowed cell and tissue infiltration, confirming their good in vivo biocompatibility. Therefore, the novel pLysAAm/HA IPN hydrogels have great potential for bone tissue engineering applications.

  1. Comparison between intrarticular injection of hyaluronic acid, oxygen ozone, and the combination of both in the treatment of knee osteoarthrosis.

    PubMed

    Giombini, A; Menotti, F; Di Cesare, A; Giovannangeli, F; Rizzo, M; Moffa, S; Martinelli, F

    2016-01-01

    This study aimed to compare short-term clinical outcomes between intra-articular injection of hyaluronic acid (HA), oxygen ozone (O2O3), and the combination of both, in patients affected by osteoarthrosis (OA) of the knee. Seventy patients (age 45-75 years) with knee OA were randomized to intra-articular injections of HA (n=23), or O2O3 (n=23) or combined (n=24) one per week for 5 consecutive weeks. KOOS questionnaire and visual analog scale (VAS), before treatment (pre) at the end (post), and at 2 months after treatment ended (follow-up) were used as outcome measures. Analysis showed a significant effect (P < 0.05) of the conditions (pre, post and follow-up) in all parameters of the KOOS score and a significant effect (P < 0.05) of groups (HA, O2O3 and combined) for pain, symptoms, activities of daily living and quality of life. The combined group scores were higher compared to the HA and O2O3 groups, especially at follow-up. The combination of O2O3 and HA treatment led to a significantly better outcome especially at 2-month follow-up compared to HA and O2O3 given separately to patients affected by OA of the knee.

  2. Comparison of cytotoxicity and wound healing effect of carboxymethylcellulose and hyaluronic acid on human corneal epithelial cells

    PubMed Central

    Lee, Jong Soo; Lee, Seung Uk; Che, Cheng-Ye; Lee, Ji-Eun

    2015-01-01

    AIM To investigate the cytotoxic effect on human corneal epithelial cells (HCECs) and the ability to faciliate corneal epithelial wound healing of carboxymethylcellulose (CMC) and hyaluronic acid (HA). METHODS HCECs were exposed to 0.5% CMC (Refresh plus®, Allergan, Irvine, California, USA) and 0.1% and 0.3% HA (Kynex®, Alcon, Seoul, Korea, and Hyalein mini®, Santen, Osaka, Japan) for the period of 30min, and 4, 12, and 24h. Methyl thiazolyl tetrazolium (MTT)-based calorimetric assay was performed to assess the metabolic activity of cellular proliferation and lactate dehydrogenase (LDH) leakage assay to assess the cytotoxicity. Apoptotic response was evaluated with flow cytometric analysis and fluorescence staining with Annexin V and propiodium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. The wound widths were measured 24h after confluent HCECs were scratch wounded. RESULTS The inhibitory effect of human corneal epithelial proliferation and cytotoxicity showed the time-dependent response but no significant effect. Apoptosis developed in flow cytometry and apoptotic cells were demonstrated in fluorescent micrograph. The damaged HCECs were detached from the bottom of the dish and showed the well-developed vacuole formations. Both CMC and HA stimulated reepithehlialization of HCECs scratched, which were more observed in CMC. CONCLUSION CMC and HA, used in artificial tear formulation, could be utilized without any significant toxic effect on HCECs. Both significantly stimulated HCEC reepithelialization of corneal wounds. PMID:25938030

  3. The Effect of Chondroitin Sulphate and Hyaluronic Acid on Chondrocytes Cultured within a Fibrin-Alginate Hydrogel.

    PubMed

    Little, Christopher J; Kulyk, William M; Chen, Xiongbiao

    2014-09-18

    Osteoarthritis is a painful degenerative joint disease that could be better managed if tissue engineers can develop methods to create long-term engineered articular cartilage tissue substitutes. Many of the tissue engineered cartilage constructs currently available lack the chemical stimuli and cell-friendly environment that promote the matrix accumulation and cell proliferation needed for use in joint cartilage repair. The goal of this research was to test the efficacy of using a fibrin-alginate hydrogel containing hyaluronic acid (HA) and/or chondroitin sulphate (CS) supplements for chondrocyte culture. Neonatal porcine chondrocytes cultured in fibrin-alginate hydrogels retained their phenotype better than chondrocytes cultured in monolayer, as evidenced by analysis of their relative expression of type II versus type I collagen mRNA transcripts. HA or CS supplementation of the hydrogels increased matrix glycosaminoglycan (GAG) production during the first week of culture. However, the effects of these supplements on matrix accumulation were not additive and were no longer observed after two weeks of culture. Supplementation of the hydrogels with CS or a combination of both CS and HA increased the chondrocyte cell population after two weeks of culture. Statistical analysis indicated that the HA and CS treatment effects on chondrocyte numbers may be additive. This research suggests that supplementation with CS and/or HA has positive effects on cartilage matrix production and chondrocyte proliferation in three-dimensional (3D) fibrin-alginate hydrogels.

  4. Use of Platelet Rich Plasma and Hyaluronic Acid in the Treatment of Complications of Achilles Tendon Reconstruction

    PubMed Central

    Gentile, Pietro; De Angelis, Barbara; Agovino, Annarita; Orlandi, Fabrizio; Migner, Alessandra; Di Pasquali, Camilla; Cervelli, Valerio

    2016-01-01

    BACKGROUND The platelet-rich plasma (PRP) and hyaluronic acid (HA) constitute a system of tissue growth that can regenerate damaged tissue. This study was performed to evaluate the effect of PRP and HA in treatment of complications of Achilles tendon reconstruction. METHODS We selected ten patients affected by Achilles tendon injuries resulting from post-surgical complications subsequent to tenorrhaphy and have treated them with autologous PRP in combination with HA to evaluate the improvement of lesions with wound closure. RESULTS The treatment with PRP and HA for post-surgical complications of Achilles tendon was effective in healing and regeneration of soft and hard tissues. The healing time was shortened, and the treated area preserved a satisfying strength in plantar flexion and extension of the ankle, denoting to a decisive improvement in texture and a more rapid healing and a good cutaneous elasticity, with a significant reduction of the costs of hospitalization and the pain already the immediate postoperatively. The functional rehabilitation in terms of deambulation and joint mobility was complete. CONCLUSION The treatment we proposed allowed an easier and more rapid wound closure with excellent aesthetic improvement. Furthermore, the minimally invasive technique is well tolerated by patients. PMID:27579267

  5. Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering.

    PubMed

    Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Rigogliuso, Salvatrice; Ghersi, Giulio; Giammona, Gaetano

    2013-07-01

    In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control.

  6. Laser sintered porous polycaprolacone scaffolds loaded with hyaluronic acid and gelatin-grafted thermoresponsive hydrogel for cartilage tissue engineering.

    PubMed

    Lee, Ming-Yih; Tsai, Wen-Wei; Chen, His-Jung; Chen, Jyh-Ping; Chen, Chih-Hao; Yeh, Wen-Lin; An, Jia

    2013-01-01

    The aim of this study is to evaluate a soft/hard bi-phase scaffold for cartilage tissue engineering. Chondrocyte proliferation, glycoaminoglycan production and total collagen content are compared between laser-sintered porous polycaprolactone (PCL) scaffolds with and without a thermoresponsive hydrogel grafted with hyaluronic acid and gelatin. The in vitro results show that scaffolds loaded with hydrogel have a higher initial chondrocyte attachment than PCL scaffolds. At day 21 and 28, scaffolds loaded with hydrogel have a significantly higher glycosaminoglycan (GAG) production than PCL scaffolds alone, and total collagen content including collagen type II in the hydrogel-loaded group is three times higher than the group without hydrogel. It is concluded that the laser-sintered porous PCL scaffold has good cytocompatibility, and that the hydrogel phase is able to enhance initial chondrocytes attachment as well as GAG and collagen production of chondrocytes. This study suggests that a soft/hard bi-phase scaffold may be used for cartilage tissue engineering to enhance in vitro chondrogenesis.

  7. Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity

    PubMed Central

    Tang, Tommy Hing-Cheung; Alonso, Sylvie; Ng, Lisa Fong-Poh; Thein, Tun-Linn; Pang, Vincent Jun-Xiong; Leo, Yee-Sin; Lye, David Chien-Boon; Yeo, Tsin-Wen

    2017-01-01

    Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-α, IL-6, IL-10) were measured on enrollment and convalescence. Patients were diagnosed as dengue fever (DF, n = 30), dengue hemorrhagic fever (DHF, n = 20) and non-dengue (ND) febrile illness (n = 11). Acute HA and HS levels were significantly higher in all dengue patients compared to ND (p = 0.0033 and p = 0.0441 respectively), but not different between DF and DHF (p = 0.3426 and p = 0.9180 respectively). Enrolment HA inversely correlated with serum albumin, protein and platelets in all dengue and DHF (p < 0.05). HA and HS in all dengue patients decreased significantly at convalescence. Serum IL-10 was significantly associated with HA in all dengue patients (p = 0.002). Serum HA and HS levels were increased in adult dengue and HA was associated with markers of disease severity. Endothelial glycocalyx damage may have a role in vascular leakage in dengue. PMID:28393899

  8. Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs.

    PubMed

    El Kechai, Naila; Bochot, Amélie; Huang, Nicolas; Nguyen, Yann; Ferrary, Evelyne; Agnely, Florence

    2015-06-20

    The aim of this work was to thoroughly study the effect of liposomes on the rheological and the syringeability properties of hyaluronic acid (HA) hydrogels intended for the local administration of drugs by injection. Whatever the characteristics of the liposomes added (neutral, positively or negatively charged, with a corona of polyethylene glycol chains, size), the viscosity and the elasticity of HA gels increased in a lipid concentration-dependent manner. Indeed, liposomes strengthened the network formed by HA chains due to their interactions with this polymer. The nature and the resulting effects of these interactions depended on liposome composition and concentration. The highest viscosity and elasticity were observed with liposomes covered by polyethylene glycol chains while neutral liposomes displayed the lowest effect. Despite their high viscosity at rest, all the formulations remained easily injectable through needles commonly used for local injections thanks to the shear-thinning behavior of HA gels. The present study demonstrates that rheological and syringeability tests are both necessary to elucidate the behavior of such systems during and post injection. In conclusion, HA liposomal gels appear to be a promising and versatile formulation platform for a wide range of applications in local drug delivery when an injection is required.