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Sample records for hyaluronic acid volumizing

  1. Body shaping and volume restoration: the role of hyaluronic acid.

    PubMed

    Hedén, Per; Sellman, Gabriella; von Wachenfeldt, Mats; Olenius, Michael; Fagrell, Dan

    2009-05-01

    Driven by the rising popularity of minimally invasive techniques, the demand for cosmetic procedures is increasing. Cosmetic body-shaping procedures can be categorized into those that remove tissue and those that add volume. This review focuses on the latter of these categories, particularly on the use of resorbable hyaluronic acid gels specifically developed for minimally invasive volume enhancement. Pilot studies of hyaluronic acid involving its injection to contour various body deformities and its recent use in female breast augmentation are discussed. Injectable hyaluronic acid is effective and well tolerated. It represents an attractive treatment option for volume restoration or augmentation by providing predictable long-lasting results after minimally invasive administration. Alternative treatment options for volume enhancement also are summarized including fat transfer, silicone implants, and the use of injectable nonresorbable products such as silicone, polyalkylimide, and polyacrylamide gels. As patients continue to opt for nonsurgical procedures that offer predictable results, the development of minimally invasive products such as hyaluronic acid is increasingly important. PMID:19280248

  2. Treatment of Age-related Mid-face Atrophy by Injection of Cohesive Polydensified Matrix Hyaluronic Acid Volumizer

    PubMed Central

    Micheels, Patrick; Kravtsov, Maria

    2015-01-01

    Objective: Cohesive Polydensified Matrix® Hyaluronic Acid Volumizer is designed to be injected subcutaneously or in deeper soft tissue layers to restore facial volumes. This post-marketing clinical follow-up was performed to confirm the safety and effectiveness of the product up to 18 months. Design: Injections were performed according to standard clinical practice and patients were followed-up at Months 1, 3, 6, 9, 12, and optionally at Month 18. Effectiveness measures included facial volume loss scale, global aesthetic improvement scale and patients’ satisfaction. Injection site reactions were recorded to evaluate safety. Results: Twenty patients with intermediate-to-severe volume loss in the lateral cheek hollows and/or cheekbone area were treated. Facial volume loss scale scores dropped significantly from a mean value of 3.1 at baseline to 1.3 at Day 1. Significant volume enhancement was maintained at each follow-up visit with mean scores ranging from 1.3 at Month 1 to 1.8 at Month 12. Investigators’ global aesthetic improvement scale assessment showed that up to Month 6 at least 94 percent of patients were rated as “very much improved” or “much improved.” At Month 9, all patients still showed a benefit of treatment with 81 percent rated as “very much” or “much improved” and 19 percent as “improved.” Patients’ evaluation was consistent with investigators’ results. A few expected transient injection site reactions of mild-to-moderate intensity were reported immediately after treatment. These reactions were considered related to the injection procedure, rather than the product. Conclusion: Cohesive Polydensified Matrix Hyaluronic Acid Volumizer is safe and effective for mid-face volume augmentation lasting up to Month 12 and most probably up to Month 18. The aesthetic effect was demonstrated by the effectiveness evaluations and high patient satisfaction. PMID:25852812

  3. Secondary rhinoplasty fixations with hyaluronic acid.

    PubMed

    Liapakis, Ioannis E; Englander, Miriam; Vrentzos, Nikolaos P; Derdas, Stavros P; Paschalis, Eleftherios I

    2013-09-01

    The management of nasal deformities especially after rhinoplasty is a challenge. Postsurgical edema may last 6-8 months, causing aesthetic irregularities and nose deformities. The aim of this study is to present the correction of minor nose deformities secondary to rhinoplasty using hyaluronic acid subdermal injections. Eleven patients were treated between 2009 and 2011 with subdermal injections of hyaluronic acid (24 mg/mL) with 0.3% lidocaine (Juvederm, Allergan, Pringy-France) at the 1-month follow-up visit. The volume of hyaluronic acid injected varied from 0.4 to 1 mL according to the deformity. Injections were aimed to correct minor surface irregularities and to provide aesthetic symmetry. These patients were followed for at least 12 months postoperatively. Irregularities were aesthetically corrected immediately after hyaluronic acid injections. No complications were reported with the exception of minor swelling that resolved within 1 week. Esthetic correction was achieved in all patients as determined by the surgeon as well as by overall patient's satisfaction. Our 1-year follow-up data suggest that hyaluronic acid absorption is slow enough to provide the necessary time for postsurgical edema resorption. Rhinoplasty is among the most commonly used procedures for aesthetic improvement in men and women. However, achievement of the final outcome may take several months due to the induced postsurgical edema. Subdermal hyaluronic acid injections can provide temporary correction of these nose irregularities. Our data suggest that subdermal hyaluronic acid injections may provide immediate and long-lasting correction of these minor deformities. As a result, the aesthetic outcome is achieved and maintained throughout the postsurgical course of edema decompression. PMID:23992166

  4. 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

  5. The role of hyaluronic acid in biomineralization

    NASA Astrophysics Data System (ADS)

    Chen, Zhen-Hua; Ren, Xiu-Li; Zhou, Hui-Hui; Li, Xu-Dong

    2012-12-01

    Hyaluronic acid has been extensively investigated due to intrinsic properties of natural origin and strong ability to bind ions in water. Hyaluronic acid is an excellent crystal modifier because its abundant negatively charged carboxyl groups can bind the cations protruding from the crystal lattice. In this review, we mainly present the latest work focus on the role of hyaluronic acid in controlling the crystallization, breaking the symmetry of crystal, and the surface funtionalization of nanocrystals.

  6. A Multicenter, Single-Blind Randomized, Controlled Study of a Volumizing Hyaluronic Acid Filler for Midface Volume Deficit: Patient-Reported Outcomes at 2 Years

    PubMed Central

    Few, Julius; Cox, Sue Ellen; Paradkar-Mitragotri, Deepali; Murphy, Diane K.

    2015-01-01

    Background Juvéderm Voluma XC is a volumizing hyaluronic acid filler used for correction of age-related midface volume deficit (MVD). Objectives The effectiveness of Juvéderm Voluma XC was examined from the patient perspective. Methods Patients with moderate to severe age-related MVD (N = 235) received Juvéderm Voluma XC. At quarterly follow-up visits for 2 years, patients rated treatment outcomes on the Global Aesthetic Improvement Scale (GAIS), overall satisfaction with facial appearance, satisfaction with midfacial regions, achievement of treatment goal, Look and Feel of the Midface (LAFM), and Self-Perception of Age (SPA). Patients recorded treatment-site responses in 30-day diaries. Results At 6 months and 2 years after treatment, 92.8% and 79.0% of patients, respectively, rated their cheek volume as improved/much improved on the GAIS. Improvement in satisfaction with facial appearance was noted by 89.8% of patients at 6 months and 75.8% at 2 years. Increased satisfaction with outer and lower cheek areas and cheek-bone projection and clinically significant improvements in LAFM were noted through month 24. Treatment goals were achieved by 67.8% of patients at 6 months and 49.0% at 2 years. Patients reported looking, on average, 5 years younger at 6 months and 3 years younger at 2 years. The most common treatment site responses were tenderness, swelling, firmness, and lumps/bumps; most were mild to moderate in severity and lasted ≤2 weeks. Conclusions Juvéderm Voluma XC for age-related MVD is effective and well-tolerated from the patient perspective, with results lasting up to 2 years. Level of Evidence 4 Therapeutic PMID:25964628

  7. The potpourri approach to hyaluronic acid filler injections.

    PubMed

    Lim, Adrian C

    2010-02-01

    There is an ever-expanding range of hyaluronic acid fillers with varying physical characteristics available to cosmetic dermatologists. These fillers are commercially packaged in syringes of approximately 1 mL (range 0.5-2 mL) volume. Filler injectors are currently qualitatively and quantitatively restricted to fillers packaged in ready-to-go syringes. Patients often present for pan-facial rejuvenation requiring varying amounts of fillers as well as more than one type/subtype of filler for optimum correction. The potpourri approach allows access to a range of prepared hyaluronic acid filler subtypes that can be used on the same patient in the one session. The potpourri method centres on the use of multiple 31-gauge insulin syringes prepared with a range of different hyaluronic acid filler products that are ready for use. This increases flexibility with filler selection and has the potential to provide better filler-to-tissue match for patients. PMID:20148852

  8. Ions in hyaluronic acid solutions

    NASA Astrophysics Data System (ADS)

    Horkay, Ferenc; Basser, Peter J.; Londono, David J.; Hecht, Anne-Marie; Geissler, Erik

    2009-11-01

    Hyaluronic acid (HA) is an anionic biopolymer that is almost ubiquitous in biological tissues. An attempt is made to determine the dominant features that account for both its abundance and its multifunctional role, and which set it apart from other types of biopolymers. A combination of osmotic and scattering techniques is employed to quantify its dynamic and static properties in near-physiological solution conditions, where it is exposed both to mono- and divalent counterions. An equation of state is derived for the osmotic pressure Π in the semidilute concentration region, in terms of two variables, the polymer concentration c and the ionic strength J of the added salt, according to which Π =1.4×103c9/4/J3/4 kPa, where c and J are expressed in mole. Over the physiological ion concentration range, the effect of the sodium chloride and calcium chloride on the osmotic properties of HA solutions is fully accounted for by their contributions to the ionic strength. The absence of precipitation, even at high CaCl2 concentrations, distinguishes this molecule from other biopolymers such as DNA. Dynamic light scattering measurements reveal that the collective diffusion coefficient in HA solutions exceeds that in aqueous solutions of typical neutral polymers by a factor of approximately 5. This property ensures rapid adjustment to, and recovery from, stress applied to HA-containing tissue. Small angle x-ray scattering measurements confirm the absence of appreciable structural reorganization over the observed length scale range 10-1000 Å, as a result of calcium-sodium ion exchange. The scattered intensity in the transfer momentum range q >0.03 Å-1 varies as 1/q, indicating that the HA chain segments in semidilute solutions are linear over an extended concentration range. The osmotic compression modulus c ∂Π/∂c, a high value of which is a prerequisite in structural biopolymers, is several times greater than in typical neutral polymer solutions.

  9. 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. PMID:26311237

  10. 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. PMID:26505539

  11. Advances and Refinement in Hyaluronic Acid Facial Fillers.

    PubMed

    Costa, Christopher R; Kordestani, Reza; Small, Kevin H; Rohrich, Rod J

    2016-08-01

    Fillers temporarily augment deflated or ptotic facial compartments to restore a youthful appearance. Hyaluronic acids predominate the fillers market because of their focal volumization, duration of effect, low incidence of adverse reactions, and reversibility. Being able to properly perform these in-office procedures will ensure safety for patients and provide aesthetically optimal results. This communication provides the senior author's (R.J.R.) stepwise approach to facial aging and deflation with soft-tissue injectable fillers. PMID:27465184

  12. 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

  13. Hyaluronic Acid Fillers: Science and Clinical Uses.

    PubMed

    Gutowski, Karol A

    2016-07-01

    Hyaluronic acid soft tissue fillers include a range of products (Juvederm Ultra, Juvederm Ultra Plus, Voluma, Restylane Silk, Restylane, Restylane Lyft, and Belotero Balance) that are used commonly for facial rejuvenation and enhancement of facial features. Although these products are similar in many ways, they are not interchangeable and have unique characteristics that need to be considered. Injection sites and techniques for facial rejuvenation are discussed. PMID:27363762

  14. 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.

  15. Binding of oligosaccharides of hyaluronic acid to proteoglycans (Short Communication)

    PubMed Central

    Hardingham, Timothy E.; Muir, Helen

    1973-01-01

    Oligosaccharides derived from hyaluronic acid were shown to inhibit proteoglycan–hyaluronic acid interaction, as measured in a viscometer. The relative inhibition increased with the size of the oligosaccharide and the results suggested that decasaccharides were the smallest fragments able to bind strongly to the proteoglycan. PMID:4273187

  16. 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. PMID:14671664

  17. The effect of hyaluronic acid on brushite cement cohesion.

    PubMed

    Alkhraisat, M H; Rueda, C; Mariño, F T; Torres, J; Jerez, L B; Gbureck, U; Cabarcos, E L

    2009-10-01

    The improvement of calcium phosphate cement (CPC) cohesion is essential for its application in highly blood perfused regions. This study reports the effectiveness of hyaluronic acids of different molecular weights in the enhancement of brushite cement cohesion. The cement was prepared using a powder phase composed of a mixture of beta-tricalcium phosphate and monocalcium phosphate monohydrate, whereas the liquid phase was formed by 0.5M citric acid solution modified by the addition of hyaluronic acid of different molecular weights. It was found that medium and high molecular weight hyaluronic acid enhances the cement cohesion and scarcely affects the cement mechanical properties. However, concentrations >0.5% (w/v) were less efficient to prevent the cement disintegration. It is concluded that hyaluronic acid could be applied efficiently to reduce brushite cement disintegration. PMID:19409871

  18. Hyaluronic Acid in Inflammation and Tissue Regeneration.

    PubMed

    Litwiniuk, Malgorzata; Krejner, Alicja; Speyrer, Marcus S; Gauto, Anibal R; Grzela, Tomasz

    2016-03-01

    Hyaluronic acid (HA), the main component of extracellular matrix, is considered one of the key players in the tissue regeneration process. It has been proven to modulate via specific HA receptors, inflammation, cellular migration, and angiogenesis, which are the main phases of wound healing. Studies have revealed that most HA properties depend on its molecular size. High molecular weight HA displays anti-inflammatory and immunosuppressive properties, whereas low molecular weight HA is a potent proinflammatory molecule. In this review, the authors summarize the role of HA polymers of different molecular weight in tissue regeneration and provide a short overview of main cellular receptors involved in HA signaling. In addition, the role of HA in 2 major steps of wound healing is examined: inflammation and the angiogenesis process. Finally, the antioxidative properties of HA are discussed and its possible clinical implication presented. PMID:26978861

  19. 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.

  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. PMID:25078662

  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. Effect of hyaluronic acid on chondrocyte apoptosis

    PubMed Central

    Barreto, Ronald Bispo; Sadigursky, David; de Rezende, Marcia Uchoa; Hernandez, Arnaldo José

    2015-01-01

    OBJECTIVE: To determine the percentage of apoptotic cells in a contusion model of osteoarthritis (OA) and to assess whether intra-articular injection of high doses of hyaluronic acid (HA) immediately after trauma reduces chondrocyte apoptosis. METHODS: Forty knees from adult rabbits were impacted thrice with a 1 kg block released through a 1 meter tall cylinder (29.4 Joules). Subsequently, 2 mL of HA was injected in one knee and 2 mL saline in the contra-lateral knee. Medication were administered twice a week for 30 days, when animals were sacrificed. Specimens were prepared for optical microscopy exam and terminal deoxynucleotidyl transferase end labeling assay (TUNEL). RESULTS: The apoptosis rate in the contusion model was 68.01% (± 19.73%), a higher rate than previously described. HA significantly reduced the rate of apoptosis to 53.52% (± 18.09) (p <0.001). CONCLUSION: Intra-articular HA administration started immediately after trauma reduces impact-induced chondrocyte apoptosis rates in rabbits. Level of Evidence I, Experimental Study. PMID:27069407

  3. 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

  4. Comprehensive Treatment of Periorbital Region with Hyaluronic Acid.

    PubMed

    Bravo, Bruna Souza Felix; Rocha, Camila Roos Mariano Da; Bastos, Julien Toni De; Silva, Priscila Mara Chaves E

    2015-06-01

    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

  5. 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

  6. 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.

  7. Chemical functionalization of hyaluronic acid for drug delivery applications.

    PubMed

    Vasi, Ana-Maria; Popa, Marcel Ionel; Butnaru, Maria; Dodi, Gianina; Verestiuc, Liliana

    2014-05-01

    Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H(1) NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications. PMID:24656366

  8. Hyaluronic acid filler injections with a 31-gauge insulin syringe.

    PubMed

    Lim, Adrian C

    2010-02-01

    Hyaluronic acid gel is a commonly used skin/soft tissue filler in cosmetic dermatology. Hyaluronic acid fillers are packaged in proprietary luer-lock syringes that can be injected via a 30-gauge, 27-gauge or larger diameter needle depending on the consistency of the gel. A method of decanting proprietary hyaluronic acid fillers into multiple 31-gauge insulin syringes for injection is described. The use of a 31-gauge insulin syringe for filler injections can potentially enhance the injection process through more accurate product delivery and placement. This has the potential to produce a more balanced and symmetrical outcome for patients. Additional benefits include less injection pain, less bleeding/bruising and higher levels of patient satisfaction. PMID:20148851

  9. 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. PMID:26433240

  10. 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. PMID:17936350

  11. Nicolau syndrome due to hyaluronic acid injections.

    PubMed

    Andre, Pierre; Haneke, Eckart

    2016-08-01

    Six cases of vascular compromise after hyaluronic injection are reported. Clinical symptoms realized a Nicolau syndrome, which is characterized by immediate pain, livedoid pattern and a few days later by the appearance of scabs and skin necrosis. This type of complication is rare, but may be dramatic and injectors must be aware of that. A thorough knowledge of facial anatomy is mandatory to avoid the risky facial areas. The use of a flexible cannula instead of a sharp needle has much less risk of hurting vessels and must be preferred. The support of the patient is discussed and a treatment protocol is proposed. PMID:26963701

  12. Productivity of concentrated hyaluronic acid using a Maxblend fermentor.

    PubMed

    Hasegawa, S; Nagatsuru, M; Shibutani, M; Yamamoto, S; Hasebe, S

    1999-01-01

    Application of the Maxblend impeller to the fermentative production of hyaluronic acid (HA) was investigated. A 2-m3-scale fermentor fitted with this impeller (MBF) was used and the main fermentation was started with 85% of the nominal volume containing the pre-culture broth and medium. The kinetic characteristics of the MBF were compared with those of a conventional-type fermentor fitted with a turbine blade (TBN). The HA production yield in the MBF was over 20% higher than that in the TBN under the operating conditions of a high aeration rate and low vessel pressure since the broth viscosity increased. The apparent viscosity of the broth at the end of the cultivation rose to about 70 Pa.s. The molecular weight of the HA produced was independent of the agitation speed within the investigated range, and no significant difference was observed between the viscosity-average molecular weights of the HA obtained in the two types of fermentor, each having an estimated value of 4.3 x 10(6) under the same agitation power. PMID:16232576

  13. Hyaluronic acid gel fillers in the management of facial aging

    PubMed Central

    Brandt, Fredric S; Cazzaniga, Alex

    2008-01-01

    Time affects facial aging by producing cellular and anatomical changes resulting in the consequential loss of soft tissue volume. With the advent of new technologies, the physician has the opportunity of addressing these changes with the utilization of dermal fillers. Hyaluronic acid (HA) dermal fillers are the most popular, non-permanent injectable materials available to physicians today for the correction of soft tissue defects of the face. This material provides an effective, non invasive, non surgical alternative for correction of the contour defects of the face due to its enormous ability to bind water and easiness of implantation. HA dermal fillers are safe and effective. The baby-boomer generation, and their desire of turning back the clock while enjoying an active lifestyle, has expanded the popularity of these fillers. In the US, there are currently eight HA dermal fillers approved for commercialization by the Food and Drug Administration (FDA). This article reviews the innate properties of FDA-approved HA fillers and provides an insight on future HA products and their utilization for the management of the aging face. PMID:18488885

  14. 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.

  15. Chemical Sintering Generates Uniform Porous Hyaluronic Acid Hydrogels

    PubMed Central

    Cam, Cynthia; Segura, Tatiana

    2014-01-01

    Implantation of scaffolds for tissue repair has been met with limited success primarily due to the inability to achieve vascularization within the construct. Many strategies have shifted to incorporate pores into these scaffolds to encourage rapid cellular infiltration and subsequent vascular ingrowth. We utilized an efficient chemical sintering technique to create a uniform network of polymethyl methacrylate (PMMA) microspheres for porous hyaluronic acid hydrogel formation. The porous hydrogels generated from chemical sintering possessed comparable pore uniformity and interconnectivity as the commonly used non- and heat sintering techniques. Moreover, similar cell response to the porous hydrogels generated from each sintering approach was observed in cell viability, spreading, proliferation in vitro, as well as, cellular invasion in vivo. We propose chemical sintering of PMMA microspheres using a dilute acetone solution as an alternative method to generating porous hyaluronic acid hydrogels since it requires equal or ten-fold less processing time as the currently used non-sintering or heat sintering technique, respectively. PMID:24120847

  16. Effectiveness and utility of hyaluronic acid in osteoarthritis

    PubMed Central

    Migliore, Alberto; Procopio, Simone

    2015-01-01

    Summary Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and progressive functional limitation. Viscosupplementation with intra-articular hyaluronic acid is a treatment option in knee OA that is included in the professional guidelines for treatment of this joint disease, but potentially should apply to all synovial joints in order to reduce pain and improve joint lubrication. Exogenous HA can enhance chondrocyte HA synthesis, prevent the degradation of cartilage and promote its regeneration. Moreover it can reduce the production of proinflammatory mediators and matrix metalloproteinases involved in OA pathogenesis. This mini review highlights the evidence of hyaluronic acid in reducing osteoarthritis symptoms and structural damage, as well as its ability to delay prosthetic surgery. Viscosupplementation should be considered as a long-term therapy. PMID:26136793

  17. 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.

  18. 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

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

    PubMed

    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. [Biocompatibility analysis of hyaluronic acid sodium gels for medical application].

    PubMed

    Wang, Yaning; Yuan, Tun; Jia, Lifang; Zou, Wen; Liang, Jie

    2012-08-01

    Hyaluronan acid sodium gels are used in ophthalmic surgery, orthopedic treatment and cosmetic surgery. In 2009,there were 12 domestic manufacturers in China producing 33 kinds of products. 23 kinds of imported products were allowed by SFDA to sale in the meantime. Since manufacturers use different production processes, product performances are quite different. According to the GB/T 16886. 1-2001, we designed a pilot program to evaluate the sodium hyaluronate gel products comprehensively in this paper. The results showed that, except chromosome aberration test of gel A and subchronic systemic toxicity of gel C appeared positive, the remaining samples of the test results were negative. This article provides a reference to write standard of cross-linked hyaluronic sodium gel and the revision of standard YY0308-2004. PMID:23016423

  1. Synthesis of hyaluronic acid oligosaccharides and exploration of a fluorous-assisted approach.

    PubMed

    Macchione, Giuseppe; de Paz, José L; Nieto, Pedro M

    2014-07-23

    The synthesis of hyaluronic acid oligomers (tri- and tetrasaccharide) is described. We have followed a pre-glycosylation oxidation strategy. Glucuronic acid units were directly employed in coupling reactions with suitably protected glucosamine derivatives. In order to simplify the purification of synthetic intermediates, a fluorous-assisted strategy has been also explored. Using this approach, a hyaluronic acid trisaccharide was prepared. PMID:24930061

  2. 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.

  3. [Non perforating trabecular surgery with reticulated hyaluronic acid implant].

    PubMed

    Robe-Collignon, N J; Collignon-Brach, J D

    2000-01-01

    Non perforating trabecular surgery (NPTS) with reticulated hyaluronic acid implant (Skgel) allows aqueous humor to leave anterior chamber through a thin trabeculo-Descemet's membrane into a sclerocorneal space filled with Skgel implant and then via the outflow physiological channels. Good intraocular pressure results are obtained with less or without external filtration decreasing the incidence of per- and postoperative complications found after trabeculectomy. This surgery is actually only indicated for primary open angle glaucoma, the trabeculectomy still remaining the gold standard procedure for the other glaucoma cases. PMID:11262887

  4. Hyaluronic acid lipoate: synthesis and physicochemical properties.

    PubMed

    Picotti, Fabrizio; Fabbian, Matteo; Gianni, Rita; Sechi, Alessandra; Stucchi, Luca; Bosco, Marco

    2013-03-01

    The synthesis and physicochemical characterisation of mixed lipoic and formic esters of hyaluronan (Lipohyal) are presented in this paper. The synthesis was conducted by activating lipoic acid with 1,1'-carbonyldiimidazole to obtain lipoyl imidazolide, which reacted with hyaluronan (HA) in formamide under basic conditions. This procedure allows researchers to modulate easily the degree of substitution over a range of 0.05-1.8. Radical scavenger properties were analysed by UV-vis spectroscopy, where improved performance was demonstrated for Lipohyal with respect to the HA row material and lipoic acid. The chemical modification also causes HA to show an improved resistance to hyaluronidase digestion. These findings show that Lipohyal is a highly interesting derivative for applications in the tricological and dermo-cosmetic field and as an anti-aging ingredient. Moreover, Lipohyal can be easily crosslinked by UV irradiation, resulting in an innovative hydrogel with distinctive viscoelastic properties that is suitable as both a dermal-filler and as an intra-articular medical device. PMID:23465930

  5. Characterization of low-molecular-weight hyaluronic acid-based hydrogel and differential stem cell responses in the hydrogel microenvironments.

    PubMed

    Kim, Jungju; Park, Yongdoo; Tae, Giyoong; Lee, Kyu Back; Hwang, Chang Mo; Hwang, Soon Jung; Kim, In Sook; Noh, Insup; Sun, Kyung

    2009-03-15

    Hyaluronic acid is a natural glycosaminoglycan involved in biological processes. Low-molecular-weight hyaluronic acid (10 and 50 kDa)-based hydrogel was synthesized using derivatized hyaluronic acid. Hyaluronic acid was acrylated by two steps: (1) introduction of an amine group using adipic acid dihydrazide, and (2) acrylation by N-acryloxysuccinimide. Injectable hyaluronic acid-based hydrogel was prepared by using acrylated hyaluronic acid and poly(ethylene glycol) tetra-thiols via Michael-type addition reaction. Mechanical properties of the hydrogel were evaluated by varying the molecular weight of acrylated hyaluronic acid (10 and 50 kDa) and the weight percent of hydrogel. Hydrogel based on 50-kDa hyaluronic acid showed the shortest gelation time and the highest complex modulus. Next, human mesenchymal stem cells were cultured in cell-adhesive RGD peptide-immobilized hydrogels together with bone morphogenic protein-2 (BMP-2). Cells cultured in the RGD/BMP-2-incorporated hydrogels showed proliferation rates higher than that of control or RGD-immobilized hydrogels. Real-time RT-PCR showed that the expression of osteoblast marker genes such as CBFalpha1 and alkaline phosphatase was increased in hyaluronic acid-based hydrogel, and the expression level was dependent on the molecular weight of hyaluronic acid, RGD peptide, and BMP-2. This study indicates that low-molecular-weight hyaluronic acid-based hydrogel can be applied to tissue regeneration as differentiation guidance materials of stem cells. PMID:18384163

  6. 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.

  7. Anatomic and mechanical considerations in restoring volume of the face with use of hyaluronic acid fillers with a novel layered technique

    PubMed Central

    Thomas, Mohan K.; Dsilva, James A.; Borole, Ateesh J.; Naik, Sudhir M.; Sarkar, Soma G.

    2014-01-01

    Context: Facial fillers have revolutionized the field of cosmetic facial rejuvenation as it has become the prime sought – after rejuvenation procedure offering youthful, 3-dimensional look with minimal invasiveness. Fillers are expensive and need to be redone periodically hence a sound understanding of structural basis on which they are laid is important in reducing the quantity of filler required in each sitting as well as increasing the longevity of results. Aim: The aim of the following study is to analyse a novel method of facial filling “The pillars pyramids and tie beams (PPT)” technique and its advantages over the conventional methods. Subjects and Methods: A novel technique of injecting the facial fillers was employed on 67 patients visiting our clinic. These patients were followed-up for a period of 3 years. Results: We observed that the amount of filler material required in initial sitting remains the same, however the frequency of touch up visits is decreased and so is the amount of filler material required for follow-up injections. Conclusion: Facial contour remodelling is being revolutionised by the new filler materials for volume augmentation and no uniform consensus has been reached on the techniques currently used in clinical practice. We advocate this novel PPT technique of facial filling in facial rejuvenation to restore a youthful look as a primary goal. PMID:24987203

  8. Hyaluronic acid-N-hydroxysuccinimide: a useful intermediate for bioconjugation.

    PubMed

    Luo, Y; Prestwich, G D

    2001-01-01

    Hyaluronic acid (HA) is an abundant nonsulfated glycosaminoglycan component of synovial fluid and the extracellular matrix. HA is an important building block for biocompatible and biointeractive materials with applications in drug delivery, tissue engineering, wound repair, and viscosupplementation. Herein we describe the synthesis and characterization of HA-N-succinimide, an activated ester of the glucuronic acid moiety. This HA-active ester intermediate is a precursor for fluorescent probes, drug-polymer conjugates, and cross-linked hydrogels. As a demonstration, we used HA-NHS to prepare HA-BODIPY by coupling with the hydrazide derivative of the fluor. Intracellular uptake of HA-BODIPY into human ovarian cancer cells, which overexpress cell-surface HA receptors, was visualized using confocal microscopy. PMID:11716704

  9. 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. PMID:19810117

  10. 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. PMID:24845645

  11. STYLAGE®: a range of hyaluronic acid dermal fillers containing mannitol. Physical properties and review of the literature

    PubMed Central

    Ramos-e-Silva, Marcia; Fonteles, Lívia Arcanjo; Lagalhard, Cecília Schubert Xavier; Fucci-da-Costa, Ana Paula Cercal

    2013-01-01

    Dermatological procedures which are considered as being minimally invasive, such as those using injectable fillers based on hyaluronic acid, revolutionized aging treatment, especially of the face. By promoting the replacement of lost volume and attenuating grooves and wrinkles, they ensure a more youthful appearance and certain functional recovery of facial aesthetics. The authors review some of the main physicochemical characteristics of these dermal fillers, highlighting the product line Stylage®, the manufacture of which includes mannitol. PMID:24187508

  12. Fabrication of Biopolymer Nanofibers of Hyaluronic Acid via Electrospinning

    NASA Astrophysics Data System (ADS)

    Young, Denice; Queen, Hailey; Krause, Wendy

    2006-03-01

    Electrospinning is a novel technology that uses an electric field to form fibrous materials from a polymer solution. Unlike traditional spinning techniques, electrospinning can produce fibers on the order of 100 nm that can be utilized in applications where nanoscale fibers are necessary for successful implementation, including tissue engineering. Hyaluronic acid (HA) is a widely used biopolymer found in the extracellular matrix and currently marketed in medical applications for joint lubrications and tissue engineering. The high viscosity and surface tension of HA make it an unlikely candidate for electrospinning processes as viscosity is an important parameter in successful electrospinning. To promote HA fiber formation by electrospinning, the effects of salt (NaCl), which is used to reduce the viscosity of aqueous HA solutions; molecular weight of the HA; and an additional biocompatible polymer (e.g., PEO) are under investigation.

  13. Hyaluronic acid: A key molecule in skin aging

    PubMed Central

    Papakonstantinou, Eleni; Roth, Michael; Karakiulakis, George

    2012-01-01

    Skin aging is a multifactorial process consisting of two distinct and independent mechanisms: intrinsic and extrinsic aging. Youthful skin retains its turgor, resilience and pliability, among others, due to its high content of water. Daily external injury, in addition to the normal process of aging, causes loss of moisture. The key molecule involved in skin moisture is hyaluronic acid (HA) that has unique capacity in retaining water. There are multiple sites for the control of HA synthesis, deposition, cell and protein association and degradation, reflecting the complexity of HA metabolism. The enzymes that synthesize or catabolize HA and HA receptors responsible for many of the functions of HA are all multigene families with distinct patterns of tissue expression. Understanding the metabolism of HA in the different layers of the skin and the interactions of HA with other skin components will facilitate the ability to modulate skin moisture in a rational manner. PMID:23467280

  14. Acetylated Hyaluronic Acid: Enhanced Bioavailability and Biological Studies

    PubMed Central

    Saturnino, Carmela; Sinicropi, Maria Stefania; Puoci, Francesco

    2014-01-01

    Hyaluronic acid (HA), a macropolysaccharidic component of the extracellular matrix, is common to most species and it is found in many sites of the human body, including skin and soft tissue. Not only does HA play a variety of roles in physiologic and in pathologic events, but it also has been extensively employed in cosmetic and skin-care products as drug delivery agent or for several biomedical applications. The most important limitations of HA are due to its short half-life and quick degradation in vivo and its consequently poor bioavailability. In the aim to overcome these difficulties, HA is generally subjected to several chemical changes. In this paper we obtained an acetylated form of HA with increased bioavailability with respect to the HA free form. Furthermore, an improved radical scavenging and anti-inflammatory activity has been evidenced, respectively, on ABTS radical cation and murine monocyte/macrophage cell lines (J774.A1). PMID:25114930

  15. 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. PMID:26944660

  16. Electrical conduction in macroscopically oriented deoxyribonucleic and hyaluronic acid samples

    NASA Astrophysics Data System (ADS)

    Kutnjak, Zdravko; Lahajnar, Gojmir; Filipič, Cene; Podgornik, Rudolf; Nordenskiöld, Lars; Korolev, Nikolay; Rupprecht, Allan

    2005-04-01

    Measurements of the quasistatic and frequency dependent electrical conductivity below 1 MHz were carried out on wet-spun, macroscopically oriented, calf thymus deoxyribonucleic (DNA) and umbilical cord hyaluronic acid (HA) bulk samples. The frequency dependence of the electrical conductivity in the frequency range of approximately 10-3-106Hz of both materials is surprisingly rather similar. Temperature dependence of the quasistatic electrical conductivity above the low temperature saturation plateau can be well described by the activated Arrhenius law with the activation energy of ≈0.8eV for both DNA and HA. We discuss the meaning of these findings for the possible conduction mechanism in these particular charged polyelectrolytes.

  17. Perpendicular Strut Injection of Hyaluronic Acid Filler for Deep Wrinkles

    PubMed Central

    Mashiko, Takanobu; Kinoshita, Kahori; Kanayama, Koji; Feng, Jingwei

    2015-01-01

    Summary: Although various injection techniques of hyaluronic acid (HA) filler for facial rejuvenation have been developed, correction of deep wrinkles/grooves, such as the nasolabial fold (NLF), with intradermal or subdermal injections remains difficult. We tested the intradermal HA injection method to place multiple HA struts by (1) inserting a small needle perpendicularly to the wrinkle and (2) injecting HA as intradermal struts with the skin fully stretched by the practitioner’s fingers. The results of both NLFs in 10 patients suggest that this technique improves NLFs and maintain the effects more consistently than conventional techniques, although the effects of both methods were almost lost after 6 months. Selective and/or combined application of this technique may enhance the current approach to facial rejuvenation with dermal fillers. PMID:26893992

  18. Perpendicular Strut Injection of Hyaluronic Acid Filler for Deep Wrinkles.

    PubMed

    Mashiko, Takanobu; Kinoshita, Kahori; Kanayama, Koji; Feng, Jingwei; Yoshimura, Kotaro

    2015-11-01

    Although various injection techniques of hyaluronic acid (HA) filler for facial rejuvenation have been developed, correction of deep wrinkles/grooves, such as the nasolabial fold (NLF), with intradermal or subdermal injections remains difficult. We tested the intradermal HA injection method to place multiple HA struts by (1) inserting a small needle perpendicularly to the wrinkle and (2) injecting HA as intradermal struts with the skin fully stretched by the practitioner's fingers. The results of both NLFs in 10 patients suggest that this technique improves NLFs and maintain the effects more consistently than conventional techniques, although the effects of both methods were almost lost after 6 months. Selective and/or combined application of this technique may enhance the current approach to facial rejuvenation with dermal fillers. PMID:26893992

  19. 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. PMID:23088321

  20. Recent advances in hyaluronic acid hydrogels for biomedical applications.

    PubMed

    Highley, Christopher B; Prestwich, Glenn D; Burdick, Jason A

    2016-08-01

    Hyaluronic acid (HA) is widely used in the design of engineered hydrogels, due to its biofunctionality, as well as numerous sites for modification with reactive groups. There are now widespread examples of modified HA macromers that form either covalent or physical hydrogels through crosslinking reactions such as with click chemistry or supramolecular assemblies of guest-host pairs. HA hydrogels range from relatively static matrices to those that exhibit spatiotemporally dynamic properties through external triggers like light. Such hydrogels are being explored for the culture of cells in vitro, as carriers for cells in vivo, or to deliver therapeutics, including in an environmentally responsive manner. The future will bring new examples of HA hydrogels due to the synthetic diversity of HA. PMID:26930175

  1. 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

  2. Cell-free cartilage engineering approach using hyaluronic acid-polycaprolactone scaffolds: a study in vivo.

    PubMed

    Lebourg, M; Martínez-Díaz, S; García-Giralt, N; Torres-Claramunt, R; Gómez-Tejedor, J A; Ribelles, J L Gómez; Vila-Canet, G; Monllau, J C

    2014-05-01

    Polycaprolactone scaffolds modified with cross-linked hyaluronic acid were prepared in order to establish whether a more hydrophilic and biomimetic microenvironment benefits the progenitor cells arriving from bone marrow in a cell-free tissue-engineering approach. The polycaprolactone and polycaprolactone/hyaluronic acid scaffolds were characterized in terms of morphology and water absorption capacity. The polycaprolactone and polycaprolactone/hyaluronic acid samples were implanted in a chondral defect in rabbits; bleeding of the subchondral bone was provoked to generate a spontaneous healing response. Repair at 1, 4, 12, and 24 weeks was assessed macroscopically using the International Cartilage Repair Society score and the Oswestry Arthroscopy Score and microscopically using immunohistological staining for collagen type I and type II, and for Ki-67. The presence of hyaluronic acid improves scaffold performance, which supports a good repair response without biomaterial pre-seeding. PMID:24108064

  3. 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. PMID:25447786

  4. A Novel Technique of Supra Superficial Musculoaponeurotic System Hyaluronic Acid Injection for Lower Face Lifting

    PubMed Central

    Sahawatwong, Sinijchaya; Sirithanabadeekul, Punyaphat; Patanajareet, Vasiyapha; Wattanakrai, Penpun

    2016-01-01

    Background: Various methods attempting to correct sagging of the lower face focus mainly on manipulation of the superficial musculoaponeurotic System. Each technique has its own limitation. The authors propose a relatively simple, conservative method utilizing hyaluronic acid injection just above the superficial musculoaponeurotic System. Objective: To address a novel hyaluronic injection technique to lift the lower face. Methods: Details of the injection techniques are described. The Position of the hyaluronic acid injected and the effect of hyaluronic acid on the superficial musculoaponeurotic System were confirmed by ultrasonography in one of the cases. Results: Sonogram images demonstrated the location of the injected hyaluronic acid and pressure effect of hyaluronic acid on the superficial musculoaponeurotic System, confirming the ability to manipulate the superficial musculoaponeurotic System by this injection technique. The lifting result of this Single injection technique was immediately visible and maintained for at least 26 weeks. Conclusion: This is a less invasive, reproducible method that provides a sustained face lifting result. The authors propose the term “supraSMAS lift” for this novel injection technique. PMID:27047633

  5. The effects of hyaluronic acid incorporated as a wetting agent on lysozyme denaturation in model contact lens materials.

    PubMed

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

    2013-09-01

    Conventional and silicone hydrogels as models for contact lenses were prepared to determine the effect of the presence of hyaluronic acid on lysozyme sorption and denaturation. Hyaluronic acid was loaded into poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/TRIS--methacryloxypropyltris (trimethylsiloxy silane) hydrogels, which served as models for conventional and silicone hydrogel contact lens materials. The hyaluronic acid was cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide in the presence of dendrimers. Active lysozyme was quantified using a Micrococcus lysodeikticus assay while total lysozyme was determined using 125-I radiolabeled protein. To examine the location of hyaluronic acid in the gels, 6-aminofluorescein labeled hyaluronic acid was incorporated into the gels using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry and the gels were examined using confocal laser scanning microscopy. Hyaluronic acid incorporation significantly reduced lysozyme sorption in poly(2-hydroxyethyl methacrylate) (p < 0.00001) and poly(2-hydroxyethyl methacrylate)/TRIS--methacryloxypropyltris (trimethylsiloxy silane) (p < 0.001) hydrogels, with the modified materials sorbing only 20% and 16% that of the control, respectively. More importantly, hyaluronic acid also decreased lysozyme denaturation in poly(2-hydroxyethyl methacrylate) (p < 0.005) and poly(2-hydroxyethyl methacrylate)/TRIS--methacryloxypropyltris (trimethylsiloxy silane) (p < 0.02) hydrogels. The confocal laser scanning microscopy results showed that the hyaluronic acid distribution was dependent on both the material type and the molecular weight of hyaluronic acid. This study demonstrates that hyaluronic acid incorporated as a wetting agent has the potential to reduce lysozyme sorption and denaturation in contact lens applications. The distribution of hyaluronic acid within hydrogels appears to affect denaturation, with more surface mobile, lower

  6. 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),…

  7. Enzymatically cross-linked alginic-hyaluronic acid composite hydrogels as cell delivery vehicles.

    PubMed

    Ganesh, Nitya; Hanna, Craig; Nair, Shantikumar V; Nair, Lakshmi S

    2013-04-01

    An injectable composite gel was developed from alginic and hyaluronic acid. The enzymatically cross-linked injectable gels were prepared via the oxidative coupling of tyramine modified sodium algiante and sodium hyaluronate in the presence of horse radish peroxidase (HRP) and hydrogen peroxide (H2O2). The composite gels were prepared by mixing equal parts of the two tyraminated polymer solutions in 10U HRP and treating with 1.0% H2O2. The properties of the alginate gels were significantly affected by the addition of hyaluronic acid. The percentage water absorption and storage modulus of the composite gels were found to be lower than the alginate gels. The alginate and composite gels showed lower protein release compared to hyaluronate gels in the absence of hyaluronidase. Even hyaluronate gels showed only approximately 10% protein release after 14 days incubation in phosphate buffer solution. ATDC-5 cells encapsulated in the injectable gels showed high cell viability. The composite gels showed the presence of enlarged spherical cells with significantly higher metabolic activity compared to cells in hyaluronic and alginic acid gels. The results suggest the potential of the composite approach to develop covalently cross-linked hydrogels with tuneable physical, mechanical, and biological properties. PMID:23357799

  8. Hyaluronic Acid Based Hydrogels for Regenerative Medicine Applications.

    PubMed

    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

  9. Association between cationic liposomes and low molecular weight hyaluronic acid.

    PubMed

    Gasperini, Antonio A M; Puentes-Martinez, Ximena E; Balbino, Tiago Albertini; Rigoletto, Thais de Paula; Corrêa, Gabriela de Sá Cavalcanti; Cassago, Alexandre; Portugal, Rodrigo Villares; de La Torre, Lucimara Gaziola; Cavalcanti, Leide P

    2015-03-24

    This work presents a study of the association between low molecular weight hyaluronic acid (16 kDa HA) and cationic liposomes composed of egg phosphatidylcholine (EPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The cationic liposome/HA complexes were evaluated to determine their mesoscopic structure, average size, zeta potential, and morphology as a function of the amount of HA in the system. Small angle X-ray scattering results revealed that neighboring cationic liposomes either stick together after a partial coating of low concentration HA or disperse completely in excess of HA, but they never assemble as multilamellar vesicles. Cryo-transmission electron microscopy images confirm the existence of unilamellar vesicles and large aggregates of unilamellar vesicles for HA fractions up to 80% (w/w). High concentrations of HA (> 20% w/w) proved to be efficient for coating extruded liposomes, leading to particle complexes with sizes in the nanoscale range and a negative zeta potential. PMID:25730494

  10. 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. PMID:24614580

  11. A new drug nanocarrier consisting of polyarginine and hyaluronic acid.

    PubMed

    Oyarzun-Ampuero, Felipe A; Goycoolea, Francisco M; Torres, Dolores; Alonso, Maria J

    2011-09-01

    The purpose of this study was to produce and characterize a variety of nanostructures comprised of the polyaminoacid polyarginine (PArg) and the polysaccharide hyaluronic acid (HA) as a preliminary stage before evaluating their potential application in drug delivery. PArg was combined with high- or low-molecular-weight HA (HMWHA or LMWHA, respectively) to form nanoparticles by simply mixing polymeric aqueous solutions at room temperature. The average size of the resulting nanocarriers was between 116 and 155 nm, and their zeta potential value ranged from +31.3 to -35.9 mV, indicating that the surface composition of the particle could be conveniently modified according to the mass ratio of the polymers. Importantly, the systems prepared with HMWHA remained stable after isolation by centrifugation and in conditions that mimic the physiological medium, whereas particles that incorporated LMWHA were unstable. Transmission electron microscopy showed that the nanostructures made with HMWHA were spherical. Finally, the systems were stable for at least three months at storage conditions (4°C). PMID:21549838

  12. Bioinspired lubricating films of cellulose nanofibrils and hyaluronic acid.

    PubMed

    Valle-Delgado, Juan José; Johansson, Leena-Sisko; Österberg, Monika

    2016-02-01

    The development of materials that combine the excellent mechanical strength of cellulose nanofibrils (CNF) with the lubricating properties of hyaluronic acid (HA) is a new, promising approach to cartilage implants not explored so far. A simple, solvent-free method to produce a very lubricating, strong cellulosic material by covalently attaching HA to the surface of CNF films is described in this work. A detailed analysis of the tribological properties of the CNF films with and without HA is also presented. Surface and friction forces at micro/nanoscale between model hard surfaces (glass microspheres) and the CNF thin films were measured using an atomic force microscope and the colloid probe technique. The effect of HA attachment, the pH and the ionic strength of the aqueous medium on the forces was examined. Excellent lubrication was observed for CNF films with HA attached in conditions where the HA layer was highly hydrated. These results pave the way for the development of new nanocellulose-based materials with good lubrication properties that could be used in biomedical applications. PMID:26674836

  13. Collagen-hyaluronic acid scaffolds for adipose tissue engineering.

    PubMed

    Davidenko, N; Campbell, J J; Thian, E S; Watson, C J; Cameron, R E

    2010-10-01

    Three-dimensional (3-D) in vitro models of the mammary gland require a scaffold matrix that supports the development of adipose stroma within a robust freely permeable matrix. 3-D porous collagen-hyaluronic acid (HA: 7.5% and 15%) scaffolds were produced by controlled freeze-drying technique and crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride. All scaffolds displayed uniform, interconnected pore structure (total porosity approximately 85%). Physical and chemical analysis showed no signs of collagen denaturation during the formation process. The values of thermal characteristics indicated that crosslinking occurred and that its efficiency was enhanced by the presence of HA. Although the crosslinking reduced the swelling of the strut material in water, the collagen-HA matrix as a whole tended to swell more and show higher dissolution resistance than pure collagen samples. The compressive modulus and elastic collapse stress were higher for collagen-HA composites. All the scaffolds were shown to support the proliferation and differentiation 3T3-L1 preadipocytes while collagen-HA samples maintained a significantly increased proportion of cycling cells (Ki-67+). Furthermore, collagen-HA composites displayed significantly raised Adipsin gene expression with adipogenic culture supplementation for 8 days vs. control conditions. These results indicate that collagen-HA scaffolds may offer robust, freely permeable 3-D matrices that enhance mammary stromal tissue development in vitro. PMID:20466086

  14. 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

  15. 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

  16. Synthesis and characterization of hybrid hyaluronic acid-gelatin hydrogels.

    PubMed

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

    2013-04-01

    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 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. Localization of hyaluronic acid in human articular cartilage.

    PubMed

    Asari, A; Miyauchi, S; Kuriyama, S; Machida, A; Kohno, K; Uchiyama, Y

    1994-04-01

    To demonstrate localization of hyaluronic acid (HA) in articular cartilage of the human femur, biotinylated HA-binding region, which specifically binds HA molecules, was applied to the tissue. In sections fixed by 2% paraformaldehyde-2% glutaraldehyde, HA staining was detected in lamina splendens and chondrocytes in the middle zone. By pretreatment with trypsin, intense HA staining appeared in the extracellular matrix of the deep zone and weak staining in the superficial and middle zones. Moreover, pre-treatment with chondroitinase ABC (CHase ABC) intensely enhanced the stainability for HA in the superficial and middle zones and weakly in the deeper zone. Combined pre-treatment of trypsin with CHase ABC abolished intra- and extracellular staining for HA in all zones. By microbiochemical study, the concentrations of HA and dermatan sulfate were high in the middle zone, whereas those of chondroitin sulfate and keratan sulfate were high in the deep zone. These results suggest that HA is abundantly synthesized in and secreted from the chondrocytes, particularly in the middle zone, whereas it is largely masked by proteoglycan constituents in the extracellular matrix. PMID:8126377

  18. 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

  19. Functional hyaluronic acid hydrogels prepared by a novel method.

    PubMed

    Cui, Ning; Qian, Junmin; Zhao, Na; Wang, Hongjie

    2014-12-01

    In this study, a novel simple method was developed to prepare functional hyaluronic acid (HA) hydrogels simultaneously containing hydrazone and disulfide bonds in their crossbridges. The HA hydrogels were formed by directly reacting 2,5-hexanedione and 3,3'-dithiodipropionate hydrazide-modified HA, and were characterized by FT-IR, SEM, TGA and mechanical tests. The results showed that the formation of HA hydrogels was a result of the reaction between ketone and hydrazide groups. The resultant HA hydrogels exhibited a porous morphology with a pore size range of 50 μm to 400 μm, and their compressive modulus and G″/G' ratio were 18.8±0.6 kPa and 0.002, respectively. Both swelling and degradation ratios gradually decreased with the increasing degree of crosslinking. However, the degree of crosslinking had a slight effect on the decomposition temperature of the HA hydrogels. It can be concluded that the simple method presented in this study is feasible to prepare HA hydrogels through hydrazone bond crosslinking by reacting diketone molecules and hydrazide-modified HA, and the HA hydrogels have potential in biomedical applications. PMID:25491866

  20. Efficient in vivo gene transfection by stable DNA/PEI complexes coated by hyaluronic acid.

    PubMed

    Ito, Tomoko; Iida-Tanaka, Naoko; Koyama, Yoshiyuki

    2008-05-01

    Plasmid DNA was mixed with polyethyleneimine (PEI) and hyaluronic acid (HA) to afford ternary complexes with negative surface charge regardless of the mixing order. They showed reduced non-specific interactions with blood components. When DNA and PEI were mixed at a high concentration such as that used in in vivo experiments, they soon aggregated, and large particles were formed. On the other hand, pre-addition of HA to DNA prior to PEI effectively diminished the aggregation, and 10% (in volume) of the complexes remained as small particles with a diameter below 80 nm. Those negatively charged small ternary complexes induced a much stronger extra-gene expression in tumor than binary DNA/PEI complex after intratumoral or intravenous injection into the mice bearing B16 cells. PMID:18446606

  1. 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. PMID:26967521

  2. A clinical study to assess the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation

    PubMed Central

    Littara, A; Palmieri, B; Rottigni, V; Iannitti, T

    2013-01-01

    Premature ejaculation is a sexual debilitating condition affecting a large number of men worldwide and leading to important dysfunctions influencing the patients' affective and emotional life. Hyaluronic acid is a natural and safe compound that has been widely used not only in the aesthetic medicine clinic, but also for treatment of osteoarthritis. The present study shows the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation. A hundred and ten male patients were treated with hyaluronic acid injections in the deep dermis of their glans penis to increase the volume and the circumference of their penis to prevent male premature ejaculation and improve the patients' and their partners' sexual satisfaction. The intravaginal ejaculation latency time increased significantly from a baseline value of 88.34±3.14 s to 293.14±8.16 s after 6 months from the procedure. Maximal glandular circumference increased from 98.51±0.71 mm to 114.35±0.66 mm after 6 months from the procedure. At 6-month follow-up, patients' self-rated satisfaction was 5.3±0.07 (range: 4–6). At the follow-up, partners' self-rated satisfaction was 5.1±0.09 (range: 3–6). The present clinical study showed that hyaluronic acid injection is a promising treatment for premature ejaculation. The effect of the procedure in the long-term follow-up needs to be clarified. PMID:23552577

  3. A clinical study to assess the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation.

    PubMed

    Littara, A; Palmieri, B; Rottigni, V; Iannitti, T

    2013-05-01

    Premature ejaculation is a sexual debilitating condition affecting a large number of men worldwide and leading to important dysfunctions influencing the patients' affective and emotional life. Hyaluronic acid is a natural and safe compound that has been widely used not only in the aesthetic medicine clinic, but also for treatment of osteoarthritis. The present study shows the effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation. A hundred and ten male patients were treated with hyaluronic acid injections in the deep dermis of their glans penis to increase the volume and the circumference of their penis to prevent male premature ejaculation and improve the patients' and their partners' sexual satisfaction. The intravaginal ejaculation latency time increased significantly from a baseline value of 88.34±3.14 s to 293.14±8.16 s after 6 months from the procedure. Maximal glandular circumference increased from 98.51±0.71 mm to 114.35±0.66 mm after 6 months from the procedure. At 6-month follow-up, patients' self-rated satisfaction was 5.3±0.07 (range: 4-6). At the follow-up, partners' self-rated satisfaction was 5.1±0.09 (range: 3-6). The present clinical study showed that hyaluronic acid injection is a promising treatment for premature ejaculation. The effect of the procedure in the long-term follow-up needs to be clarified. PMID:23552577

  4. Optimizing facial rejuvenation outcomes by combining poly-L-lactic acid, hyaluronic acid, calcium hydroxylapatite, and neurotoxins: two case studies.

    PubMed

    Lorenc, Z Paul; Daro-Kaftan, Elizabeth

    2014-02-01

    Reversal of the visible signs of facial aging with the use of injectable products as an alternative to surgery has become more popular, with nearly 5 million procedures performed in the United States in 2012. Volume augmentation products, such as hyaluronic acid (HA), calcium hydroxylapatite (CaHA), and poly-L-lactic acid (PLLA), are often used in combination with one another and with neurotoxins for facial rejuvenation because of the complementary modes of action. This article presents 2 case reports involving patientspecific combinations of 2 different HA products, injectable PLLA, and CaHA with incobotulinumtoxinA or abobotulinumtoxinA. The combination of HA, CaHA, PLLA, and neurotoxins has resulted in outstanding outcomes for many patients, with no clinical evidence of increased adverse events secondary to combination therapy. PMID:24509971

  5. Effect of hyaluronic acids as chondroprotective in experimental model of osteoarthrosis☆☆☆

    PubMed Central

    Oliveira, Marcello Zaia; Albano, Mauro Batista; Namba, Mario Massatomo; da Cunha, Luiz Antônio Munhoz; de Lima Gonçalves, Renan Rodrigues; Trindade, Edvaldo Silva; Andrade, Lucas Ferrari; Vidigal, Leandro

    2014-01-01

    Objective to analyze the effects of hyaluronic acid of different molecular weights in an experimental model of osteoarthritis in rabbits. Methods forty‐four male California rabbits were divided randomly into three groups and underwent resection of the anterior cruciate ligament in his right knee. After three weeks of the surgical procedure began three weekly intra‐articular injections of hyaluronic acid native (Polireumin®)‐PR, hyaluronic acid branched chain (Synvisc®)‐S and 0.9% saline‐P. All animals were sacrificed after twelve weeks of surgery and tibial plateau infiltrated the knees were dissected. Histological cartilage of the support areas of the tibial plateaus were stained with Alcian Blue pH 1.0, Alcian Blue pH = 2.5 and toluidine blue for research on the amount of proteoglycans. The intensity of staining was quantified on a Zeiss microscope apparatus Imager Z2 MetaSystems and analyzed by software MetaferMsearch. Results the effect of chondroprotetor hyaluronic acids used in the study was confirmed when compared to the control group, but the comparison made between them, there was no statistically significant difference regarding chondroprotetion. Conclusion the hyaluronic acids tested had chondroprotective effect, with no statistical difference with regard to the different molecular weights. PMID:26229774

  6. Hyaluronic acid as a molecular filter and friction-reducing lubricant in the human inner ear.

    PubMed

    Anniko, M; Arnold, W

    1995-01-01

    Immunofluorescence for hyaluronic acid occurred intracellularly in morphologically highly specialized areas in the adult human inner ear, for instance in the cuticular plates of all types of hair cells, at the apposition between outer hair cells and Deiter's cell bodies and in the near-surface area of Hensen's cells. The cytoskeletal organization in these regions is characterized by tightly packed filamentous proteins. Under physiological stimulus these regions undergo micromechanical change, either actively moving (force generation) or passively vibrating with changes in elasticity. Hyaluronic acid might therefore act as a friction-reducing molecular lubricant. In the lateral wall of the cochlea an accumulation of hyaluronic acid occurred in the loose connective tissue of the spiral ligament, in particular close to the stria vascularis. Due to its complex molecular network, hyaluronic acid offers considerable resistance to bulk flow of water and may exclude molecules. The basal cell region of the stria vascularis is thus given additional support to minimize (seal?) the stria vascularis towards all other areas except the endolymphatic space. Here, hyaluronic acid could act as a molecular filter. PMID:7731661

  7. Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering.

    PubMed

    Tan, Huaping; Ramirez, Christina M; Miljkovic, Natasa; Li, Han; Rubin, J Peter; Marra, Kacey G

    2009-12-01

    A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4'-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by (1)H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as approximately 30 degrees C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37 degrees C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37 degrees C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications. PMID:19783043

  8. Synthesis and degradation test of hyaluronic acid hydrogels.

    PubMed

    Hahn, Sei Kwang; Park, Jung Kyu; Tomimatsu, Takashi; Shimoboji, Tsuyoshi

    2007-03-10

    Hyaluronic acid (HA) hydrogels prepared with three different crosslinking reagents were assessed by in vitro and in vivo degradation tests for various tissue engineering applications. Adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and used for the preparation of methacrylated HA (HA-MA) with methacrylic anhydride and thiolated HA (HA-SH) with Traut's reagent (imminothiolane). (1)H NMR analysis showed that the degrees of HA-ADH, HA-MA, and HA-SH modification were 69, 29, and 56 mol%, respectively. HA-ADH hydrogel was prepared by the crosslinking with bis(sulfosuccinimidyl) suberate (BS(3)), HA-MA hydrogel with dithiothreitol (DTT) by Michael addition, and HA-SH hydrogel with sodium tetrathionate by disulfide bond formation. According to in vitro degradation tests, HA-SH hydrogel was degraded very fast, compared to HA-ADH and HA-MA hydrogels. HA-ADH hydrogel was degraded slightly faster than HA-MA hydrogel. Based on these results, HA-MA hydrogels and HA-SH hydrogels were implanted in the back of SD rats and their degradation was assessed according to the pre-determined time schedule. As expected from the in vitro degradation test results, HA-SH hydrogel was in vivo degraded completely only in 2 weeks, whereas HA-MA hydrogels were degraded only partially even in 29 days. The degradation rate of HA hydrogels were thought to be controlled by changing the crosslinking reagents and the functional group of HA derivatives. In addition, the state of HA hydrogel was another factor in controlling the degradation rate. Dried HA hydrogel at 37 degrees C for a day resulted in relatively slow degradation compared to the bulk HA hydrogel. There was no adverse effect during the in vivo tests. PMID:17101173

  9. Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering

    PubMed Central

    Tan, Huaping; Ramirez, Christina M.; Miljkovic, Natasa; Li, Han; Rubin, J. Peter; Marra, Kacey G.

    2009-01-01

    A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4′-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by 1H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as ~30°C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37°C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37°C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications. PMID:19783043

  10. The radiation-induced degradation of hyaluronic acid

    NASA Astrophysics Data System (ADS)

    Deeble, D. J.; Phillips, G. O.; Bothe, E.; Schuchmann, H.-P.; von Sonntag, C.

    Free-radical-induced chain scission in hyaluronic acid in aqueous solution has been studied using pulse radiolysis. In the absence of oxygen (nitrous oxide-saturated solutions) the process of chain breakage was monitored by measuring changes in conductivity resulting from the release of condensed counter-ions (K +), originally located in the vicinity of the break. The rate of formation of breaks was found to be first order and was catalysed by acid and base (overall half-lives at pH values of 4.8, 7 and 10.2 were 0.6, 1 and 0.1 ms). It would seem that more than two independent reaction pathways are involved in the cleavage processes. In the presence of oxygen (N 2O/O 2), chain scission has been measured by pulse radiolysis monitoring changes in scattered light intensity as well as following conductivity changes. In oxygenated solutions, the kinetics of OH-radical-induced chain scission were found to contain a second-order component; the rate of breakage was base catalysed. Yield-dose plots for chain breaks (N 2O/O 2, pulse-irradiated), showed a marked dependence on pH, with G-values (molecules/100 eV) of 0.7, 2.5 and 4.7 at pH values of 7, 9.7 and 10.4, respectively. Steady-state radiolysis (N 2O/O 2) was used to determine G-values for oxygen consumption [ G(-O 2) ≈ 6], carbon dioxide formation [ G(CO 2) = 0.8 in the absence of O 2 and 1.3 in its presence] and peroxide formation [ G(H 2O 2) ≈ 2; G(organic hydroperoxide) < 0.15].

  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. Effect of Hyaluronic Acid Incorporation Method on the Stability and Biological Properties of Polyurethane-Hyaluronic Acid Biomaterials

    PubMed Central

    Ruiz, Amaliris; Rathnam, Kashmila R.; Masters, Kristyn S.

    2014-01-01

    The high failure rate of small diameter vascular grafts continues to drive the development of new materials and modification strategies that address this clinical problem, with biomolecule incorporation typically achieved via surface-based modification of various biomaterials. In this work, we examined whether the method of biomolecule incorporation (i.e., bulk vs. surface modification) into a polyurethane (PU) polymer impacted biomaterial performance in the context of vascular applications. Specifically, hyaluronic acid (HA) was incorporated into a poly(ether urethane) via bulk copolymerization or covalent surface tethering, and the resulting PU-HA materials characterized with respect to both physical and biological properties. Modification of PU with HA by either surface or bulk methods yielded materials that, when tested under static conditions, possessed no significant differences in their ability to resist protein adsorption, platelet adhesion, and bacterial adhesion, while supporting endothelial cell culture. However, only bulk-modified PU-HA materials were able to fully retain these characteristics following material exposure to flow, demonstrating a superior ability to retain the incorporated HA and minimize enzymatic degradation, protein adsorption, platelet adhesion, and bacterial adhesion. Thus, despite bulk methods rarely being implemented in the context of biomolecule attachment, these results demonstrate improved performance of PU-HA upon bulk, rather than surface, incorporation of HA. Although explored only in the context of PU-HA, the findings revealed by these experiments have broader implications for the design and evaluation of vascular graft modification strategies. PMID:24276670

  13. The Use of Hyaluronic Acid after Tendon Surgery and in Tendinopathies

    PubMed Central

    Schiavone, Cosima; Salini, Vincenzo

    2014-01-01

    Viscosupplementation with hyaluronic acid is safe and effective in the management of osteoarthritis, but its use in the treatment of tendon disorders has received less attention. The aim of this review is to summarize the current knowledge on this topic, evaluating experimental and clinical trials. A search of English-language articles was performed using the key search terms “hyaluronic acid” or “viscosupplementation” combined with “tendon,” “tendinopathy,“ “adhesions,“ or “gliding,“ independently. In quite all the experimental studies, performed after surgical procedures for tendon injuries or in the treatment of chronic tendinopathies, using different hyaluronic acid compounds, positive results (reduced formation of scars and granulation tissue after tendon repair, less adhesions and gliding resistance, and improved tissue healing) were observed. In a limited number of cases, hyaluronic acid has been employed in clinical practice. After flexor tendon surgery, a greater total active motion and fingers function, with an earlier return to work and daily activities, were observed. Similarly, in patients suffering from elbow, patellar, and shoulder tendons disorders, pain was reduced, and function improved. The positive effect of hyaluronic acid can be attributed to the anti-inflammatory activity, enhanced cell proliferation, and collagen deposition, besides the lubricating action on the sliding surface of the tendon. PMID:24895610

  14. 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

  15. 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

  16. 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. PMID:25110287

  17. Reducing protein adsorption with polymer-grafted hyaluronic acid coatings.

    PubMed

    Ramadan, Mohamed H; Prata, Joseph E; Karácsony, Orsolya; Dunér, Gunnar; Washburn, Newell R

    2014-07-01

    We report a thermoresponsive chemical modification strategy of hyaluronic acid (HA) for coating onto a broad range of biomaterials without relying on chemical functionalization of the surface. Poly(di(ethylene glycol) methyl ether methacrylate) (PMEO2MA), a polymer with a lower critical solution temperature of 26 °C in water, was grafted onto HA to allow facile formation of biopolymer coatings. While the mechanism for film formation appears to involve a complex combination of homogeneous nucleation followed by heterogeneous film growth, we demonstrate that it resulted in hydrophilic coatings that significantly reduce protein adsorption despite the high fraction of hydrophobic (PMEO2MA). Structural characterization was performed using atomic force microscopy (AFM), which showed the formation of a dense, continuous coating based on 200 nm domains that were stable in protein solutions for at least 15 days. The coatings had a water contact angle of 16°, suggesting the formation of hydrophilic but not fully wetting films. Quartz crystal microbalance with dissipation monitoring (QCM-D) as well as biolayer interferometry (BLI) techniques were used to measure adsorption of bovine serum albumin (BSA), fibrinogen (Fbg), and human immunoglobulin (IgG), with results indicating that HA-PMEO2MA-coated surfaces effectively inhibited adsorption of all three serum proteins. These results are consistent with previous studies demonstrating that this degree of hydrophilicity is sufficient to generate an effectively nonfouling surface and suggest that segregation during the solubility transition resulted in a surface that presented the hydrophilic HA component of the hybrid biopolymer. We conclude that PMEO2MA-grafted HA is a versatile platform for the passivation of hydrophobic biomaterial surfaces without need for substrate functionalization. PMID:24892924

  18. Anti-inflammatory drug delivery from hyaluronic acid hydrogels.

    PubMed

    Hahn, Sei K; Jelacic, Sandra; Maier, Ronald V; Stayton, Patrick S; Hoffman, Allan S

    2004-01-01

    Two different types of hyaluronic acid (HA) hydrogels were synthesized by crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were loaded into the gels and their release kinetics were measured in vitro. VES and BSA released with a burst from both HA hydrogels during the first few hours, and release continued gradually for several days. The rate of release from HA-VS-PEG-VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to the lower crosslink density in the former. The anti-inflammatory action of released VES was tested by incubating peripheral blood mononuclear cells (PBMC) on HA hydrogels with and without VES in the gel. The number of cells adhering on HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS), which might be one of the important advantages of using HA hydrogels for implant coatings or tissue engineering applications. ELISA test results showed that the tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the supernatant of the wells containing the HA hydrogel with VES in contact with the activated macrophages compared to that without VES. This is probably the effect of the released VES reducing the production of anti-inflammatory cytokine, TNF-alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use in tissue engineering and also as biocompatible coatings of implants. PMID:15503629

  19. A new viscosupplement based on partially hydrophobic hyaluronic acid: a comparative study.

    PubMed

    Finelli, Ivana; Chiessi, Ester; Galesso, Devis; Renier, Davide; Paradossi, Gaio

    2011-01-01

    A novel partially hydrophobized derivative of hyaluronic acid (HYADD® 4), containing a low number of C16 side-chains per polysaccharide backbone, provides injectable hydrogels stabilized by side-chain hydrophobic interactions. The rheological properties of Hymovis®, a physical hydrogel based on the hyaluronic acid derivative HYADD® 4, were evaluated using as reference a solution of the parent natural polysaccharide, hyaluronic acid. The rheological measurements were performed both in flow and oscillation regimes at the physiological frequency values of the knee, typically spanning the range from 0.5 Hz (walking frequency) to 3 Hz (running frequency). Moreover, the viscoelastic features of Hymovis® were compared with the market-available viscosupplementation products in view of its use in joint diseases.The different behavior of the investigated materials in crossover frequency measurements and in structure recovery experiments can be explained on the basis of the structural and dynamic properties of the polymeric systems. PMID:22433568

  20. Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid

    PubMed Central

    Bonnevie, Edward D.; Galesso, Devis; Secchieri, Cynthia; Cohen, Itai; Bonassar, Lawrence J.

    2015-01-01

    When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants. PMID:26599797

  1. 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. PMID:26935813

  2. Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression

    PubMed Central

    2014-01-01

    Background Hyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study’s objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management. Methods We assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts. Results We showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier. Conclusions For the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks. PMID:24739440

  3. 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

  4. Improvement of tear trough by monophasic hyaluronic Acid and calcium hydroxylapatite.

    PubMed

    Wollina, Uwe

    2014-10-01

    Tear trough deformities are a sign of facial aging. The anatomical base is well understood. In many patients, minimal invasive surgical procedures are useful to improve appearance. Here, the authors describe the use of monophasic hyaluronic acid dermal filler and calcium hydroxylapatite injection for correction. Forty female patients with a mean age of 50 years have been treated. On average, an improvement of one class of Hidman's severity score could be achieved by single treatment. Mean duration of the effect was 10.1 months for hyaluronic acid and 12.8 months for calcium hydroxylapatite. Adverse effects were mild and temporary. Patients satisfaction was high (95%). PMID:25371770

  5. 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

  6. Development and characterization of microemulsions containing hyaluronic acid.

    PubMed

    Alkrad, Jamal Alyoussef; Mrestani, Yahya; Neubert, Reinhard H H

    2016-04-30

    Tween80 and Span20 were used as surfactant mixture for developing non-ionic microemulsions (MEs) containing hyaluronic acid 22 kDa (HA). The effect of Tween80:Span20 ratio (T:S ratio) on microemulsion (ME) water intake and stability was studied. Moreover, the effect of HA on the consumed surfactant amount which is for stabilizing the MEs, for reducing water intake was investigated. Two W/O MEs containing HA were optimized. The first ME was composed of 2% HA, 13.8% Tween:80:Span20 (2:3), 4.2% water and 79.9% isopropylpalmitate (IPP). The second was composed of 2% HA, 16% Span20, 9.6% water:dimethyl sulfoxide (W:DMSO) (6:3.6) and 72.4% medium chain triglycerides (MCTG). The droplet sizes of MEs were determined using dynamic light scattering (DLS). The multilayer membrane system (MLMS) was used for testing the release of HA from both MEs and the released amount of HA was quantified using capillary zone electrophoresis (CZE). Furthermore, three phase diagrams and relevant rheological characteristics were generated. The droplet size of the ME without HA decreased and increased with increasing the temperature. Furthermore, the droplet size of the IPP-ME and MCTG-ME without HA and of the MCTG-ME with HA decreased with increasing temperature. In contrast to this results, the droplet size of the IPP-ME with HA increased with increased temperature. This ME belongs to the Newtonian fluids. Compared to the first ME, the second ME shows droplet sizes at 25 °C of 6.5 nm without and 37 nm with HA. The droplet size in the second ME decreased proportionally with an increase of the temperature with and without HA. The release of HA was faster from the IPP ME compared to the MCTG-ME. The two developed MEs were stable, isotropic and their properties comply with ME properties concerning the droplet size and viscosity. PMID:26902172

  7. 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. PMID:20843434

  8. 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. PMID:20193782

  9. 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. PMID:26776822

  10. Identification and Characterization of CPS1 as a Hyaluronic Acid Synthase Contributing to the Pathogenesis of Cryptococcus neoformans Infection▿

    PubMed Central

    Jong, Ambrose; Wu, Chun-Hua; Chen, Han-Min; Luo, Feng; Kwon-Chung, Kyung J.; Chang, Yun C.; LaMunyon, Craig W.; Plaas, Anna; Huang, Sheng-He

    2007-01-01

    Cryptococcus neoformans is a pathogenic yeast that often causes devastating meningoencephalitis in immunocompromised individuals. We have previously identified the C. neoformans CPS1 gene, which is required for a capsular layer on the outer cell wall. In this report, we investigate the function of the CPS1 gene and its pathogenesis. We demonstrated that treatment of yeast with either 4-methylumbelliferone or hyaluronidase resulted in a reduction of the level of C. neoformans binding to human brain microvascular endothelial cells (HBMEC). Yeast extracellular structures were also altered accordingly in hyaluronidase-treated cells. Furthermore, observation of yeast strains with different hyaluronic acid contents showed that the ability to bind to HBMEC is proportional to the hyaluronic acid content. A killing assay with Caenorhabditis elegans demonstrated that the CPS1 wild-type strain is more virulent than the cps1Δ strain. When CPS1 is expressed in Saccharomyces cerevisiae and Escherichia coli, hyaluronic acid can be detected in the cells. Additionally, we determined by fluorophore-assisted carbohydrate electrophoretic analysis that hyaluronic acid is a component of the C. neoformans capsule. The size of hyaluronic acid molecules is evaluated by gel filtration and transmission electron microscopy studies. Together, our results support that C. neoformans CPS1 encodes hyaluronic acid synthase and that its product, hyaluronic acid, plays a role as an adhesion molecule during the association of endothelial cells with yeast. PMID:17545316

  11. Reproductive outcome after autocrosslinked hyaluronic acid gel application in infertile patients who underwent laparoscopic myomectomy.

    PubMed

    Pellicano, Massimiliano; Guida, Maurizio; Bramante, Silvia; Acunzo, Giuseppe; Di Spiezio Sardo, Attilio; Tommaselli, Giovanni A; Nappi, Carmine

    2005-02-01

    Autocrosslinked hyaluronic acid gel is useful for preventing postsurgical adhesion formation in infertile patients who have undergone laparoscopic myomectomy, and it increases the pregnancy rate more than laparoscopic myomectomy alone. Moreover, pregnancy rate is significantly higher with the use of subserous sutures. PMID:15705404

  12. Hyaluronic acid reagent suppressed endometriotic lesion formation in a mouse model.

    PubMed

    Hasegawa, Akiko; Yoshino, Osamu; Osuga, Yutaka; Kodama, Ako; Takamura, Masashi; Nishii, Osamu; Taketani, Yuji

    2010-05-15

    In an animal endometriosis model, the administration of hyaluronic acid (HA) reagent significantly suppressed the formation of endometriotic lesions in both number and weight. This effect was found when HA treatment was conducted at the time of endometrial fragment inoculation. PMID:20356589

  13. 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. PMID:25666331

  14. Midfacial rejuvenation by hyaluronic acid fillers and subcutaneous adipose tissue--a new concept.

    PubMed

    Wollina, Uwe

    2015-04-01

    In midface rejuvenation, hyaluronic acid (HA) fillers are commonly used as a versatile tool to improve appearance and to correct V-deformities and loss of volume. The induction of collagen as a major constituent of extracellular matrix (ECM) has been considered to be a basic effect of the rejuvenation procedure. Although commonly described as "dermal" soft fillers, histologic studies localized HA filler in the subcutaneous adipose tissue. Deep injection whenever possible lead to prolonged efficacy. Since volumizing HA filler induce mechanical stress not only to fibroblasts but adipocytes and deep injection itself causes minor trauma in the subcutaneous adipose tissue we suggest that the activation of adipose tissue-derived mesenchymal stem cells (ADMSC) is responsible for the observed clinical effects. We present a concept of filler action that discusses interactions of HA with adipocytes, ECM fiber network and ADMSC. Such a concept can explain the prolonged efficacy of deep midfacial filler placement and offers a new understanding to tailor HA fillers in the future. PMID:25665858

  15. 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

  16. The management of biofilm formation after hyaluronic acid gel filler injections: a review

    PubMed Central

    DUMITRAŞCU, DINU I.; GEORGESCU, ALEXANDRU V.

    2013-01-01

    Background and aim One of the most popular procedures of facial fillers in recent years has become the use of hyaluronic acid (HA). However, this method may be associated with local side effects of different severity. Many of them are not due to allergies, as previously believed, but to the formation of biofilm. We review the current knowledge on biofilm after HA. Methods All pertinent full text papers retrieved from PubMed under search words: “biofilm”, “hyaluronic acid”, “dermal fillers”, “hyaluronic acid complications” and “hyaluronic acid side effects” were analyzed; 29 of 60 articles were selected fro analysis. Results Local infections were reported: 13 cases are attributable to the activation of the biofilm. Clinical evolution is generally mild. Therapy should avoid NSAID and is based on the administration of antibiotics, oral corticosteroids, or 5-Flourouracil. Removal of HA with hyaluronidase has also been proposed. Conclusions The use of HA in cosmetic procedures might be accompanied by local adverse effects attributable to biofilm formation. This usually has a mild evolution, but in special cases requires specific therapy. PMID:26527945

  17. 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. PMID:21446328

  18. 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. PMID:27151670

  19. Enhanced affinity of ketotifen toward tamarind seed polysaccharide in comparison with hydroxyethylcellulose and hyaluronic acid: a nuclear magnetic resonance investigation.

    PubMed

    Uccello-Barretta, Gloria; Nazzi, Samuele; Balzano, Federica; Di Colo, Giacomo; Zambito, Ylenia; Zaino, Chiara; Sansò, Marco; Salvadori, Eleonora; Benvenuti, Marco

    2008-08-01

    Nuclear magnetic resonance (NMR) spectroscopy demonstrated that, in aqueous solution, ketotifen fumarate bound more strongly to tamarind seed polysaccharide (TSP) than to hydroxyethylcellulose or hyaluronic acid. Results were confirmed by dynamic dialysis technique. PMID:18595715

  20. DNA/polyethyleneimine/hyaluronic acid small complex particles and tumor suppression in mice.

    PubMed

    Ito, Tomoko; Yoshihara, Chieko; Hamada, Katsuyuki; Koyama, Yoshiyuki

    2010-04-01

    The highest barriers for non-viral vectors to an efficient in vivo gene transfection would be (1) non-specific interaction with biological molecules, and (2) large size of the DNA complex particles. Protective coating of the DNA/polyethyleneimine (PEI) complexes by hyaluronic acid (HA) effectively diminished the adverse interactions with biological molecules. Here we found HA also protected the DNA/PEI complexes against aggregation and inactivation through lyophilization-and-rehydration procedures. It allows us to prepare the concentrated very small DNA complex particles (<70 nm) suspension by preparing the complexes at highly diluted conditions, followed by lyophilized-and-rehydrated to a small volume. In vivo gene expression efficiency of the small complex was examined with mice subcutaneously inoculated with B16 melanoma cells. These formulations showed high reporter-gene expression level in tumor after intravenous injection into tumor-bearing mice. Small complex was then made of the plasmid encoding GM-CSF gene, and injected into the mice bearing subcutaneous solid B16 tumor. After intravenous injection, it induced apparent tumor growth suppression in 50% of the mice. Notably, significant therapeutic effect was detected in the mice that received intratumoral injection, and 75% of the mice were completely cured with disappearance of tumor. PMID:20047759

  1. 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.

  2. Enhanced topical delivery of hyaluronic acid encapsulated in liposomes: A surface-dependent phenomenon.

    PubMed

    Vázquez-González, Martha L; Calpena, Ana C; Domènech, Òscar; Montero, M Teresa; Borrell, Jordi H

    2015-10-01

    In the present study, we investigated the release and permeation of hyaluronic acid (HA) encapsulated in liposomes when deposited onto two surfaces: cellulose, a model widely used for investigating transport of drugs; and human skin, a natural biointerface used for transdermal drug delivery. We prepared and characterised liposomes loaded with HA and liposomes incorporating two penetration enhancers (PEs): the non-ionic surfactant Tween 80, and Transcutol P, a solubilising agent able to mix with polar and non-polar solvents. In vitro and ex vivo permeation assays showed that PEs indeed enhance HA-release from liposomes. Since one of the possible mechanisms postulated for the action of liposomes on skin is related to its adsorption onto the stratum corneum (SC), we used atomic force microscopy (AFM) topography and force volume (FV) analysis to investigate the structures formed after deposition of liposome formulations onto the investigated surfaces. We explored the possible relationship between the formation of planar lipid structures on the surfaces and the permeation of HA. PMID:26142626

  3. Key importance of compression properties in the biophysical characteristics of hyaluronic acid soft-tissue fillers.

    PubMed

    Gavard Molliard, Samuel; Albert, Séverine; Mondon, Karine

    2016-08-01

    Hyaluronic acid (HA) soft-tissue fillers are the most popular degradable injectable products used for correcting skin depressions and restoring facial volume loss. From a rheological perspective, HA fillers are commonly characterised through their viscoelastic properties under shear-stress. However, despite the continuous mechanical pressure that the skin applies on the fillers, compression properties in static and dynamic modes are rarely considered. In this article, three different rheological tests (shear-stress test and compression tests in static and dynamic mode) were carried out on nine CE-marked cross-linked HA fillers. Corresponding shear-stress (G', tanδ) and compression (E', tanδc, normal force FN) parameters were measured. We show here that the tested products behave differently under shear-stress and under compression even though they are used for the same indications. G' showed the expected influence on the tissue volumising capacity, and the same influence was also observed for the compression parameters E'. In conclusion, HA soft-tissue fillers exhibit widely different biophysical characteristics and many variables contribute to their overall performance. The elastic modulus G' is not the only critical parameter to consider amongst the rheological properties: the compression parameters E' and FN also provide key information, which should be taken into account for a better prediction of clinical outcomes, especially for predicting the volumising capacity and probably the ability to stimulate collagen production by fibroblasts. PMID:27093589

  4. Science of Hyaluronic Acid Beyond Filling: Fibroblasts and Their Response to the Extracellular Matrix.

    PubMed

    Landau, Marina; Fagien, Steven

    2015-11-01

    Loss of viscoelasticity is one of the primarily signs of skin aging, followed by appearance of visible wrinkles. Hyaluronic acid (HA)-based fillers are widely used to fill wrinkles and compensate for volume loss. Recent clinical observations demonstrate persistence of the filling effect longer than the biological availability of the filler. Stimulation of new collagen by cross-linked HA and up-regulation of elastin have been suggested as possible explanation to this observation and have been supported experimentally. Cross-linked HA substitutes for fragmented collagen in restoring extracellular matrix required for normal activity of fibroblasts, such as collagen and elastin production. To restore extracellular matrix efficiently, serial monthly treatments are required. Boosting of facial and nonfacial skin through fibroblast activation is a new indication for HA-based products. Injectable HA has also been recently registered in Europe as agents specific for the improvement of skin quality (Restylane Skinboosters). Further explanation of the possible mechanisms supported by long-term clinical examples is presented herein. PMID:26441098

  5. Efficacy of the Mineral Oil and Hyaluronic Acid Mixture Eye Drops in Murine Dry Eye

    PubMed Central

    Choi, Jung Han; Kim, Jung Han; Li, Zhengri; Oh, Han Jin; Ahn, Kyu Youn

    2015-01-01

    Purpose To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). Methods Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. Results There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. Conclusions The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE. PMID:25829831

  6. Hyaluronic acid gel ( Juvéderm™) preparations in the treatment of facial wrinkles and folds

    PubMed Central

    Allemann, Inja Bogdan; Baumann, Leslie

    2008-01-01

    Soft tissue augmentation with temporary dermal fillers is a continuously growing field, supported by the ongoing development and advances in technology and biocompatibility of the products marketed. The longer lasting, less immunogenic and thus more convenient hyaluronic acid (HA) fillers are encompassing by far the biggest share of the temporary dermal filler market. Since the approval of the first HA filler, Restylane®, there are at least 10 HA fillers that have been approved by the FDA. Not all of the approved HA fillers are available on the market, and many more are coming. The Juvéderm™ product line (Allergan, Irvine, CA), consisting of Juvéderm™ Plus and Juvéderm™ Ultra Plus, was approved by the FDA in 2006. Juvéderm™ is a bacterium-derived nonanimal stabilized HA. Juvéderm™ Ultra and Ultra Plus are smooth, malleable gels with a homologous consistency that use a new technology called “Hylacross™ technology”. They have a high concentration of cross-linked HAs, which accounts for its longevity. Juvéderm™ Ultra Plus is used for volumizing and correcting deeper folds, whereas Juvéderm™ Ultra is best for contouring and volumizing medium depth facial wrinkles and lip augmentation. Various studies have shown the superiority of the HA filler products compared with collagen fillers for duration, volume needed, and patient satisfaction. Restylane®, Perlane®, and Juvéderm™ are currently the most popular dermal fillers used in the United States. PMID:19281055

  7. 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.

  8. 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. PMID:26302663

  9. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid.

    PubMed

    Souza Felix Bravo, Bruna; Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-12-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  10. Delayed-type Necrosis after Soft-tissue Augmentation with Hyaluronic Acid

    PubMed Central

    Klotz De Almeida Balassiano, Laila; Roos Mariano Da Rocha, Camila; Barbosa De Sousa Padilha, Carolina; Martinezt Torrado, Carolina; Teixeira Da Silva, Roberta; Carlos Regazzi Avelleira, João

    2015-01-01

    The growing use of dermal fillers, specifically the use of hyaluronic acid, can be explained by their effectiveness and versatility as well as their favorable safety profiles. Nevertheless, early and late complications with varying levels of severity may occur. The incidence of complications is low and the majority of adverse events are mild (edema, erythema, and local ecchymosis) and of limited duration. However, more severe events, such as ischemia and necrosis, may occur. The symptoms of ischemia can occur immediately after the injection or several hours after the procedure. Here, the authors report three cases of necrosis after hyaluronic acid injection with the first symptoms presenting only several hours after the procedure. The patients were treated immediately after the diagnosis. The aim of this review is to communicate the possibility of the delayed-type presentation of necrosis, present the signs and symptoms that lead to early diagnosis, and review the treatment possibilities of this severe complication. PMID:26705447

  11. 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. PMID:25665867

  12. 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. PMID:26163839

  13. Incorporation of TGF-beta 3 within collagen-hyaluronic acid scaffolds improves their chondrogenic potential.

    PubMed

    Matsiko, Amos; Levingstone, Tanya J; Gleeson, John P; O'Brien, Fergal J

    2015-06-01

    Incorporation of therapeutics in the form of growth factors within biomaterials can enhance their biofunctionality. Two methods of incorporating transforming growth factor-beta 3 within collagen-hyaluronic acid scaffolds are described, markedly improving mesenchymal stem cell-mediated chondrogenic differentiation and matrix production. Such scaffolds offer control over the release of therapeutics, demonstrating their potential for repair of complex chondral defects requiring additional stimuli. PMID:25800862

  14. Use of hyaluronic acid fillers for the treatment of the aging face

    PubMed Central

    Gold, Michael H

    2007-01-01

    Hyaluronic acid fillers have become popular soft tissue filler augmentation agents over the past several years. They have helped revolutionize the filler market with a number of new products available for use for our patients. The purpose of this manuscript is to review the characteristics of the HA fillers and to review each of the current products currently available for use in the US. PMID:18044187

  15. Diplopia after hyaluronic acid gel injection for correction of facial tear trough deformity.

    PubMed

    Kashkouli, Mohsen Bahmani; Heirati, Abtin; Pakdel, Farzad; Kiavash, Victoria

    2012-10-01

    A 38 Year-old-female presented with diplopia and bilateral lower eyelid swelling 1.5 months after hyaluronic acid filler injection of tear trough deformity. Comprehensive eye examination showed an inferior oblique muscle restriction on the right eye. Diplopia and bilateral lower eyelid puffiness were treated by injection of hyaluronidase which resulted in disappearance of both diplopia and bilateral lower eyelid puffiness. PMID:22571493

  16. [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. PMID:15195524

  17. 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

  18. Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.

    PubMed

    El Kechai, Naila; Mamelle, Elisabeth; Nguyen, Yann; Huang, Nicolas; Nicolas, Valérie; Chaminade, Pierre; Yen-Nicolaÿ, Stéphanie; Gueutin, Claire; Granger, Benjamin; Ferrary, Evelyne; Agnely, Florence; Bochot, Amélie

    2016-03-28

    The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner. PMID:26860286

  19. Efficacy of a New Topical Nano-hyaluronic Acid in Humans

    PubMed Central

    Jegasothy, S. Manjula; Zabolotniaia, Valentina; Bielfeldt, Stephan

    2014-01-01

    Background: The aim of this study was to evaluate the efficacy of a new topical low molecular nano-hyaluronic acid preparation in treating wrinkles, skin hydration, and skin elasticity in humans. Methods: Thirty-three women with an average age of 45.2 were studied for a period of eight weeks to measure the anti-wrinkle efficacy of a new nano-hyaluronic acid. The measurements were performed in the periorbital regions by investigating the three-dimensional structure using a DermaTOP for wrinkles, Corneometer for skin hydration, Cutometer for skin elasticity, and a Chroma Meter for erythema. Thereafter, standardized images were taken and evaluated by six selected and trained raters at the end of the study for reduction of visible wrinkles as well as skin color uniformity and pigmentation. Results: The results of the study showed a statistically significant moisturizing effect of the product range (lotion, serum, and cream, after 2,4, and 8 weeks of treatment. Measurement of skin roughness showed a significantly finer skin structure after two weeks of treatment, and skin elasticity showed a significant improvement after 2 and 8 weeks of treatment. Conclusion: The new nano-hyaluronic acid clearly demonstrated a significant benefit in decreasing the depth of wrinkles (up to 40%), and skin hydration (up to 96%) and skin firmness and elasticity were significantly enhanced (up to 55%) at the end of eight weeks. PMID:24688623

  20. 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. PMID:24211959

  1. Hyaluronic acid-quercetin conjugate micelles: synthesis, characterization, in vitro and in vivo evaluation.

    PubMed

    Pang, Xin; Lu, Zhen; Du, Hongliang; Yang, Xiaoye; Zhai, Guangxi

    2014-11-01

    A tumor cell-targeted prodrug was developed for quercetin, using hyaluronic acid as polymeric carrier. Hyaluronic acid-quercetin (HA-QT) bioconjugates were synthesized by linking the hydroxy of quercetin via a succinate ester to adipic dihydrazide-modified hyaluronic acid. The mirco-morphology demonstrated that the prepared prodrug could form self-assembled micelles possessing spherical shape, 172.1 nm average diameter and -20.30 mV surface potential. The HA-QT micelles exhibited significant sustained and pH-dependent drug release behaviors without dramatic initial burst. Compared to free quercetin solution, the HA-QT micelles were found a 4 times increase in cytotoxicity on MCF-7 cells (CD44-overexpressing cell lines), while weak enhancement in inhibitory activity was observed towards L929 cells (CD44 deficient cell lines). Promisingly, 20.1-fold increase in the half-life and 4.9-fold increase in the area-under-the-curve (AUC) of quercetin were achieved for the HA-QT micelles compared with the parent drug. In addition, the HA-QT micelles also showed excellent inhibition effect on tumor growth in H22 tumor-bearing mice. Hemolytic toxicity and vein irritation assay further suggested that the HA-QT micelles were a safe and potent drug delivery system for targeted antitumor therapy. PMID:25454664

  2. 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.

  3. Correction of Tear Trough Deformity With a Cohesive Polydensified Matrix Hyaluronic Acid: A Case Series.

    PubMed

    Huber-Vorländer, Jürgen; Kürten, Martin

    2015-01-01

    The tear trough or infraorbital hollow is a challenging area to treat, and only a few fillers are suitable for this delicate area. We report on a European case series of six subjects with mild to severe tear troughs who received treatment with cohesive polydensified matrix (CPM®) technology hyaluronic acid gel (Belotero® Balance). The product was injected as small depots (up to ten small boli 0.2 mL maximum each per side) at the supraperiosteal level along or below the orbital rim. Follow-up visits took place at 1, 3, 6, and 9 months after injection for independent evaluation of the clinical effect using the Merz Aesthetics Scale™ for infraorbital hollows and the Global Aesthetic Improvement Scale. Adverse events were also recorded. Mean hollowness scores were considerably improved compared with baseline in all subjects. In all women, the improvements remained throughout the 9-month study, with none reverting to their baseline score. Subjects' satisfaction with treatment was very high throughout the study, and all women stated that they would repeat treatment with the same product. The CPM hyaluronic acid gel was well tolerated. CPM hyaluronic acid gel is a safe and effective treatment for the tear trough area. PMID:26605822

  4. Correction of tear trough deformity with a cohesive polydensified matrix hyaluronic acid: a case series.

    PubMed

    Huber-Vorländer, Jürgen; Kürten, Martin

    2015-01-01

    The tear trough or infraorbital hollow is a challenging area to treat, and only a few fillers are suitable for this delicate area. We report on a European case series of six subjects with mild to severe tear troughs who received treatment with cohesive polydensified matrix (CPM(®)) technology hyaluronic acid gel (Belotero(®) Balance). The product was injected as small depots (up to ten small boli 0.2 mL maximum each per side) at the supraperiosteal level along or below the orbital rim. Follow-up visits took place at 1, 3, 6, and 9 months after injection for independent evaluation of the clinical effect using the Merz Aesthetics Scale™ for infraorbital hollows and the Global Aesthetic Improvement Scale. Adverse events were also recorded. Mean hollowness scores were considerably improved compared with baseline in all subjects. In all women, the improvements remained throughout the 9-month study, with none reverting to their baseline score. Subjects' satisfaction with treatment was very high throughout the study, and all women stated that they would repeat treatment with the same product. The CPM hyaluronic acid gel was well tolerated. CPM hyaluronic acid gel is a safe and effective treatment for the tear trough area. PMID:26170706

  5. Correction of tear trough deformity with a cohesive polydensified matrix hyaluronic acid: a case series

    PubMed Central

    Huber-Vorländer, Jürgen; Kürten, Martin

    2015-01-01

    The tear trough or infraorbital hollow is a challenging area to treat, and only a few fillers are suitable for this delicate area. We report on a European case series of six subjects with mild to severe tear troughs who received treatment with cohesive polydensified matrix (CPM®) technology hyaluronic acid gel (Belotero® Balance). The product was injected as small depots (up to ten small boli 0.2 mL maximum each per side) at the supraperiosteal level along or below the orbital rim. Follow-up visits took place at 1, 3, 6, and 9 months after injection for independent evaluation of the clinical effect using the Merz Aesthetics Scale™ for infraorbital hollows and the Global Aesthetic Improvement Scale. Adverse events were also recorded. Mean hollowness scores were considerably improved compared with baseline in all subjects. In all women, the improvements remained throughout the 9-month study, with none reverting to their baseline score. Subjects’ satisfaction with treatment was very high throughout the study, and all women stated that they would repeat treatment with the same product. The CPM hyaluronic acid gel was well tolerated. CPM hyaluronic acid gel is a safe and effective treatment for the tear trough area. PMID:26170706

  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. Cytokine regulation of human lung fibroblast hyaluronan (hyaluronic acid) production. Evidence for cytokine-regulated hyaluronan (hyaluronic acid) degradation and human lung fibroblast-derived hyaluronidase.

    PubMed Central

    Sampson, P M; Rochester, C L; Freundlich, B; Elias, J A

    1992-01-01

    We characterized the mechanisms by which recombinant (r) tumor necrosis factor (TNF), IFN-gamma, and IL-1, alone and in combination, regulate human lung fibroblast hyaluronic acid (HA) production. Each cytokine stimulated fibroblast HA production. The combination of rTNF and rIFN-gamma resulted in a synergistic increase in the production of high molecular weight HA. This was due to a synergistic increase in hyaluronate synthetase activity and a simultaneous decrease in HA degradation. In contrast, when rTNF and rIL-1 were combined, an additive increase in low molecular weight HA was noted. This was due to a synergistic increase in hyaluronate synthetase activity and a simultaneous increase in HA degradation. Human lung fibroblasts contained a hyaluronidase that, at pH 3.7, depolymerized high molecular weight HA to 10-40 kD end products of digestion. However, hyaluronidase activity did not correlate with fibroblast HA degradation. Instead, HA degradation correlated with fibroblast-HA binding, which was increased by rIL-1 plus rTNF and decreased by rIFN-gamma plus rTNF. Recombinant IL-1 and rTNF weakly stimulated and rIL-1 and rTNF in combination further augmented the levels of CD44 mRNA in lung fibroblasts. In contrast, rIFN-gamma did not significantly alter the levels of CD44 mRNA in unstimulated or rTNF stimulated cells. These studies demonstrate that rIL-1, rTNF, and rIFN-gamma have complex effects on biosynthesis and degradation which alter the quantity and molecular weight of the HA produced by lung fibroblasts. They also show that fibroblast HA degradation is mediated by a previously unrecognized lysosomal-type hyaluronidase whose function may be regulated by altering fibroblast-HA binding. Lastly, they suggest that the CD44 HA receptor may be involved in this process. Images PMID:1401082

  8. Change of hyaluronic acid synthesis during differentiation of myogenic cells and its relation to transformation of myoblasts by Rous sarcoma virus.

    PubMed

    Yoshimura, M

    1985-05-01

    Hyaluronic acid synthesis was examined in cultures of differentiating chick embryo muscle cells before, during and after fusion. Prior to fusion, hyaluronic acid was synthesized and secreted into the medium, but once fusion began this synthesis was reduced significantly. Synthesis then increased again after completion of fusion. Thus, production of hyaluronic acid was lowest at the time of or right before cell fusion. When myoblasts were transformed by Rous sarcoma virus (RSV), a higher amount of hyaluronic acid was synthesized, and cells were not able to fuse. The turnover rate of hyaluronic acid might be different between myotubes and RSV-transformed myoblasts. The addition of exogenous hyaluronic acid to myoblast cultures resulted in the partial inhibition of fusion. The effect was reversible because fusion took place after removal of the exogenous hyaluronic acid. These observations suggest that hyaluronic acid plays an important role in the differentiation of myogenic cells, and that elevated hyaluronic acid synthesis may partly be the reason for inhibition of myotube formation upon transformation by Rous sarcoma virus. PMID:2988797

  9. 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. PMID:26106949

  10. 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.

  11. 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

  12. Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler.

    PubMed

    Moon, Du Geon; Kwak, Tae Il; Kim, Je Jong

    2015-08-01

    Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure. PMID:26331121

  13. 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

  14. Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler

    PubMed Central

    Kwak, Tae Il; Kim, Je Jong

    2015-01-01

    Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure. PMID:26331121

  15. Efficacy, Safety, and Tolerance of a New Injection Technique for High- and Low-Molecular-Weight Hyaluronic Acid Hybrid Complexes

    PubMed Central

    Palmieri, Beniamino; Coacci, Alessandro

    2015-01-01

    Objective: Facial aging is characterized by skin laxity and loss of skin elasticity. Hyaluronic acid, a biological component of the extracellular matrix, whose level decreases during aging, plays structural, rheological, and physiological roles in the skin. Hyaluronic acid may possess different molecular weights: low-molecular-weight hyaluronic acid (from 50 kDa) and high-molecular-weight hyaluronic acid (just up to 2 million kDa). This monocentric, retrospective, observational study investigates the efficacy, security, and tolerability of a new injective low- and high-molecular-weight hyaluronic acid for facial skin rejuvenation. Methods: Eleven women received once a month, for 2 months, 2 mL of the product in the subcutaneous layer of the right and left malar/submalar areas. Facial skin echography, facial skin hydration, elasticity, and transepidermal water loss were assessed before (T0), after 1 month (T1), and after 3 months of treatment (T2). The injective features of the product, physician subjective satisfaction, and patient satisfaction were also reported. Results: Facial face hydration, elasticity, and transepidermal water loss values significantly improved at T1 and T2 (P < .01). Patients were very satisfied at the end of the treatment, and the compound's profit evaluated by the physician was optimal in the absence of local side effects. Conclusions: This treatment represents a good treatment option to restore vitality and turgidity of skin presenting the signs of aging in the absence of intolerance symptoms. PMID:26491508

  16. Separation and purification of hyaluronic acid by embedded glucuronic acid imprinted polymers into cryogel.

    PubMed

    Ünlüer, Özlem Biçen; Ersöz, Arzu; Denizli, Adil; Demirel, Rasime; Say, Rıdvan

    2013-09-01

    Hyaluronic acid (HA) has been used in many applications such as pharmaceutical, clinical and cosmetics, so its separation and purification is very important. In this study, firstly d-glucuronic acid imprinted polymers (MIPs) have been synthesized for the separation of HA which has glucuronic acid part in its structure. MIP particles have characterized by elemental analysis, Fourier Transform Infrared Spectroscopy (FT-IR) and swelling tests. Then, synthesized MIP particles have embedded into polyacrylamide based cryogel. Cryogel has prepared by free radical cryogelation process initiated by N,N,N',N'-Tetramethylethylenediamine (TEMED) and ammonium persulfate (APS) as redox initiators. This cryogel material was characterized by FT-IR, swelling tests, scanning electron microscopy (SEM) and surface adsorption analyze including pore size analyzer (BET) method. The adsorption of HA has investigated by spectrophotometric method using MIPs embedded into cryogel columns (GAIPEC) and the maximum HA adsorption capacity was found to be 318mgg(-1). The selectivity of GAIPEC column has estimated using N-acetylglucose amine as interfering agent since this molecule is a part of HA and the results have shown that GAIPEC has been nearly 35 times selective for HA than N-acetylglucose amine. The optimum chromatographic conditions for separation of HA were investigated. pH 7.0 buffer solution for elution and 0.1M of NaCl solution as desorption agent were used at 0.5mLmin(-1) flow rate. Also, recovery of GAIPEC was investigated and the results have shown that GAIPEC could be used many times without decreasing its adsorption capacity significantly. Here in, combining selectivity of MIP particles and mechanical properties of cryogel, a rigid and stable material was prepared for the separation and purification of HA. To point out this, HA has been isolated from fish eye and fermentation of Streptococcus equi RSKK 679 cell culture. After that, it has characterized and Fast Protein Liquid

  17. Multilayered, Hyaluronic Acid-Based Hydrogel Formulations Suitable for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Cocultures.

    PubMed

    Engel, Brian J; Constantinou, Pamela E; Sablatura, Lindsey K; Doty, Nathaniel J; Carson, Daniel D; Farach-Carson, Mary C; Harrington, Daniel A; Zarembinski, Thomas I

    2015-08-01

    Validation of a high-throughput compatible 3D hyaluronic acid hydrogel coculture of cancer cells with stromal cells. The multilayered hyaluronic acid hydrogels improve drug screening predictability as evaluated with a panel of clinically relevant chemotherapeutics in both prostate and endometrial cancer cell lines compared to 2D culture. PMID:26059746

  18. Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties.

    PubMed

    Piluso, Susanna; Hiebl, Bernhard; Gorb, Stanislav N; Kovalev, Alexander; Lendlein, Andreas; Neffe, Axel T

    2011-02-01

    Biopolymers of the extracellular matrix are attractive starting materials for providing degradable and biocompatible biomaterials. In this study, hyaluronic acid-based hydrogels with tunable mechanical properties were prepared by the use of copper- catalyzed azide-alkyne cycloaddition (known as "click chemistry"). Alkyne-functionalized hyaluronic acid was crosslinked with linkers having two terminal azide functionalities, varying crosslinker density as well as the lengths and rigidity of the linker molecules. By variation of the crosslinker density and crosslinker type, hydrogels with elastic moduli in the range of 0.5-4 kPa were prepared. The washed materials contained a maximum of 6.8 mg copper per kg dry weight and the eluate of the gel crosslinked with diazidostilbene did not show toxic effects on L929 cells. The hyaluronic acid-based hydrogels have potential as biomaterials for cell culture or soft tissue regeneration applications. PMID:21374560

  19. [Effects of two UDP-glucose dehydrogenases on hyaluronic acid biotransformation].

    PubMed

    GuoI, Donghui; Han, Jian; Liu, Weifeng; Fu, Zhenzhou; Zhu, Qizhong; Tao, Yong

    2014-11-01

    We amplified genes encoding UDP-glucose dehydrogenase, ecohasB from Escherichia coli and spyhasB from Streptococcus pyogenes. Both ecohasB and spyhasB were inserted into T7 expression vector pRX2 to construct recombinant plasmids pRXEB and pRXSB, and to express in E. coli BL21(DE3). After nickel column purification of UDP-glucose dehydrogenases, the enzymes were characterized. The optimum reaction condition of spyHasB was at 30 °C and pH 10. The specific activity reached 12.2 U/mg under optimum condition. The optimum reaction condition of ecoHasB was at 30 °C and pH 9. Its specific activity reached 5.55 U/mg under optimum condition. The pmuhasA gene encoding hyaluronic acid synthase was amplified from Pasteurella multocida and ligated with ecohasB and spyhasB to construct the coexpression vectors pBPAEB and pBPASB, respectively. The co-expression vectors were transformed into E. coli BW25113. Hyaluronic acid (HA) was produced by biotransformation and the conditions were optimized. When recombinant strains were used to produce hyaluronic acid, the higher the activity of UDP-glucose dehydrogenase was, the better its stability was, and the higher the HA production could reach. Under the optimal conditions, the yields of HA produced by pBPAEB/BW25113 and pBPASB/BW25113 in shake flasks were 1.52 and 1.70 g/L, respectively, and the production increased more than 2-3 folds as previously reported. PMID:25985520

  20. 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.

  1. 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. PMID:12010437

  2. 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.

  3. A novel use of reticulated hyaluronic acid (Healaflow) for hypotony eyes in patients with uveitis.

    PubMed

    Stead, R E; Juma, Z; Turner, S; Jones, L D; Sung, V C T

    2016-06-01

    Persistent ocular hypotony is a complex and ongoing challenge faced in ophthalmology. It can result in early ocular phthisis and associated visual decline, pain and deformity. We present the first case series, in which repeated intracameral injections of highly reticulated hyaluronic acid (Healaflow) have successfully prevented the complications of ocular hypotony in the long term. We believe it is a viable management option that can bring about a significant improvement to the quality of life in this subgroup of patients while avoiding frequent intervention. PMID:27016504

  4. Treatment of glabella skin necrosis following injection of hyaluronic acid filler using platelet-rich plasma.

    PubMed

    Kang, Boo Kyoung; Kang, In Jung; Jeong, Ki Heon; Shin, Min Kyung

    2016-01-01

    Hyaluronic acid (HA) fillers have been widely used for soft-tissue augmentation. However, there can be various complications following HA filler injection. Skin necrosis is rare but one of the most disastrous side effects that, if not treated promptly and effectively, can result in permanent and potentially disfiguring scarring. Thus, early proper management is important. Herein we report a patient who experienced tissue necrosis of the glabellar area after receiving filler injections that was successfully treated using platelet-rich plasma and provide full follow-up clinical photographs. PMID:26052808

  5. [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. PMID:16060327

  6. Hyaluronic acid used for the correction of nasal deviation in an 18-year-old Middle Eastern man.

    PubMed

    Piggott, J R; Yazdani, A

    2011-01-01

    The use of fillers for nonsurgical rhinoplasty has advanced in both materials and methods, and continues to gain popularity in North America. This technique is most often used for secondary revisions, although reports of fillers used in primary rhinoplasty in selected patients have been recently described. The present report details the use of a hyaluronic acid dermal filler in a young Middle Eastern man for a post-traumatic crooked nose deformity. Primary correction of the patient's right-sided nasal bone deviation using hyaluronic acid as a soft tissue filler was achieved with excellent results and patient satisfaction. The current use of fillers in nasal contouring is reviewed. PMID:23204891

  7. 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.

  8. 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. PMID:26954089

  9. 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.

  10. 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

  11. 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. PMID:26986163

  12. 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

  13. Preparation and characterization of nanoparticles based on histidine-hyaluronic acid conjugates as doxorubicin carriers.

    PubMed

    Wu, Jing-liang; Liu, Chen-guang; Wang, Xiao-lei; Huang, Zhen-hua

    2012-08-01

    Histidine-hyaluronic acid (His-HA) conjugates were synthesized using hyaluronic acid (HA) as a hydrophilic segment and histidine (His) as hydrophobic segment by 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) mediated coupling reactions. The structural characteristics of the His-HA conjugates were investigated using (1)H NMR. His-HA nanoparticles (HH-NPs) were prepared based on His-HA conjugates, and the characteristics of HH-NPs were investigated using dynamic light scattering, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and fluorescence spectroscopy. The particles were between 342 and 732 nm in size, depending on the degree of substitution (DS) of the His. TEM and SEM images indicated that the morphology of HH-NPs was spherical in shape. The critical aggregation concentrations of HH-NPs ranged from 0.034 to 0.125 mg/ml, which decreased with an increase in the DS of the His. Images of fluorescence microscopy indicate that HH-NPs were taken up by the cancer cell line (MCF-7), and significantly decreased by competition inhibition of free HA. From the cytotoxicity test, it was found that DOX-loaded HH-NPs exhibited similar dose and time-dependent cytotoxicity against MCF-7 cells with free DOX. PMID:22580754

  14. Fabrication and in vitro evaluation of stable collagen/hyaluronic acid biomimetic multilayer on titanium coatings

    PubMed Central

    Ao, Haiyong; Xie, Youtao; Tan, Honglue; Yang, Shengbing; Li, Kai; Wu, Xiaodong; Zheng, Xuebin; Tang, Tingting

    2013-01-01

    Layer-by-layer (LBL) self-assembly technique has been proved to be a highly effective method to immobilize the main components of the extracellular matrix such as collagen and hyaluronic acid on titanium-based implants and form a polyelectrolyte multilayer (PEM) film by electrostatic interaction. However, the formed PEM film is unstable in the physiological environment and affects the long-time effectiveness of PEM film. In this study, a modified LBL technology has been developed to fabricate a stable collagen/hyaluronic acid (Col/HA) PEM film on titanium coating (TC) by introducing covalent immobilization. Scanning electron microscopy, diffuse reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the PEM film. Results of Sirius red staining demonstrated that the chemical stability of PEM film was greatly improved by covalent cross-linking. Cell culture assays further illustrated that the functions of human mesenchymal stem cells, such as attachment, spreading, proliferation and differentiation, were obviously enhanced by the covalently immobilized Col/HA PEM on TCs compared with the absorbed Col/HA PEM. The improved stability and biological properties of the Col/HA PEM covalently immobilized TC may be beneficial to the early osseointegration of the implants. PMID:23635490

  15. The Design of In Vitro Liver Sinusoid Mimics Using Chitosan–Hyaluronic Acid Polyelectrolyte Multilayers

    PubMed Central

    Kim, Yeonhee; Larkin, Adam L.; Davis, Richey M.

    2010-01-01

    Interactions between hepatocytes and liver sinusoidal endothelial cells (LSECs) are essential for the development and maintenance of hepatic phenotypic functions. We report the assembly of three-dimensional liver sinusoidal mimics comprised of primary rat hepatocytes, LSECs, and an intermediate chitosan–hyaluronic acid polyelectrolyte multilayer (PEM). The height of the PEMs ranged from 30 to 55 nm and exhibited a shear modulus of ∼100 kPa. Hepatocyte–PEM cellular constructs exhibited stable urea and albumin production over a 7-day period, and these values were either higher or similar to cells cultured in a collagen sandwich. This is of significance because the thickness of a collagen gel is ∼1000-fold higher than the height of the chitosan–hyaluronic acid PEM. In the hepatocyte–PEM–LSEC liver-mimetic cellular constructs, LSEC phenotype was maintained, and these cultures exhibited stable urea and albumin production. CYP1A1/2 activity measured over a 7-day period was significantly higher in the hepatocyte–PEM–LSEC constructs than in collagen sandwich cultures. A 16-fold increase in CYP1A1/2 activity was observed for hepatocyte–PEM–10,000 LSEC samples, thereby suggesting that interactions between hepatocytes and LSECs are critical in enhancing the detoxification capability in hepatic cultures in vitro. PMID:20491586

  16. Posterior Ciliary Artery Occlusion Caused by Hyaluronic Acid Injections Into the Forehead

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:26986163

  17. Retinal Branch Artery Embolization Following Hyaluronic Acid Injection: A Case Report.

    PubMed

    Chen, Wei; Wu, Lin; Jian, Xing-Ling; Zhang, Bin; Li, Jin-Ying; Qin, Xiao-Lei; Yu, Bo

    2016-07-01

    Injection of hyaluronic acid (HA) filler is a common aesthetic procedure. Impairment of vision, although rare, is a devastating complication of this procedure, which may not be reversible. We report on a patient who experienced visual acuity impairment and ischemic oculomotor nerve palsy after injection of HA into the nasal dorsum. In this case, clinical signs improved within 14 days of treatment. We also provide a review of the mechanism, clinical features, risk factors, and prevention and treatment strategies relating to embolization of ocular circulation after injection of HA. Vision loss is a rare but devastating complication of injection of hyaluronic acid (HA) in the face. Visual acuity seldom recovers completely. We report on a 22-year-old Asian woman who experienced obstruction of a branch of the retinal artery after injection of HA to augment her nose. The patient's visual acuity declined shortly after the procedure, and ophthalmoplegia occurred. Combination treatment was administered to restore the perfusion and oxygen supply to the retina and optic nerve. Within 14 days of rigorous treatment, the patient experienced improvement in visual acuity, extraocular movement, and visual field defects. LEVEL OF EVIDENCE 5: Risk. PMID:27075374

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

    PubMed

    Ondeck, Matthew G; Engler, Adam J

    2016-02-01

    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

  19. Proteome analysis of the hyaluronic acid-producing bacterium, Streptococcus zooepidemicus

    PubMed Central

    Marcellin, Esteban; Gruber, Christian W; Archer, Colin; Craik, David J; Nielsen, Lars K

    2009-01-01

    Background Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a commensal of horses and an opportunistic pathogen in many animals and humans. Some strains produce copious amounts of hyaluronic acid, making S. zooepidemicus an important industrial microorganism for the production of this valuable biopolymer used in the pharmaceutical and cosmetic industry. Encapsulation by hyaluronic acid is considered an important virulence factor in other streptococci, though the importance in S. zooepidemicus remains poorly understood. Proteomics may provide a better understanding of virulence factors in S. zooepidemicus, facilitate the design of better diagnostics and treatments, and guide engineering of superior production strains. Results Using hyaluronidase to remove the capsule and by optimising cellular lysis, a reference map for S. zooepidemicus was completed. This protocol significantly increased protein recovery, allowing for visualisation of 682 spots and the identification of 86 proteins using mass spectrometry (LC-ESI-MS/MS and MALDI-TOF/TOF); of which 16 were membrane proteins. Conclusion The data presented constitute the first reference map for S. zooepidemicus and provide new information on the identity and characteristics of the more abundantly expressed proteins. PMID:19327162

  20. Hyaluronic acid fat graft myringoplasty vs fat patch fat graft myringoplasty.

    PubMed

    Alzahrani, Musaed; Saliba, Issam

    2015-08-01

    We aim to compare the hyaluronic acid to fat graft myringoplasty (HAFGM) technique to a recently described modified-FGM (M-FGM) in the repair of tympanic membrane perforation (TMP). We also aim to evaluate the hearing level improvement postoperatively. We conducted a prospective study in an adult tertiary care center between 2012 and 2013. Adult patients presenting with simple TMP were operated on randomly using either HAFGM or M-FGM under local anesthesia in outpatients' settings. Success was considered when complete closure is achieved. Audiometric parameters were evaluated pre and postoperatively. Twenty-four patients were included in the study (HAFGM: 10 patients and M-FGM: 14 patients). Complete closure was achieved in 80 % in HAFGM vs 42.8 % in the M-FGM (p = 0.03). The study was abandoned due to the low success rate in first 14 patients of the M-FGM group. The pure tone audiometry was improved postoperatively in the HAFGM only. The study was aborted because of the unsatisfactory obtained results using the MFGM. It also shows the beneficial effect of hyaluronic acid application to FGM for a successful TMP repair. PMID:24633245

  1. Friction Force Microscopy of Lubricin and Hyaluronic Acid between Hydrophobic and Hydrophilic Surfaces

    PubMed Central

    Chang, Debby P.; Abu-Lail, Nehal I.; Coles, Jeffrey M.; Guilak, Farshid; Jay, Gregory D.; Zauscher, Stefan

    2010-01-01

    Lubricin and hyaluronic acid (HA), molecular constituents of synovial fluid, have long been theorized to play a role in joint lubrication and wear protection. While lubricin has been shown to function as a boundary lubricant, conflicting evidence exists as to the boundary lubricating ability of hyaluronic acid. Here, we use colloidal force microscopy to explore the friction behavior of these two molecules on the microscale between chemically uniform hydrophilic (hydroxyl-terminated) and hydrophobic (methyl-terminated) surfaces in physiological buffer solution. Behaviors on both surfaces are physiologically relevant since the heterogeneous articular cartilage surface contains both hydrophilic and hydrophobic elements. Friction between hydrophobic surfaces was initially high (μ=1.1, at 100nN of applied normal load) and was significantly reduced by lubricin addition while friction between hydrophilic surfaces was initially low (μ=0.1) and was slightly increased by lubricin addition. At lubricin concentrations above 200 µg/ml, friction behavior on the two surfaces was similar (μ=0.2) indicating that nearly all interaction between the two surfaces was between adsorbed lubricin molecules rather than between the surfaces themselves. In contrast, addition of HA did not appreciably alter the frictional behavior between the model surfaces. No synergistic effect on friction behavior was seen in a physiological mixture of lubricin and HA. Lubricin can equally mediate the frictional response between both hydrophilic and hydrophobic surfaces, likely fully preventing direct surface-to-surface contact at sufficient concentrations, whereas HA provides considerably less boundary lubrication. PMID:20936046

  2. Topical administration of hyaluronic acid in children with recurrent or chronic middle ear inflammations.

    PubMed

    Torretta, Sara; Marchisio, Paola; Rinaldi, Vittorio; Gaffuri, Michele; Pascariello, Carla; Drago, Lorenzo; Baggi, Elena; Pignataro, Lorenzo

    2016-09-01

    Hyaluronic acid (HA) treatment has been successfully performed in patients with recurrent upper airway infections or rhinitis. The aim of this study was to assess the efficacy and safety of the topical nasal administration of an HA-based compound by investigating its effects in children with recurrent or chronic middle ear inflammations and chronic adenoiditis. A prospective, single-blind, 1:1 randomised controlled study was performed to compare otoscopy, tympanometry and pure-tone audiometry in children which received the daily topical administration of normal 0.9% sodium chloride saline solution (control group) or 9 mg of sodium hyaluronate in 3 mL of a 0.9% sodium saline solution. The final analysis was based on 116 children (49.1% boys; mean age, 62.9 ± 17.9 months): 58 in the control group and 58 in the study group. At the end of follow-up, the prevalence of patients with impaired otoscopy was significantly lower in the study group (P value = 0.024) compared to baseline but not in the control group. In comparison with baseline, the prevalence of patients with impaired tympanometry at the end of the follow-up period was significantly lower in the study group (P value = 0.047) but not in the control group. The reduction in the prevalence of patients with conductive hearing loss (CHL) (P value = 0.008) and those with moderate CHL (P value = 0.048) was significant in the study group, but not in the control group. The mean auditory threshold had also significantly improved by the end of treatment in the study group (P value = 0.004) but not in the control group. Our findings confirm the safety of intermittent treatment with a topical nasal sodium hyaluronate solution and are the first to document its beneficial effect on clinical and audiological outcomes in children with recurrent or chronic middle ear inflammations associated with chronic adenoiditis. PMID:27481884

  3. New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels.

    PubMed

    Bulpitt, P; Aeschlimann, D

    1999-11-01

    Biodegradable materials for spatially and temporally controlled delivery of bioactive agents such as drugs, growth factors, or cytokines are key to facilitating tissue repair. We have developed a versatile method for chemical crosslinking high-molecular-weight hyaluronic acid under physiological conditions yielding biocompatible and biodegradable hydrogels. The method is based on the introduction of functional groups onto hyaluronic acid by formation of an active ester at the carboxylate of the glucuronic acid moiety and subsequent substitution with a side chain containing a nucleophilic group on one end and a (protected) functional group on the other. We have formed hyaluronic acid with amino or aldehyde functionality, and subsequently hydrogels with these hyaluronic acid derivatives and bifunctional crosslinkers or mixtures of the hyaluronic acid derivatives carrying different functionalities using active ester- or aldehyde-mediated reactions. Size analysis of the hyaluronic acid derivatives showed that the chemical modification did not lead to fragmentation of the polysaccharide. Hydrogels formed with hyaluronic acid derivatized to a varying degree and crosslinked with low- or high-molecular-weight crosslinkers were evaluated for biodegradability by digestion with hyaluronidase and for biocompatibility and ectopic bone formation by subcutaneous implantation in rats. Several hydrogel formulations showed excellent cell infiltration and chondro-osseous differentiation when loaded with bone morphogenetic protein-2 (BMP-2). Synergistic action of insulin-like growth factor-1 with BMP-2 promoted cartilage formation in this model, while addition of transforming growth factor-beta and BMP-2 led to rapid replacement of the matrix by bone. PMID:10449626

  4. Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A Streptococcus.

    PubMed

    Levin, J C; Wessels, M R

    1998-10-01

    The hyaluronic acid capsule of group A Streptococcus (GAS) is an important virulence factor, but little is known about mechanisms that regulate capsule expression. Transposon Tn916 mutagenesis of the poorly encapsulated M-type 3 GAS strain DLS003 produced a transconjugant that exhibited a mucoid colony morphology, reflecting increased hyaluronic acid capsule production. Analysis of chromosomal DNA sequence immediately downstream of the transposon insertion identified two open reading frames, designated csrR and csrS, which exhibited sequence similarity to bacterial two-component regulatory systems. We constructed an in-frame deletion mutation within csrR, which encodes the putative response component. Replacement of the native csrR gene in the DLS003 chromosome with the mutant allele resulted in a sixfold increase in capsule production and a corresponding increase in transcription of the has operon, which contains the essential genes for hyaluronic acid synthesis. Increased capsule production by the csrR mutant strain was associated with enhanced resistance to complement-mediated opsonophagocytic killing in vitro and with a 500-fold increase in virulence in mice. These results establish CsrR as a negative regulator of hyaluronic acid capsule synthesis and suggest that it is part of a two-component regulatory system that influences capsule expression and virulence. PMID:9786197

  5. Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies

    PubMed Central

    ORASAN, OLGA HILDA; CIULEI, GEORGE; COZMA, ANGELA; SAVA, MADALINA; DUMITRASCU, DAN LUCIAN

    2016-01-01

    Chronic liver diseases represent a significant public health problem worldwide. The degree of liver fibrosis secondary to these diseases is important, because it is the main predictor of their evolution and prognosis. Hyaluronic acid is studied as a non-invasive marker of liver fibrosis in chronic liver diseases, in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of fibrosis. We review the advantages and limitations of hyaluronc acid, a biomarker, used to manage patients with chronic viral hepatitis B or C infection, non-alcoholic fatty liver disease, HIV-HCV coinfection, alcoholic liver disease, primary biliary cirrhosis, biliary atresia, hereditary hemochromatosis and cystic fibrosis. PMID:27004022

  6. Nanometer-thick hyaluronic acid self-assemblies with strong adhesive properties.

    PubMed

    Marais, Andrew; Pendergraph, Samuel; Wågberg, Lars

    2015-07-22

    The adhesive characteristics of poly(allylamine hydrochloride) (PAH)/hyaluronic acid (HA) self-assemblies were investigated using contact adhesion testing. Poly(dimethylsiloxane) spheres and silicon wafers were coated with layer-by-layer (LbL) assemblies of PAH/HA. No increase in adhesion was observed when surfaces covered with dried LbL films were placed in contact. However, bringing the coated surfaces in contact while wet and separating them after drying resulted in an increase by a factor of 100 in the work of adhesion (from one to three bilayers). Herein we discuss the adhesion in PAH/HA and PAH/poly(acrylic acid) assemblies. PAH/HA assemblies have potential application as strong biomedical adhesives. PMID:26151110

  7. 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

  8. 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

  9. 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.

  10. Targeting cancer with hyaluronic acid-based nanocarriers: recent advances and translational perspectives.

    PubMed

    Cadete, Ana; Alonso, María José

    2016-09-01

    Hyaluronic acid is a natural polysaccharide that has been widely explored for the development of anticancer therapies due to its ability to target cancer cells. Moreover, advances made in the last decade have revealed the versatility of this biomaterial in the design of multifunctional carriers, intended for the delivery of a variety of bioactive molecules, including polynucleotides, immunomodulatory drugs and imaging agents. In this review, we aim to provide an overview of the major recent achievements in this field, highlighting the application of the newly developed nanostructures in combination therapies, immunomodulation and theranostics. Finally, we will discuss the main challenges and technological advances that will allow these carriers to be considered as candidates for clinical development. PMID:27526874

  11. [Aminoacids and hyaluronic acid in topical treatment of bedsores. Clinical report].

    PubMed

    Chiummariello, S; Arleo, S; Alfano, C

    2010-05-01

    Pressure ulcers are evolutive tissue of the skin, derma and subcutaneous layer. If not treated properly, but sometimes despite that, they may even reach muscles and bones. Nutritional status of the patient is the most important and potentially reversible factor which can contribute to wound recovery. Several studies underline in particular the importance of the proteic and caloric intake in order to stimulate the formation of granulation tissue and collagen. We thought giving the nutrients for wound repair directly on the wound bed, topically, therefore using the wound bed as exchange surface and presuming the wounded tissues are able to absorb, metabolize and ultimately use the aminoacids to repair the damage. The goal of our work is to describe the clinical case patient treated with a new active wound dressing releasing aminoacids and hyaluronic acid. PMID:20615371

  12. Mechanically Robust and Bioadhesive Collagen and Photocrosslinkable Hyaluronic Acid Semi-Interpenetrating Networks

    PubMed Central

    Brigham, Mark D.; Bick, Alexander; Lo, Edward; Bendali, Amel; Burdick, Jason A.

    2009-01-01

    In this work, we present a class of hydrogels that leverage the favorable properties of the photo-cross-linkable hyaluronic acid (HA) and semi-interpenetrating collagen components. The mechanical properties of the semi-interpenetrating-network (semi-IPN) hydrogels far surpass those achievable with collagen gels or collagen gel–based semi-IPNs. Furthermore, the inclusion of the semi-interpenetrating collagen chains provides a synergistic mechanical improvement over unmodified HA hydrogels. Collagen–HA semi-IPNs supported fibroblast adhesion and proliferation and were shown to be suitable for cell encapsulation at high levels of cell viability. To demonstrate the utility of the semi-IPNs as a microscale tissue engineering material, cell-laden microstructures and microchannels were fabricated using soft lithographic techniques. Given their enhanced mechanical and biomimetic properties, we anticipate that these materials will be of value in tissue engineering and three-dimensional cell culture applications. PMID:19105604

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

    PubMed

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

    2015-10-01

    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

  14. Hyaluronic acid biodegradable material for reconstruction of vascular wall: a preliminary study in rats.

    PubMed

    Pandis, Laura; Zavan, Barbara; Bassetto, Franco; Ferroni, Letizia; Iacobellis, Laura; Abatangelo, Giovanni; Lepidi, Sandro; Cortivo, Roberta; Vindigni, Vincenzo

    2011-02-01

    The objective of this preliminary study was to develop a reabsorbable vascular patch that did not require in vitro cell or biochemical preconditioning for vascular wall repair. Patches were composed only of hyaluronic acid (HA). Twenty male Wistar rats weighing 250-350 g were used. The abdominal aorta was exposed and isolated. A rectangular breach (1 mm × 5 mm) was made on vessel wall and arterial defect was repaired with HA made patch. Performance was assessed at 1, 2, 4, 8, and 16 weeks after surgery by histology and immunohistochemistry. Extracellular matrix components were evaluated by molecular biological methods. After 16 weeks, the biomaterial was almost completely degraded and replaced by a neoartery wall composed of endothelial cells, smooth muscle cells, collagen, and elastin fibers organized in layers. In conclusion, HA patches provide a provisional three-dimensional support to interact with cells for the control of their function, guiding the spatially and temporally multicellular processes of artery regeneration. PMID:21268111

  15. 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

  16. 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

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

    PubMed

    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

  18. 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. PMID:26769504

  19. Strong and Biostable Hyaluronic Acid-Calcium Phosphate Nanocomposite Hydrogel via in Situ Precipitation Process.

    PubMed

    Jeong, Seol-Ha; Koh, Young-Hag; Kim, Suk-Wha; Park, Ji-Ung; Kim, Hyoun-Ee; Song, Juha

    2016-03-14

    Hyaluronic acid (HAc) hydrogel exhibits excellent biocompatibility, but it has limited biomedical application due to its poor biomechanical properties as well as too-fast enzymatic degradation. In this study, we have developed an in situ precipitation process for the fabrication of a HAc-calcium phosphate nanocomposite hydrogel, after the formation of the glycidyl methacrylate-conjugated HAc (GMHA) hydrogels via photo-cross-linking, to improve the mechanical and biological properties under physiological conditions. In particular, our process facilitates the rapid incorporation of calcium phosphate (CaP) nanoparticles of uniform size and with minimal agglomeration into a polymer matrix, homogeneously. Compared with pure HAc, the nanocomposite hydrogels exhibit improved mechanical behavior. Specifically, the shear modulus is improved by a factor of 4. The biostability of the nanocomposite hydrogel was also significantly improved compared with that of pure HAc hydrogels under both in vitro and in vivo conditions. PMID:26878437

  20. Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery.

    PubMed

    Jang, Yeon Lim; Ku, Sook Hee; Jin, So; Park, Jae Hyung; Kim, Won Jong; Kwon, Ick Chan; Kim, Sun Hwa; Jeong, Ji Hoon

    2014-10-01

    The clinical applications of therapeutic siRNA remain as a challenge due to the lack of efficient delivery system. In the present study, hyaluronic acid-siRNA conjugate (HA-SS-siRNA)/reducible polyethylenimine (BPEI1.2k-SS) complexes were developed to efficiently deliver the siRNA to HA receptor abundant region with the improved siRNA stability. HA and siRNA were conjugated with disulfide bonds, which are cleavable in cytoplasm. The synthesized HA-SS-siRNA was further complexed with BPEI1.2k-SS, resulting in the formation of spherical nanostructures with approximately 190 nm of size and neutral surface charge. HA-SS-siRNA/BPEI1.2k-SS complexes exhibited the improved stability against serum proteins or polyanions. These complexes were successfully translocated into intracellular region via HA receptor-mediated endocytosis, and silenced target gene expression. PMID:25942799

  1. Hyaluronic acid grafting mitigates calcification of glutaraldehyde-fixed bovine pericardium.

    PubMed

    Ohri, Rachit; Hahn, Sei K; Hoffman, Allan S; Stayton, Patrick S; Giachelli, Cecilia M

    2004-08-01

    Pathologic calcification is the leading cause of the clinical failure of glutaraldehyde-fixed bovine pericardium used in bioprosthetic valves. A novel surface modification of glutaraldehyde fixed bovine pericardium was carried out with high molecular weight hyaluronic acid (HA). HA was chemically modified with adipic dihydrazide (ADH) to introduce hydrazide functional groups onto the HA backbone. Glutaraldehyde-fixed bovine pericardium (GFBP) was modified by grafting this HA to the free aldehyde groups on the tissue via the hydrazide groups. Following a 2-week subcutaneous implantation in osteopontin (OPN)-null mice, the calcification of HA-modified bovine pericardium was drastically reduced (by 84.5%) compared to positive controls (tissue without HA-modification) (p = 0.005). The calcification-mitigating effect of HA surface modification was also confirmed by microscopic analysis of explanted tissue stained with Alizarin Red S for calcium. PMID:15227678

  2. Controlled synthesis and inclusion ability of a hyaluronic acid derivative bearing beta-cyclodextrin molecules.

    PubMed

    Charlot, Aurélia; Heyraud, Alain; Guenot, Pierre; Rinaudo, Marguerite; Auzély-Velty, Rachel

    2006-03-01

    A new synthetic route to beta-cyclodextrin-linked hyaluronic acid (HA-CD) was developed. This was based on the preparation of a HA derivative selectively modified with adipic dihydrazide (HA-ADH) and a beta-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction. The CD-polysaccharide was fully characterized in terms of chemical integrity and purity by high-resolution NMR spectroscopy. The complexation ability of the grafted CD was further demonstrated by isothermal titration calorimetry using sodium adamantane acetate (ADAc) and Ibuprofen as model guest molecules. The thermodynamic parameters for the complexation of these negatively charged guest molecules by the beta-CD grafted on negatively charged HA were shown to be largely influenced by the ionic strength of the aqueous medium. PMID:16529430

  3. 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.

  4. Emergent Molecular Recognition through Self-Assembly: Unexpected Selectivity for Hyaluronic Acid among Glycosaminoglycans.

    PubMed

    Noguchi, Takao; Roy, Bappaditya; Yoshihara, Daisuke; Sakamoto, Junji; Yamamoto, Tatsuhiro; Shinkai, Seiji

    2016-05-01

    Oligophenylenevinylene (OPV)-based fluorescent (FL) chemosensors exhibiting linear FL responses toward polyanions were designed. Their application to FL sensing of glycosaminoglycans (heparin: HEP, chondroitin 4-sulfate: ChS, and hyaluronic acid: HA) revealed that the charge density encoded as the unit structure directs the mode of OPV self-assembly: H-type aggregate for HEP with 16-times FL increase and J-type aggregate for HA with 93-times FL increase, thus unexpectedly achieving the preferential selectivity for HA in contrast to the conventional HEP selective systems. We have found that the integral magnitude of three factors consisting of binding mechanism, self-assembly, and FL response can amplify the structural information on the target input into the characteristic FL output. This emergent property has been used for a novel molecular recognition system that realizes unconventional FL sensing of HA, potentially applicable to the clinical diagnosis of cancer-related diseases. PMID:27060601

  5. Facile method to prepare silk fibroin/hyaluronic acid films for vascular endothelial growth factor release.

    PubMed

    Zhou, Juan; Zhang, Bin; Liu, Xunwei; Shi, Lijun; Zhu, Jun; Wei, Daixu; Zhong, Jian; Sun, Gang; He, Dannong

    2016-06-01

    A facile approach was proposed to prepare silk fibroin (SF) and hyaluronic acid (HA) composite films from aqueous solution without crosslinking or any post treatment. Only by controlling the HA content and film formation temperature during the film casting, the HA/SF films with different composition were prepared. The films were then characterized by structural characteristics, thermal stability, morphology, water stability, water absorption, mechanical properties. After immersing in water for 24h, all of the films showed good structural integrity. The degradation rate of the HA/SF films in protease XIV can be controlled by changing the film formation temperature and HA content. Decreasing the temperature and adding HA resulted in the rapid release of VEGF (vascular endothelial growth factor) from the HA/SF films. Overall, the 5% HA/SF films formed at 37°C with more rapid VEGF release exhibited great potential in drug delivery, especially when the rapid vascularization was needed. PMID:27083373

  6. Electrical behavior of polymer hydrogel composed of poly(vinyl alcohol)/hyaluronic acid in solution

    NASA Astrophysics Data System (ADS)

    Kim, Seon Jeong; Yoon, Seoung Gil; Park, Sang Jun; Lee, Chang Kee; Shin, Su Ryon; Lee, Young Moo; Kim, In Young; Kim, Sun I.

    2003-07-01

    Interpenetrating polymer networks (IPN) composed of poly(vinyl alcohol) (PVA) and hyaluronic acid (HA) were prepared and exhibited electrical sensitive behavior. The swelling behavior of the PVA/HA IPN was studied by immersion of the gel in aqueous NaCl solutions at various concentrations and pHs. Also, the stimuli response of the PVA/HA IPN in electric fields was investigated. When swollen IPN was placed between a pair of electrodes, the PVA/HA IPN exhibited bending behavior upon the application of an electric field. The PVA/HA IPN also showed stepwise bending behavior depending on the electric stimulus. Also, for using biomedical application, the bending behavior of PVA/HA IPN has been studied in hank"s solution at pH 7.4

  7. Hyaluronic Acid-Based Nanocarriers for Intracellular Targeting: Interfacial Interactions with Proteins in Cancer

    PubMed Central

    Choi, Ki Young; Saravanakumar, Gurusamy; Park, Jae Hyung; Park, Kinam

    2011-01-01

    The therapeutic efficacy of most drugs is greatly depends on their ability to cross the cellular barrier and reach their intracellular target sites. To transport the drugs effectively through the cellular membrane and to deliver them into the intracellular environment, several interesting smart carrier systems based on both synthetic or natural polymers have been designed and developed. In recent years, hyaluronic acid (HA) has emerged as a promising candidate for intracellular delivery of various therapeutic and imaging agents because of its innate ability to recognize specific cellular receptors that overexpressed on diseased cells. The aim of this review is to highlight the significance of HA in cancer, and to explore the recent advances of HA-based drug carriers towards cancer imaging and therapeutics. PMID:22079699

  8. Hyaluronic acid-functionalized mesoporous silica nanoparticles for efficient photodynamic therapy of cancer cells.

    PubMed

    Gary-Bobo, Magali; Brevet, David; Benkirane-Jessel, Nadia; Raehm, Laurence; Maillard, Philippe; Garcia, Marcel; Durand, Jean-Olivier

    2012-09-01

    Mesoporous silica nanoparticles (MSN) for photodynamic therapy (PDT) were coated with poly-(L-lysine) and hyaluronic acid (HA) by using the layer-by-layer method. HA is able to target cancer cells over-expressing the corresponding CD44 receptor. MSN functionalized with HA (MSN-HA) were more efficient than MSN without the targeting moiety when PDT was performed at low fluence (14 Jcm(-2)) and low dosage of MSN (20 μgmL(-1)) on HCT 116 colorectal cancer cells, known to over-express the CD44 receptor. Incubation of HCT-116 cancer cells with an excess of HA impaired the PDT effect with MSN-HA thus demonstrating that an active endocytosis mechanism was involved in the uptake of MSN-HA by these cells. PMID:22959805

  9. Surface functionalization of styrenic block copolymer elastomeric biomaterials with hyaluronic acid via a "grafting to" strategy.

    PubMed

    Li, Xiaomeng; Luan, Shifang; Yuan, Shuaishuai; Song, Lingjie; Zhao, Jie; Ma, Jiao; Shi, Hengchong; Yang, Huawei; Jin, Jing; Yin, Jinghua

    2013-12-01

    As a biostable elastomer, the hydrophobicity of styrenic block copolymer (SBC) intensely limits its biomedical applications. In order to overcome such shortcoming, the SBC films were grafted with hyaluronic acid (HA) using a coupling agent. The surface chemistry of the modified films was examined by ATR-FTIR and XPS techniques, and the surface morphology was visually described by AFM. The biological performances of the HA-modified films were evaluated by a series of experiments, such as protein adsorption, platelet adhesion, and in vitro cytocompatibility. It was found that the HA-modified samples showed a low adhesiveness to fibroblast at the initial stage; however, it stimulated the growth of fibroblast. The L929 fibroblast growth presented a strong dependence on the molecular weight (MW) of HA. The samples modified with 17kDa HA exhibited the worst wettability and platelet adhesion, while providing the best results of supporting fibroblast proliferation. PMID:23974002

  10. Topical diclofenac/hyaluronic acid gel in the treatment of solar keratoses.

    PubMed

    McEwan, L E; Smith, J G

    1997-11-01

    A randomized double-blind controlled trial of 130 patients was performed to study the efficacy and tolerability of topical 3% diclofenac in 2.5% hyaluronic acid (HA) gel (active) versus gel containing 2.5% HA alone (control) in the treatment of solar keratoses. Patients were asked to apply trial gel to the target lesion twice a day and also sunscreen once a day for 24 weeks. The complete response rates were 29% for the active gel and 17% for the control gel. The difference was not statistically significant (P = 0.14). A high percentage of patients in both groups experienced a partial response to treatment (38% active, 45% control) but there was no significant difference in the spectrum of response between the two treatments (P = 0.18). Local adverse reactions occurred significantly more frequently in patients using the active gel (29% compared to 5% using control gel, P = 0.0002). PMID:9431711

  11. 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. PMID:27287553

  12. Self-assembling and auto-crosslinkable hyaluronic acid hydrogels with a fibrillar structure.

    PubMed

    Palumbo, F S; Pitarresi, G; Albanese, A; Calascibetta, F; Giammona, G

    2010-01-01

    A hyaluronic acid derivative bearing pendant L-benzoyl-cysteine portions (with a derivatization degree equal to 10 mol.%) was synthesized by linking N,N'-dibenzoyl-L-cystine to the polysaccharide and then reducing its disulfide bridge to thiol groups. The formation of pi-pi stacking interactions between the benzoyl moieties was studied by fluorescence spectroscopy as a function of polymer concentration and oxidation time. The efficiency of oxidation of thiol groups to disulfide bridges occurring in phosphate buffer pH 7.4, was determined by colorimetric assays. The hydrogel formed by means of oxidative crosslinking has shown the presence of fibrillar aggregates as detected by light and scanning electron microscopy. Human derm fibroblasts were encapsulated into hydrogel-forming solution, and their ability to proliferate was tested during 3 days of culture. PMID:19531387

  13. Construction of hyaluronic acid noisome as functional transdermal nanocarrier for tumor therapy.

    PubMed

    Kong, Ming; Park, Hyunjin; Feng, Chao; Hou, Lin; Cheng, Xiaojie; Chen, Xiguang

    2013-04-15

    To develop a functional nanosized transdermal drug delivery system for tumor therapy, amphiphilic hyaluronic acid (HA) based niosome was constructed combining transdermal and tumor targeting ability in one entity. HA esterified with monostearin, the conjugate labeled as HA-GMS self-assembled onto niosome surface and formed HA-niosome. The multilayer vesicle had small size (around 40 nm), good stability and desirable drug encapsulating efficacy, and well compatible with blood. It exhibited better endocytosis to mouse breast tumor cell (4T1) than the control chitosan nanoparticle, which was verified qualitatively and quantitatively. Skin permeation of HA-niosome was proven to be efficient using in vitro stratum corneum model and in vivo fluorescence observation. Histological section study confirmed the security and efficiency of transdermal permeation. The results evidence HA-niosome to be exciting and promising for tumor therapy through trandermal administration. PMID:23544584

  14. Scaffolds of Hyaluronic Acid-Poly(Ethyl Acrylate) Interpenetrating Networks: Characterization and In Vitro Studies.

    PubMed

    Rodríguez-Pérez, E; Lloret Compañ, A; Monleón Pradas, M; Martínez-Ramos, C

    2016-08-01

    Hyaluronic acid (HA) provides many advantages to regenerative implants through its bioactive properties, but it also has many limitations as a biomaterial if it is not chemically modified. In order to overcome some of these limitations, HA has been combined with poly(ethyl acrylate) in the form of interpenetrating polymeric networks (IPNs), in which the HA network is crosslinked with divinyl sulfone. Scaffolds of this IPN have been produced through a template-leaching methodology, and their properties have been compared with those of single-network scaffolds made of either PEA or crosslinked HA. A fibroblast cell line has been used to assess the in vitro performance of the scaffolds, revealing good cell response and a differentiated behavior on the IPN surface when compared to the individual polymers. Altogether, the results confirm that this type of material offers an interesting microenvironment for cells, which can be further improved toward its potential use in medical implants. PMID:27072058

  15. 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.

  16. Hyaluronic acid (Sperm Select) improves retention of sperm motility and velocity in normospermic and oligospermic specimens.

    PubMed

    Huszar, G; Willetts, M; Corrales, M

    1990-12-01

    The effects of Sperm Select (Pharmacia AB, Uppsala, Sweden), a hyaluronic acid medium, on the motility and membrane integrity properties of sperm were studied. In 15 normospermic specimens after overnight incubation, the motility parameters in the control versus the Sperm Select group were as follows (mean +/- SEM): motility, 18.8% +/- 2.8% versus 27.4% +/- 2.9%; velocity, 21.5 +/- 2.4 versus 27.2 +/- 2.2 microns/s; linearity, 3.8 +/- 0.3 versus 4.4 +/- 0.2; lateral head displacement, 1.5 +/- 0.2 versus 1.9 +/- 0.1 microns; and tail beat/cross frequency, 8.8 +/- 1.3 versus 10.8 +/- 1.4 Hz. The density of motile sperm was 10.8 +/- 2.3 versus 18.5 +/- 2.5 X 10(6) sperm/mL. Finally, the velocity coefficient, the multiple of the sperm motility and linear velocity, was 4.6 +/- 1.1 versus 8.1 +/- 1.4. However, we found no Sperm Select related differences when testing sperm membrane integrity with hypoosmotic swelling and supravital staining. Thus, Sperm Select improves the retention of sperm motility (most prominently velocity) apparently due to a direct action of hyaluronic acid on sperm metabolism or contractility rather than to preservation of sperm membrane integrity. In 20 oligospermic specimens, Sperm Select caused similar improvements in sperm motility, and the duration of motility could be predicted from the degree of enhancement in sperm velocity after short-term Sperm Select exposure. A modified Sperm Select protocol is described that further increases motile sperm yield without a centrifugation step. PMID:1700958

  17. High pressure liquid chromatographic identification of hyaluronic acid and chondroitin sulphate disaccharides.

    PubMed

    Zebrower, M; Kieras, F J; Heaney-Kieras, J

    1991-06-01

    In this report we describe a system capable of resolving all of the known unsaturated disaccharides derived from the chondroitin sulphates, dermatan sulphate and hyaluronic acid by chondroitinase digestion. This system is superior to others in that the non-sulphated and mono-, di- and tri-sulphated disaccharides can be separated with good resolution in approximately 40 min in an isocratic solvent. The system employs an amino-cyano silica gel column (Whatman Partisil 5 PAC, 25 cm) and is eluted with an isocratic solvent consisting of 48% (v/v) acetonitrile, 14% (v/v) methanol and 38% (v/v) aqueous buffer. This aqueous buffer contains 0.5 M Tris-HCl, 0.1 M boric acid, 23.4 mM sulphuric acid, pH 8.0. UV absorption is monitored at 229 nm and for most disaccharides as little as 150 ng can be reliably determined. The addition of boric acid to the eluent is essential for good resolution of all components and the addition of low concentrations of sulphuric acid is used to control the elution times of various components. The system was applied to the analysis of glycosaminoglycan standards and excellent agreement with previous compositional analyses was obtained. PMID:1794040

  18. Multi-functionalized hyaluronic acid nanogels crosslinked with carbon dots as dual receptor-mediated targeting tumor theranostics.

    PubMed

    Jia, Xu; Han, Yu; Pei, Mingliang; Zhao, Xubo; Tian, Kun; Zhou, Tingting; Liu, Peng

    2016-11-01

    Hyaluronic acid (HA)-based theranostic nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking the folate-terminated poly(ethylene glycol) modified hyaluronic acid (FA-PEG-HA) with carbon dots (CDs) for the first time. Due to the extraordinary fluorescence property of the integrated CDs, the theranostic nanogels could be used for the real-time and noninvasive location tracking to cancer cells. HA could load Doxorubicin (DOX) via electrostatic interaction with a drug-loading capacity (DLC) of 32.5%. The nanogels possessed an ideal release of DOX in the weak acid environment, while it was restrained in the neutral media, demonstrating the pH-responsive controlled release behavior. The cytotoxicity and cellular uptake results clearly illustrated that most DOX was released and accumulated in the cell nuclei and killed the cancer cells efficaciously, due to their dual receptor-mediated targeting characteristics. PMID:27516286

  19. Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip

    PubMed Central

    Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Martin, Timothy J.; Domb, Benjamin G.

    2016-01-01

    The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection—local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814

  20. Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip.

    PubMed

    Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S Pavan; Martin, Timothy J; Domb, Benjamin G

    2016-04-01

    The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection-local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814

  1. Review of long-term adverse effects associated with the use of chemically-modified animal and nonanimal source hyaluronic acid dermal fillers

    PubMed Central

    Edwards, Paul C; Fantasia, John E

    2007-01-01

    Although only recently introduced, chemically-modified hyaluronic acid dermal fillers have gained widespread acceptance as “redefining” dermal fillers in the fields of dermatology and cosmetic facial surgery. Although hyaluronic acid-based dermal fillers have a low overall incidence of long term side effects, occasional adverse outcomes, ranging from chronic lymphoplasmacytic inflammatory reactions to classic foreign body-type granulomatous reactions have been documented. These long-term adverse events are reviewed. PMID:18225451

  2. 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

  3. Inhaled hyaluronic acid as ancillary treatment in children with bacterial acute rhinopharyngitis.

    PubMed

    Varricchio, A; Capasso, M; Avvisati, F; Varricchio, A M; De Lucia, A; Brunese, F P; Ciprandi, G

    2014-01-01

    Acute rhinopharyngitis (ARP) is the most common upper respiratory infection in children and represents a social problem for both the pharmaco-economic impact and a burden for the family. Topical antibiotic therapy is usually effective in bacterial ARP, but ancillary treatment might improve its efficacy. Hyaluronic acid (HA) is a promising molecule that has been recently proposed in upper respiratory disorders. Therefore, the purpose of this study was to evaluate the effects of ancillary HA treatment in children with bacterial ARP. Globally, 51 children (27 males, mean age 5.9 ± 2.1 years) with bacterial ARP were enrolled in the study. At baseline, children were randomly assigned to the treatment with: 125 mg of thiamphenicol diluted in 4 mL of saline isotonic solution twice daily (group A) or with 125 mg of thiamphenicol plus 4 ml of sodium hyaluronate 0.2% plus xylitol 5% (Aluneb, Sakura Italia) twice daily (group B) administered by the nasal device Rinowash (Airliquide Medical System, Italy) and connected to an aerosol nebulizer with pneumatic compressor (1.5 bar per 5 L/min) Nebula (Airliquide Medical System, Italy), for 10 days. sVAS, nasopharyngeal spotting, neutrophils and bacteria were assessed at baseline and after the treatment. Both treatments induced significant reduction of symptom perception, spotting, neutrophil and bacteria count. However, thiamphenicol plus HA was able to significantly induce a greater effect on sVAS (p=0.006), neutrophil count (p=0.01), and bacteria count (p=0.0003) than thiamphenicol alone. In conclusion, this study provides the first evidence that intranasal HA, as ancillary treatment, may be able to improve topical antibiotic efficacy in children with bacterial ARP. PMID:25316142

  4. 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

  5. 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. PMID:26855049

  6. 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

  7. In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model.

    PubMed

    Yeo, Yoon; Highley, Christopher B; Bellas, Evangelia; Ito, Taichi; Marini, Robert; Langer, Robert; Kohane, Daniel S

    2006-09-01

    We studied the efficacy of an in situ cross-linked hyaluronic acid hydrogel (HAX) in preventing post-surgical peritoneal adhesions, using a rabbit sidewall defect-cecum abrasion model. Two cross-linkable precursors were prepared by modifying hyaluronic acid with adipic dihydrazide and aldehyde, respectively. The hydrogel precursors cross-linked to form a flexible hydrogel upon mixing. The hydrogel was biodegradable and provided a durable physical barrier, which was highly effective in reducing the formation of post-operative adhesions. Ten out of 12 animals in the untreated control group developed fibrous adhesions requiring sharp dissection, while only 2 out of 8 animals treated with HAX gels showed such adhesions, and those occurred in locations that were not covered by the hydrogel. We also studied means by which gel degradation time can be modulated by varying the precursor concentration and molecular weight. PMID:16750564

  8. 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

  9. Inactivation of the cysteine protease SpeB affects hyaluronic acid capsule expression in group A streptococci.

    PubMed

    Woischnik, M; Buttaro, B A; Podbielski, A

    2000-04-01

    The human pathogen Streptococcus pyogenes expresses several virulence factors that are required for the pathogens survival within the host and the concomitant development of disease. To examine the influence of one virulence factor, the extracellular cysteine protease SpeB, on the expression of other virulence factors, the speB structural gene of a serotype M3 and M49 strain was inactivated. Morphologic examination, quantification of extracellular hyaluronic acid capsule, and Northern blot analysis of the isogenic speB -mutants revealed a strain-dependent decrease of hyaluronic acid capsule production and an increase in superoxide dismutase transcription. The transcription of streptolysin O (slo), di- and oligo-peptide permease (dpp, opp), hyaluronidase (hyl), streptokinase (ska) and streptococcal pyrogenic exotoxin A (speA) was unaffected. PMID:10764613

  10. Comparison of Puerariae Radix and its hydrolysate on stimulation of hyaluronic acid production in NHEK cells.

    PubMed

    Wen, Kuo-Ching; Lin, Shiuan-Pey; Yu, Chung-Ping; Chiang, Hsiu-Mei

    2010-01-01

    Hyaluronic acid (HA) is present in high concentrations in the intercellular spaces of the epidermis and the connective tissues of the dermis. It is associated with many beneficial biological activities including water retention, maintenance of various cellular functions, and skin homeostasis. Puerariae Radix (PR), a Chinese herb and a popular food in Asia, is used for various medicinal purposes including anti-hypertension, anti-angina pectoris and anti-dipsotropic. PR is rich in isoflavone glycosides like genistin and daidzin as soya. In this study, Bifidobactericum breve CCRC 14061 and CCRC 11846 were used for the fermentation of PR; moreover, acid was used to hydrolyze PR decoction. Genistein and daidzein in the hydrolysate were determined by HPLC. The HA production in normal human epidermal keratinocytes (NHEK) was measured after 48 hours incubation with PR and its hydrolysate, respectively. HA was assayed by enzyme-linked immunosorbent assay (ELISA), and retinoic acid was used as the positive control. After fermentation with Bifidobactericum breve, the contents of daidzein and genistein were increased 785% and 1,010% by CCRC 14061, and 192% and 406% by CCRC 11846, respectively, whereas after acid hydrolysis, only daidzein was increased by 990%. The production of HA in NHEK was increased after incubation with the fermentation product of CCRC 14061, acid hydrolysate, PR decoction and retinoic acid (22+/- 0.2%), whereas no increase of HA concentration was found after incubation with the fermentation product of CCRC 11846. Furthermore, the PR hydrolysate stimulated the HA production of NHEK, and the effect was dose-dependent (18.6%-83.9%). In conclusion, PR preparations would stimulate HA production in NHEK cells which might be used as a new cosmetic ingredient in moisturizers and an anti-aging agent. PMID:20128051

  11. 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.

  12. Desire for penile girth enhancement and the effects of the self-injection of hyaluronic Acid gel.

    PubMed

    Coskuner, Enis Rauf; Canter, Halil Ibrahim

    2012-07-01

    Penile girth enhancement is a controversial subject but demands for enhancement are increasing steadily. Although various fillers have been widely used for soft tissue augmentation, there is no reliable material for this particular situation. Here we report a case of an acute hypersensitivity reaction in a man after his first self-injection of a filler material, which, he claimed, was hyaluronic acid gel for penile girth enhancement and glans penis augmentation. PMID:23112518

  13. Self-consistent field theory investigation of the behavior of hyaluronic acid chains in aqueous salt solutions

    NASA Astrophysics Data System (ADS)

    Nogovitsin, E. A.; Budkov, Yu. A.

    2012-04-01

    In this work we continue to develop a field-theoretic methodology, which combines the technique of Gaussian equivalent representation for the calculation of functional integrals with the continuous Gaussian thread model of flexible polymers for solving statistical-mechanical problems of polyelectrolyte solutions. We present new analytic expressions for the osmotic pressure, the potential of mean force, and the monomer-monomer pair distribution function, and employ them to investigate the structural and thermodynamic quantities of the polyelectrolyte system. We demonstrate the applicability of the method for systems of polyelectrolyte chains in which the monomers interact via a Yukawa-type pair potential. As a specific example, the present work focuses on aqueous solutions of hyaluronic acid with added salts NaCl and CaCl2. Hyaluronic acid is a high molecular weight linear polysaccharide, which has a multitude of roles in biological tissues. We conclude that the effect of sodium chloride and calcium chloride on the osmotic properties of hyaluronic acid solutions can be accounted for by their contributions to the ionic strength. Nevertheless, the effects of coiling and self-association can be stimulated in solution by added salt.

  14. Delayed Immune Mediated Adverse Effects to Hyaluronic Acid Fillers: Report of Five Cases and Review of the Literature

    PubMed Central

    Bitterman-Deutsch, Ora; Kogan, Leonid; Nasser, Faris

    2015-01-01

    Hyaluronic acid (HA) fillers in cosmetic medicine have been considered relatively safe, though fillers used in European countries and throughout the world are not necessarily approved by the Food and Drug Administration. As their use continues to expand worldwide, physicians in a wide range of medical specialties are authorized to perform HA injections, including general medicine practitioners and even dentists. An increasing number of reports have appeared regarding side effects to these products. It is now known that reactions to Hyaluronic acid are related not only to technical faults of the injections, but also to immune responses, including delayed hypersensitivity and granulomatous reactions. Herein, we describe five cases treated by a variety of treatment modalities, all with delayed reactions to different brands of hyaluronic acid fillers. As there is currently no standardization of treatment options of adverse effects, these cases accentuate the debate regarding the approach to the individual patient and the possible need for pre-testing in patients with an atopic tendency. PMID:25918619

  15. Biointerface properties of core-shell poly(vinyl alcohol)-hyaluronic acid microgels based on chemoselective chemistry.

    PubMed

    Kupal, Sidhendra G; Cerroni, Barbara; Ghugare, Shivkumar V; Chiessi, Ester; Paradossi, Gaio

    2012-11-12

    Chemoselective chemistry is one of the main synthetic strategies for the design of bioactive constructs. In this contribution we report on the fabrication of core-shell microgel particles, obtained by "click chemistry" and "inverse emulsion droplets" techniques. Azido and alkyne derivatives of poly(vinyl alcohol) (PVA) in a 1:2 mol ratio of functional groups, respectively, were crosslinked by click chemistry method. The microgel particles were spherical in shape with an average diameter of about 2 μm and with a narrow size distribution. Residual unreacted alkyne groups present on the particle surface were "clicked" with an azido-grafted hyaluronic acid. These microgel particles with a PVA core and a hyaluronic acid shell were tested for bioorthogonality, that is, for the absence of cytotoxicity in the presence of unreacted clickable functionalities and demonstrated a remarkable ability to target adenocarcinoma colon cells (HT- 29) as well as to release locally the antitumor drug, doxorubicin. Internalization process was studied in connection with the presence of hyaluronic acid on the microgel particles surface. In this paper we introduce a concept device based on chemoselective chemistry, which may contribute to the design of micro- and nanoplatforms having controlled and multifunctional structures. PMID:23082791

  16. Can combined use of low-level lasers and hyaluronic acid injections prolong the longevity of degenerative knee joints?

    PubMed Central

    Ip, David; Fu, Nga Yue

    2015-01-01

    Background This study evaluated whether half-yearly hyaluronic acid injection together with low-level laser therapy in addition to standard conventional physical therapy can successfully postpone the need for joint replacement surgery in elderly patients with bilateral symptomatic tricompartmental knee arthritis. Methods In this prospective, double-blind, placebo-controlled study, 70 consecutive unselected elderly patients with bilateral tricompartmental knee arthritis were assigned at random to either one of two conservative treatment protocols to either one of the painful knees. Protocol A consisted of conventional physical therapy plus a sham light source plus saline injection, and protocol B consisted of protocol A with addition of half-yearly hyaluronic acid injection as well as low-level laser treatment instead of using saline and a sham light source. Treatment failure was defined as breakthrough pain necessitating joint replacement. Results Among the 140 painful knees treated with either protocol A or protocol B, only one of the 70 painful knees treated by protocol B required joint replacement, whereas 15 of the 70 painful knees treated by protocol A needed joint replacement surgery (P<0.05). Conclusion We conclude that half-yearly hyaluronic acid injections together with low-level laser therapy should be incorporated into the standard conservative treatment protocol for symptomatic knee arthritis, because it may prolong the longevity of the knee joint without the need for joint replacement. PMID:26346122

  17. Chitosan-hyaluronic acid polyelectrolyte complex scaffold crosslinked with genipin for immobilization and controlled release of BMP-2.

    PubMed

    Nath, Subrata Deb; Abueva, Celine; Kim, Boram; Lee, Byong Taek

    2015-01-22

    Polyelectrolyte complex (PEC) is formed when polymers with opposite charges are combined in solution. PECs are recently gaining attention as carriers for controlled release of drugs and proteins. Herein, bone morphogenetic protein-2 (BMP-2) was immobilized in a PEC of natural polymers, chitosan and hyaluronic acid. Charge-to-charge stoichiometry of the formed PEC was estimated based on turbidity of combined chitosan and hyaluronic acid solutions. Free amino groups in chitosan were crosslinked with different amounts of genipin. The degree of crosslinking, consequently its effects in vitro in terms of swelling, degradation and cytocompatibility were analyzed. Immobilization of three different amount of BMP-2 in chitosan-hyaluronic acid PEC scaffold resulted sustained release of the growth factor for more than 30 days. Immobilization efficacies varied from 61% to 76% depending on the amount of BMP-2. Finally effects in osteogenic differentiation of the PEC with BMP-2 to MC3T3-E1 cells were determined by reverse transcriptase PCR. PMID:25439881

  18. 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

  19. Solution structure of hyaluronic acid oligomers by experimental and theoretical NMR, and molecular dynamics simulation.

    PubMed

    Donati, A; Magnani, A; Bonechi, C; Barbucci, R; Rossi, C

    2001-11-01

    The conformational properties of hyaluronic acid (HA) oligomers in aqueous solution were investigated by combining high-resolution NMR experimental results, theoretical simulation of NMR two-dimensional (2D) spectra by Complete Relaxation Matrix Analysis (CORMA), and molecular dynamics calculations. New experimental findings recorded for the tetra- and hexasaccharides enabled the stiffness of the HA and its viscoelastic properties to be interpreted. In particular, rotating frame nuclear Overhauser effect spectroscopy spectra provided new information about the arrangement of the glycosidic linkage. From (13)C NMR relaxation the rotational correlation time (tau(c)) were determined. The tau(c) were employed in the calculation of geometrical constraints, by using the MARDIGRAS algorithm. Restrained simulated annealing and 1 ns of unrestrained molecular dynamic simulations were performed on the hexasaccharide in a box of 1215 water molecules. The beta(1 --> 3) and beta(1 --> 4) glycosidic links were found to be rigid. The lack of rotational degree of freedom is due to direct and/or water-mediated interresidue hydrogen bonding. Both single or tandem water bridges were found between carboxylate group and N-acetil group. The carboxylate group of glucuronic acid is not involved in a direct link with the amide group of N-acetyl glucosamine and this facilitated bonding between the residue and the water molecules. PMID:11598878

  20. 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. PMID:26554699

  1. Biological hydrogel synthesized from hyaluronic acid, gelatin and chondroitin sulfate by click chemistry.

    PubMed

    Hu, Xiaohong; Li, Dan; Zhou, Feng; Gao, Changyou

    2011-04-01

    In order to mimic the natural cartilage extracellular matrix, which is composed of core proteins and glycosaminoglycans, a biological hydrogel was synthesized from the biopolymers hyaluronic acid (HA), chondroitin sulfate (CS) and gelatin via click chemistry. HA and CS were modified with 11-azido-3,6,9-trioxaundecan-1-amine (AA) and gelatin was modified with propiolic acid (PA). The molecular structures were verified by (1)H nuclear magnetic resonance, infrared spectroscopy and elemental analysis, giving substitution degrees of 29%, 89% and 44% for HA-AA, CS-AA and gelatin-PA (G-PA), respectively. The -N(3) groups of HA-AA and CS-AA were reacted with the acetylene groups of G-PA, catalyzed by Cu(I), to form triazole rings, thereby forming a cross-linked hydrogel. The gelation time was decreased monotonically with increasing Cu(I) concentration up to 0.95 mg ml(-1). The hydrogel obtained was in a highly swollen state and showed the characteristics of an elastomer. Incubation in phosphate-buffered saline for 4 weeks resulted in a weight loss of up to 45%. Moreover, about 20% gelatin and 10% CS were released from the hydrogel in 2 weeks. In vitro cell culture showed that the hydrogel could support the adhesion and proliferation of chondrocytes. PMID:21145437

  2. 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. PMID:26874284

  3. Control of the molecular degradation of hyaluronic acid hydrogels for tissue augmentation.

    PubMed

    Oh, Eun Ju; Kang, Sun-Woong; Kim, Byung-Soo; Jiang, Ge; Cho, Il Hwan; Hahn, Sei Kwang

    2008-09-01

    A novel protocol to control the molecular degradation of hyaluronic acid (HA) hydrogels was successfully developed for tissue augmentation applications. HA has a different conformational structure in water and organic solvent, and the carboxyl group of HA is known to be the recognition site of hyaluronidase and HA receptors. Based on these findings, HA was chemically modified by grafting adipic acid dihydrazide (ADH) to the carboxyl group of HA in the water to prepare HA-ADH(WATER) and in the mixed solvent of water and ethanol to prepare degradation-controlled HA-ADH(WATER/ETHANOL). Three kinds of HA hydrogels were prepared by the crosslinking of HA-ADH(WATER) or HA-ADH(WATER/ETHANOL) with bis(sulfosuccinimidyl) suberate, and by the crosslinking of HA-OH with divinyl sulfone (DVS). In vitro and in vivo degradation tests showed that HA-DVS hydrogels were degraded most rapidly, followed by HA-ADH(WATER) hydrogels and HA-ADH(WATER/ETHANOL) hydrogels. There was no adverse effect during and after in vivo degradation tests. All of the HA hydrogel samples appeared to be biocompatible, according to the histological analysis with hematoxylin-eosin and Alcian blue. PMID:18022803

  4. Biodistribution profiling of the chemical modified hyaluronic acid derivatives used for oral delivery system.

    PubMed

    Hsieh, Chien-Ming; Huang, Yu-Wen; Sheu, Ming-Thau; Ho, Hsiu-O

    2014-03-01

    A series of adipic acid dihydrazide (ADH)-modified hyaluronic acid (HA-ADH) compounds were synthesized and conjugated with QDots (QDots-HA conjugates) to assess the effects of the molecular weight (MW) and extent of chemical modification of HA on its biodistribution. Their physicochemical structures were confirmed by complementary application of GPC, (1)H NMR, FTIR, and UV-vis spectroscopic methods. In vivo imaging of QDots-HA conjugates after oral administration was analyzed to investigate their biodistribution in nude mice. Simultaneously, real-time bioimaging was confirmed by an anatomical analysis to investigate the organ-specific accumulation of conjugates. QDot-HA conjugates with a higher MW of HA or high modification presented relatively slow clearance leading to an extension of the retention time for up to 10 days, whereas those with lower MWs of HA or a low modification extent exhibited quick absorption and elimination after oral administration. Taken together, HA derivatives with suitable MWs and chemical modification extents can be used to design new, more-sophisticated, and intelligent HA-based vehicles for oral delivery with diverse characteristics. PMID:24315950

  5. Sustained release formulation of erythropoietin using hyaluronic acid hydrogels crosslinked by Michael addition.

    PubMed

    Hahn, Sei Kwang; Oh, Eun Ju; Miyamoto, Hajime; Shimobouji, Tsuyoshi

    2006-09-28

    A novel sustained release formulation of erythropoietin (EPO) was successfully developed using hyaluronic acid (HA) hydrogels crosslinked by Michael addition. Adipic acid dihydrazide grafted HA (HA-ADH) was prepared and then modified into methacrylated HA (HA-MA). (1)H NMR analysis showed that the degrees of HA-ADH and HA-MA modification were 69 and 29 mol%, respectively. Using the specific crosslinkers of dithiothreitol (DTT) and peptide linker, EPO was loaded during HA-MA hydrogel preparation by Michael addition chemistry between thiol and methacrylate groups. The amount of EPO recovered from both hydrogels after degradation with hyaluronidase SD (HAse SD) was about 90%. The crosslinking reaction with peptide linker (GCYKNRDCG) was faster than that with DTT. The gelation time was about 30 min for peptide linker and 180 min for DTT. In vitro release test of EPO from HA-MA hydrogel at 37 degrees C showed that EPO was released rapidly for 2 days and then slowly up to 7 days from HA-MA hydrogels. The released EPO appeared to be intact from the analysis with RP-HPLC. According to in vivo release test of EPO from HA-MA hydrogels crosslinked with the peptide linker in Sprague-Dawley (SD) rats, elevated plasma concentration of EPO was maintained up to 7 days. There was no adverse effect during and after the in vivo tests. PMID:16781096

  6. Interconnected hyaluronic acid derivative-based nanoparticles for anticancer drug delivery.

    PubMed

    Park, Ju-Hwan; Cho, Hyun-Jong; Termsarasab, Ubonvan; Lee, Jae-Young; Ko, Seung-Hak; Shim, Jae-Seong; Yoon, In-Soo; Kim, Dae-Duk

    2014-09-01

    Doxorubicin (DOX)-loaded nanoparticles (NPs) based on interconnected hyaluronic acid-ceramide (HACE) structure were fabricated and their anti-tumor efficacy was evaluated in vitro. Interconnected HACE was synthesized by cross-linking HACE with adipic acid dihydrazide (ADH) and its synthesis was identified by (1)H NMR analysis. DOX-loaded NPs with <200nm mean diameter, negative zeta potential, and spherical shape were prepared. Interconnected HACE-based NPs increased drug-loading capacity and in vitro drug release, compared to HACE-based NPs. DOX release was dependent on the environmental pH, implying the feasibility of enhancing drug release in tumor region and endosomal compartments. Synthesized interconnected HACE did not show cytotoxic effect up to 1000μg/ml concentration in NIH3T3 and MDA-MB-231 cells. In cellular uptake studies using confocal laser scanning microscopy (CLSM) and flow cytometry in MDA-MB-231 cells, higher uptake of DOX was observed in the interconnected HACE-based NPs than HACE NPs. In vitro anti-tumor efficacy was assessed by MTS-based assay, in which cytotoxic effect of DOX-loaded interconnected HACE NPs was higher than that of DOX-loaded HACE NPs. Thus, these results suggest the feasibility of interconnected HACE-based NPs to be used for efficient tumor-targeted delivery of anticancer drugs. PMID:24993066

  7. 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. PMID:26893053

  8. pH-responsive targeted and controlled doxorubicin delivery using hyaluronic acid nanocarriers.

    PubMed

    Gurav, Deepanjali D; Kulkarni, Anuja S; Khan, Ayesha; Shinde, Vaishali S

    2016-07-01

    Biocompatible nanogels were prepared using thiol modified hyaluronic acid and diacrylated pluronic F127 polymer. A simple Michael type addition reaction of activated thiol groups on acrylate moiety lead to the formation of these nanogels, which were further effectively fabricated with an anticancer drug for evaluating sustained drug release approach. Nanogels prepared were of 150nm in diameter with a narrow size distribution pattern. DOX released from these nanogels showed a slow and sustained release at acidic pH 5.0 as compared to minimal release at physiological pH 7.4. Cytotoxicity data revealed the higher efficiency of DOX loaded nanogels as compared to free DOX in Hela cell lines. Cellular uptake images supported the cytotoxicity data and displayed DOX intercalation at nuclear level of cells. The sustained drug delivery system showed DOX release after 24h and continued thereafter without affecting normal cells. Based on these findings, such nanogel system may be useful for delivering anticancer drug without hampering their toxicity value over longer durations and reducing the total dose amount in anticancer therapy. PMID:27022876

  9. 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.

  10. 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. PMID:26876867