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Sample records for hyaluronic acid binding

  1. 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

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

    PubMed

    Torabi, Forough; Binduraihem, Adel; Miller, David

    2017-03-01

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

  3. 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.

  4. 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.

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

    PubMed

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

    2014-10-01

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

  6. Protein binding assay for hyaluronate

    SciTech Connect

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

    1986-11-01

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

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

    SciTech Connect

    McGary, C.T.

    1988-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. 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

  10. Beneficial effects of hyaluronic acid.

    PubMed

    Sudha, Prasad N; Rose, Maximas H

    2014-01-01

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

  11. Hyaluronic Acid Binding Sperm Selection for assisted reproduction treatment (HABSelect): study protocol for a multicentre randomised controlled trial

    PubMed Central

    Witt, K D; Beresford, L; Bhattacharya, S; Brian, K; Coomarasamy, A; Hooper, R; Kirkman-Brown, J; Khalaf, Y; Lewis, S E; Pacey, A; Pavitt, S; West, R

    2016-01-01

    Introduction The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial is to determine the efficacy of hyaluronic acid (HA)-selection of sperm versus conventionally selected sperm prior to ICSI on live birth rate (LBR). The mechanistic aim is to assess whether and how the chromatin state of HA-selected sperm corresponds with clinical outcomes—clinical pregnancy rate (CPR), LBR and pregnancy loss (PL). Methods and analysis Couples attending UK Centres will be approached, eligibility screening performed and informed consent sought. Randomisation will occur within 24 hours prior to ICSI treatment. Participants will be randomly allocated 1:1 to the intervention arm (physiological intracytoplasmic sperm injection, PICSI) versus the control arm using conventional methods (ICSI). The primary clinical outcome is LBR ≥37 weeks' gestation with the mechanistic study determining LBR's relationship with sperm DNA integrity. Secondary outcomes will determine this for CPR and PL. Only embryologists performing the procedure will be aware of the treatment allocation. Steps will be taken to militate against biases arising from embryologists being non-blinded. Randomisation will use a minimisation algorithm to balance for key prognostic variables. The trial is powered to detect a 5% difference (24–29%: p=0.05) in LBR ≥37 weeks' gestation. Selected residual sperm samples will be tested by one or more assays of DNA integrity. Ethics and dissemination HABSelect is a UK NIHR-EME funded study (reg no 11/14/34; IRAS REF. 13/YH/0162). The trial was designed in partnership with patient and public involvement to help maximise patient benefits. Trial findings will be

  12. 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

  13. No difference in high-magnification morphology and hyaluronic acid binding in the selection of euploid spermatozoa with intact DNA

    PubMed Central

    Mongkolchaipak, Suchada; Vutyavanich, Teraporn

    2013-01-01

    In this study, we compared conventional sperm selection with high-magnification morphology based on the motile sperm organellar morphology examination (MSOME) criteria, and hyaluronic acid (HA) binding for sperm chromosome aneuploidy and DNA fragmentation rates. Semen from 50 severe male factor cases was processed through density gradient centrifugation, and subjected to sperm selection by using the conventional method (control), high magnification at ×6650 or HA binding. Aneuploidy was detected by fluorescence in situ hybridization with probes for chromosomes 13, 18, 21, X and Y, and DNA fragmentation by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) method. Spermatozoa selected under high-magnification had a lower DNA fragmentation rate (2.6% vs. 1.7% P=0.032), with no significant difference in aneuploidy rate (0.8% vs 0.7% P=0.583), than those selected by the HA binding method. Spermatozoa selected by both methods had much lower aneuploidy and DNA fragmentation rate than the controls (7% aneuploidy and 26.8% DNA fragmentation rates, respectively). In the high-magnification group, the aneuploidy rate was lower when the best spermatozoa were selected than when only the second-best spermatozoa were available for selection, but the DNA fragmentation rate was not different. In conclusion, sperm selection under high magnification was more effective than under HA binding in selecting spermatozoa with low DNA fragmentation rate, but the small difference (0.9%) might not be clinically meaningful. Both methods were better than the conventional method of sperm selection. PMID:23435468

  14. No difference in high-magnification morphology and hyaluronic acid binding in the selection of euploid spermatozoa with intact DNA.

    PubMed

    Mongkolchaipak, Suchada; Vutyavanich, Teraporn

    2013-05-01

    In this study, we compared conventional sperm selection with high-magnification morphology based on the motile sperm organellar morphology examination (MSOME) criteria, and hyaluronic acid (HA) binding for sperm chromosome aneuploidy and DNA fragmentation rates. Semen from 50 severe male factor cases was processed through density gradient centrifugation, and subjected to sperm selection by using the conventional method (control), high magnification at ×6650 or HA binding. Aneuploidy was detected by fluorescence in situ hybridization with probes for chromosomes 13, 18, 21, X and Y, and DNA fragmentation by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) method. Spermatozoa selected under high-magnification had a lower DNA fragmentation rate (2.6% vs. 1.7%; P=0.032), with no significant difference in aneuploidy rate (0.8% vs 0.7%; P=0.583), than those selected by the HA binding method. Spermatozoa selected by both methods had much lower aneuploidy and DNA fragmentation rate than the controls (7% aneuploidy and 26.8% DNA fragmentation rates, respectively). In the high-magnification group, the aneuploidy rate was lower when the best spermatozoa were selected than when only the second-best spermatozoa were available for selection, but the DNA fragmentation rate was not different. In conclusion, sperm selection under high magnification was more effective than under HA binding in selecting spermatozoa with low DNA fragmentation rate, but the small difference (0.9%) might not be clinically meaningful. Both methods were better than the conventional method of sperm selection.

  15. The Pattern of Tyrosine Phosphorylation in Human Sperm in Response to Binding to Zona Pellucida or Hyaluronic Acid

    PubMed Central

    Sati, Leyla; Cayli, Sevil; Delpiano, Elena; Sakkas, Denny

    2014-01-01

    In mammalian species, acquisition of sperm fertilization competence is dependent on the phenomenon of sperm capacitation. One of the key elements of capacitation is protein tyrosine phosphorylation (TP) in various sperm membrane regions. In previous studies performed, the pattern of TP was examined in human sperm bound to zona pellucida of oocytes. In the present comparative study, TP patterns upon sperm binding to the zona pellucida or hyaluronic acid (HA) were investigated in spermatozoa arising from the same semen samples. Tyrosine phosphorylation, visualized by immunofluorescence, was localized within the acrosomal cap, equatorial head region, neck, and the principal piece. Tyrosine phosphorylation has increased in a time-related manner as capacitation progressed, and the phosphorylation pattern was identical within the principal piece and neck, regardless of the sperm bound to the zona pellucida or HA. Thus, the data demonstrated that the patterns of sperm activation-related TP were similar regardless of the spermatozoa bound to zona pellucida or HA. Further, sperm with incomplete development, as detected by excess cytoplasmic retention, failed to exhibit TP. PMID:24077441

  16. Characterization of an intracellular hyaluronic acid binding site in isolated rat hepatocytes

    SciTech Connect

    Frost, S.J.; Raja, R.H.; Weigel, P.H. )

    1990-11-13

    125I-HA, prepared by chemical modification at the reducing sugar, specifically binds to rat hepatocytes in suspension or culture. Intact hepatocytes have relatively few surface 125I-HA binding sites and show low specific binding. However, permeabilization of hepatocytes with the nonionic detergent digitonin results in increased specific 125I-HA binding (45-65%) and a very large increase in the number of specific 125I-HA binding sites. Scatchard analysis of equilibrium 125I-HA binding to permeabilized hepatocytes in suspension at 4 degrees C indicates a Kd = 1.8 x 10(-7) M and 1.3 x 10(6) molecules of HA (Mr approximately 30,000) bound per cell at saturation. Hepatocytes in primary culture for 24 h show the same affinity but the total number of HA molecules bound per cell at saturation decreases to approximately 6.2 x 10(5). Increasing the ionic strength above physiologic concentrations decreases 125I-HA binding to permeable cells, whereas decreasing the ionic strength above causes an approximately 4-fold increase. The divalent cation chelator EGTA does not prevent binding nor does it release 125I-HA bound in the presence of 2 mM CaCl2, although higher divalent cation concentrations stimulate 125I-HA binding. Ten millimolar CaCl2 or MnCl2 increases HA binding 3-6-fold compared to EGTA-treated cells. Ten millimolar MgCl2, SrCl2, or BaCl2 increased HA binding by 2-fold. The specific binding of 125I-HA to digitonin-treated hepatocytes at 4{degrees}C increased greater than 10-fold at pH 5.0 as compared to pH 7.

  17. [Injection treatment with hyaluronic acid].

    PubMed

    Jerosch, J

    2015-11-01

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

  18. Surface-tension properties of hyaluronic Acid.

    PubMed

    Knepper, P A; Covici, S; Fadel, J R; Mayanil, C S; Ritch, R

    1995-06-01

    The maintenance of flow channels in the trabecular meshwork is dependent, in part, on the patency of the trabecular spaces. Because the amount of hyaluronic acid decreases in the trabecular meshwork of patients with primary open-angle glaucoma, a change in surface tension may be one of the effects of hyaluronic acid on aqueous outflow. The surface-active properties of hyaluronic acid (concentration of 0.156-2.5 mg/ml; molecular weights of 100,000, 500,000, and 4,000,000) in deionized water, Ringer's lactate, Ringer's lactate plus 0.06 mg/ml bovine serum albumin, and mock aqueous solution were tested using the drop volume method. At a hyaluronic acid concentration of 0.312 mg/ml, surface tension decreased; at higher concentrations, a further decrease in surface tension was observed. In the presence of Ringer's lactate, the 100,000-MW hyaluronic acid was more active than the 4,000,000-MW hyaluronic acid. In the presence of Ringer's lactate plus bovine serum albumin or mock aqueous solution, the influence of surface tension of the 100,000-MW hyaluronic acid was moderated: with lower hyaluronic acid concentrations, the decline in surface tension was more than with Ringer's lactate, but with higher hyaluronic acid concentrations, the decline in surface tension was less than with Ringer's lactate. At high concentration, hyaluronic acid behaves like a non-Newtonian fluid, becomes more viscous, and may act to "seal" the trabecular space. The results of this study indicate that hyaluronic acid possesses surface-active properties, which is just one of several properties of hyaluronic acid that may influence aqueous outflow resistance.

  19. Hyaluronic acid concentration in liver diseases.

    PubMed

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

    2016-11-01

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

  20. Chemical Synthesis of Modified Hyaluronic Acid Disaccharides.

    PubMed

    Mende, Marco; Nieger, Martin; Bräse, Stefan

    2017-09-07

    Herein we report a chemical synthesis towards new modified hyaluronic acid oligomers by using only commercially available d-glucose and d-glucosamine hydrochloride. The various protected hyaluronic acid disaccharides were synthesized bearing new functional groups at C-6 of the β-d-glucuronic acid moiety with a view to structure-related biological activity tests. The orthogonal protecting group pattern allows ready access to the corresponding higher oligomers. Also, (1) H NMR studies of the new derivatives demonstrated the effect of the various functional groups on the intramolecular electronic environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Characterization of hyaluronate binding proteins isolated from 3T3 and murine sarcoma virus transformed 3T3 cells

    SciTech Connect

    Turley, E.A.; Moore, D.; Hayden, L.J.

    1987-06-02

    A hyaluronic acid binding fraction was purified from the supernatant media of both 3T3 and murine sarcoma virus (MSV) transformed 3T3 cultures by hyaluronate and immunoaffinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the hyaluronate affinity-purified fraction into three major protein bands of estimated molecular weight (M/sub r,e/) 70K, 66K, and 56K which contained hyaluronate binding activity and which were termed hyaluronate binding proteins (HABP). Hyaluronate affinity chromatography combined with immunoaffinity chromatography, using antibody directed against the larger HABP, allowed a 20-fold purification of HABP. Fractions isolated from 3T3 supernatant medium also contained additional binding molecules in the molecular weight range of 20K. This material was present in vanishingly small amounts and was not detected with a silver stain or with (/sup 35/S)methionine label. The three protein species isolated by hyaluronate affinity chromatography (M/sub r,e/ 70K, 66K, and 56K) were related to one another since they shared antigenic determinants and exhibited similar pI values. In isocratic conditions, HABP occurred as aggregates of up to 580 kilodaltons. Their glycoprotein nature was indicated by their incorporation of /sup 3/H-sugars. Enzyme-linked immunoadsorbent assay showed they were antigenically distinct from other hyaluronate binding proteins such as fibronectin, cartilage link protein, and the hyaluronate binding region of chondroitin sulfate proteoglycan. The results are discussed with regard both to the functional significance of hyaluronate-cell surface interactions in transformed as well as normal cells and to the relationship of HABP to other reported hyaluronate binding proteins.

  2. 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

  3. Dietary Hyaluronic Acid Migrates into the Skin of Rats

    PubMed Central

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

    2014-01-01

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

  4. [Serum hyaluronic acid in osteoarthritis].

    PubMed

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

    1993-03-01

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

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

    PubMed

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

    2015-01-01

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

  6. 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. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2014-10-01

    Complex coacervates of hyaluronic acid and lysozyme, a model protein, were formed by ionic interaction using bulk mixing and were characterized in terms of binding stoichiometry and protein structure and stability. The complexes were formed at pH 7.2 at low ionic strength (6mM) and the binding stoichiometry was determined using solution depletion and isothermal titration calorimetry. The binding stoichiometry of lysozyme to hyaluronic acid (870 kDa) determined by solution depletion was found to be 225.9 ± 6.6 mol, or 0.1 bound lysozyme molecules per hyaluronic acid monomer. This corresponded well with that obtained by isothermal titration calorimetry of 0.09 bound lysozyme molecules per hyaluronic acid monomer. The complexation did not alter the secondary structure of lysozyme measured by Fourier-transform infrared spectroscopy overlap analysis and had no significant impact on the Tm of lysozyme determined by differential scanning calorimetry. Furthermore, the protein stability of lysozyme was found to be improved upon complexation during a 12-weeks storage study at room temperature, as shown by a significant increase in recovered protein when complexed (94 ± 2% and 102 ± 5% depending on the polymer-protein weight to weight ratio) compared to 89 ± 2% recovery for uncomplexed protein. This study shows the potential of hyaluronic acid to be used in combination with complex coacervation to increase the physical stability of pharmaceutical protein formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-11-01

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

  9. 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.

  10. Hyaluronic acid production by recombinant Lactococcus lactis.

    PubMed

    Chien, Liang-Jung; Lee, Cheng-Kang

    2007-11-01

    Microbial hyaluronic acid (HA), commonly produced by pathogenic Streptococcus, was made possible to be produced by a generally recognized as safe Lactococcus lactis by coexpressing HA synthase and uridine diphosphate-glucose dehydrogenase (UDP-GlcDH) of Streptococcus equi subsp. zooepidemicus in a nisin-controlled expression (NICE) system. With scarce expressed HA synthase alone, the constructed recombinant L. lactis (LL-NA) strain could produce HA with a concentration about 0.08 g/l in the M17 medium supplemented with 1% (w/v) glucose. In contrast to HA synthase, UDP-GlcDH of Streptococcus could be overexpressed in the NICE system. With coexpression of heterologous UDP-GlcDH with HA synthase, the constructed LL-NAB strain grew slightly slower to a concentration about 10% lower that of the LL-NA strain. However, the HA concentration produced was enhanced about eightfold to 0.65 g/l.

  11. Intra-articular hyaluronic acid injection: not for gonarthrosis.

    PubMed

    2013-10-01

    A meta-analysis of 89 randomised trials suggests that, at best, intraarticular hyaluronic acid injection only provides a small relief to patients with osteoarthritis of the knee, but that it can provoke both local reactions and serious adverse effects.

  12. 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.

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

    PubMed

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

    2009-08-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

    Riehl, Terrence E.; Santhanam, Srikanth; Foster, Lynne; Ciorba, Matthew

    2015-01-01

    Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3–8 wk of age to wild-type, CD44−/−, and TLR4−/− mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5+ stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5+ reporter mice from postnatal day 7 to day 14 decreased Lgr5+ cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5+ stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4. PMID:26505972

  16. 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.

  17. 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.

  18. Physical properties of crosslinked hyaluronic acid hydrogels.

    PubMed

    Collins, Maurice N; Birkinshaw, Colin

    2008-11-01

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

  19. 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

  20. Biocompatible, hyaluronic acid modified silicone elastomers.

    PubMed

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

    2010-05-01

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

  1. 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.

  2. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. 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.

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

    PubMed

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

    2015-01-15

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    1983-01-01

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

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

    PubMed

    Tsepilov, R N; Beloded, A V

    2015-09-01

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

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

    PubMed

    Wu, Yue

    2012-06-20

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

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

    PubMed

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

    2013-03-01

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

  10. Hyaluronic acid: Hope of light to black triangles

    PubMed Central

    Tanwar, Jyotsana; Hungund, Shital A.

    2016-01-01

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

  11. Hyaluronate lyase activity of Streptococcus suis serotype 2 and modulatory effects of hyaluronic acid on the bacterium's virulence properties.

    PubMed

    Haas, Bruno; Vaillancourt, Katy; Bonifait, Laetitia; Gottschalk, Marcelo; Grenier, Daniel

    2015-11-26

    Streptococcus suis serotype 2 is a major swine pathogen and zoonotic agent worldwide causing mainly meningitis and septicemia. Hyaluronate lyases are enzymes that degrade hyaluronic acid, a major constituent of animal tissues, and have been reported as virulence factors in various bacterial species. Since the hyaluronate lyase of S. suis has been considered ambiguously as a virulence factor, we screened 50 isolates from the three major clonal complexes found in North America (sequence type [ST] 1, ST25, and ST28) known to differ in their degree of virulence in order to link the presence or absence of this activity with the degree of virulence. Moreover, the effect of exogenous hyaluronic acid on S. suis virulence factor gene expression and the pro-inflammatory response of brain macrovascular endothelial cells (BMEC) was also investigated. We found that all but one ST1 isolates (high virulence) were devoid of hyaluronate lyase activity whereas all ST25 (intermediate virulence) and ST28 (low virulence) isolates possessed the activity. A 2 bp insertion was responsible for the lack of activity in ST1 strains. Since the most virulent isolates did not degrade hyaluronic acid, this tissue component may be found during the infectious process. Therefore, we investigated its effect on S. suis and host cells. Hyaluronic acid was found to modulate S. suis adhesion to BMEC, to increase S. suis virulence factor expression, and to enhance pro-inflammatory cytokine secretion by BMEC. These findings suggest that S. suis hyaluronate lyase does not represent a critical virulence factor in its active form. However, exogenous hyaluronic acid that is likely to interact with S. suis and host cells during the course of infection appears to modulate several virulence determinants of the bacterium, in addition to promote inflammation.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

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

    PubMed

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

    2015-04-01

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

  15. Use of hyaluronic Acid gel in the management of paralytic lagophthalmos: the hyaluronic Acid gel "gold weight".

    PubMed

    Mancini, Ronald; Taban, Mehryar; Lowinger, Alan; Nakra, Tanuj; Tsirbas, Angelo; Douglas, Raymond S; Shorr, Norman; Goldberg, Robert A

    2009-01-01

    To evaluate the safety and efficacy of injecting hyaluronic acid gel in the upper eyelid as a nonsurgical alternative in the treatment of paralytic lagophthalmos. This is a retrospective study of 9 patients (10 eyelids) with paralytic lagophthalmos treated with hyaluronic acid gel in the prelevator aponeurosis region and/or pretarsal region of the paralytic upper eyelid. Pretreatment, posttreatment, and follow-up photographs were digitized, and overall outcomes assessed. Measurements of lagophthalmos were standardized and compared. Slit-lamp examination was used to evaluate the degree of exposure keratopathy. ImageJ was used for photographic analysis. Ten eyelids (9 patients, 7 men; mean age 69.2 years; range, 31-90 years) with paralytic lagophthalmos were treated with hyaluronic acid gel. The average amount of injected hyaluronic acid gel was 0.9 ml (range, 0.2-1.2 ml). All patients demonstrated significant improvement in lagophthalmos and exposure keratopathy. The mean improvement in lagophthalmos was 4.8 mm (range, 0.9-11.9 mm; p = 0.001). Of the 5 patients with follow-up, the mean follow-up period was 3.6 months (range, 2-5 months). Of these, 2 had no change in lagophthalmos (both maintained 0 mm at 5 months), one had a slight decrease in lagophthalmos (4.8-4.6 mm at 2 months), one had a slight increase in lagophthalmos (0.3-0.5 mm at 2 months), and one had a more significant increase in lagophthalmos (1.9-4.3 mm at 4 months). The latter patient underwent a second treatment with further reduction of lagophthalmos to 0.4 mm. Overall, there was a decrease in margin reflex distance from the upper eyelid margin to the corneal light reflex (MRD1) but it was not statistically significant. Complications were minor and included transient ecchymosis, edema, and tenderness at the injection sites. On the basis of these preliminary results, hyaluronic acid gel shows promise as a safe and effective nonsurgical treatment for the management of paralytic lagophthalmos. This

  16. 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.

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

    PubMed

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

    2014-10-01

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

  18. 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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  1. Labia Majora Augmentation with Hyaluronic Acid Filler: Technique and Results.

    PubMed

    Fasola, Elena; Gazzola, Riccardo

    2016-11-01

    External female genitalia lose elasticity and volume with age. In the literature several techniques address the redundancy of the labia minora, but only few reports describe the augmentation of labia majora with fat grafting. At present, no studies describe the augmentation of the labia majora with hyaluronic acid. This study aims to present our technique of infiltration of hyaluronic acid filler, analyzing effectiveness, patient satisfaction, and complications. We retrospectively analyzed 54 patients affected by hypotrophy of the labia majora; they were treated with hyaluronic acid filler between November 2010 and December 2014. The Global Aesthetic Improvement Scale (GAIS) filled out by the doctor and the patients was used to evaluate the results 12 months after the infiltration. Complications were recorded. A total of 31 patients affected by mild to moderate labia majora hypotrophy were treated with 19 mg/mL HA filler; 23 patients affected by severe labia majora hypotrophy were treated with 21 mg/mL HA filler. Among the first group of patients, one underwent a second infiltration 6 months later with 19 mg/mL HA filler (maximum 1 mL). A significant improvement (P < .0001) in GAIS score was observed, both in the scores provided by the patients and by the doctor. A greater relative improvement was observed in patients affected by severe hypotrophy. No complications were recorded. Hyaluronic acid infiltration of the labia majora is able to provide a significant rejuvenation with a simple outpatient procedure. We achieved significant improvements with one infiltration in all cases. The treatment is repeatable, has virtually no complications and it is reversible. 4 Therapeutic. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2003-06-05

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

  4. The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule

    PubMed Central

    Mégroz, Marianne; Kleifeld, Oded; Wright, Amy; Powell, David; Harrison, Paul; Adler, Ben; Harper, Marina

    2016-01-01

    The Gram-negative bacterium Pasteurella multocida is the causative agent of a number of economically important animal diseases, including avian fowl cholera. Numerous P. multocida virulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA-binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that a P. multocida hfq mutant produces significantly less hyaluronic acid capsule during all growth phases and displays reduced in vivo fitness. Transcriptional and proteomic analyses of the hfq mutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of the hfq mutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in the hfq mutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression of P. multocida genes, including the regulation of key P. multocida virulence factors, capsule, LPS, and filamentous hemagglutinin. PMID:26883595

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

    PubMed

    Lee, Jin Wook; Kim, Hyung Hun

    2014-03-01

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

  6. The effects of vitamin A compounds on hyaluronic acid released from cultured rabbit corneal epithelial cells and keratocytes.

    PubMed

    Toshida, Hiroshi; Tabuchi, Nobuhito; Koike, Daisuke; Koide, Misao; Sugiyama, Keikichi; Nakayasu, Kiyoo; Kanai, Atsushi; Murakami, Akira

    2012-01-01

    A role of vitamin A in the synthesis of hyaluronic acid by skin cells is well known. Hyaluronic acid is produced by corneal epithelial cells and keratocytes in the eye. We investigated whether rabbit corneal epithelial cells and keratocytes release hyaluronic acid after exposure to vitamin A compounds. Rabbit corneal epithelial cells and keratocytes were inoculated with RCGM2 medium and incubated at 37ºC under 5% CO(2) in air for 24 h. The medium was then replaced with medium containing 0.1, 1, 10, or 100 μM retinoic acid or retinol palmitate (VApal) and incubated for another 48 h. Hyaluronic acid release from both corneal epithelial cells and keratocytes during culture was increased by retinoic acid at the lower concentration of 0.1 μM and 1 μM determined with a sandwich binding protein assay kit. However, it was significantly decreased at the higher concentrations of 10 μM and 100 μM, and the cell count determined with a Neutral Red assay kit was also decreased at these concentrations. On the other hand, hyaluronic acid release from corneal epithelial cells during culture was increased by VApal at the lower concentration of 0.1 μM and 1 μM, but there was no significant difference in the cell count for either corneal epithelial cells or keratocytes in the presence of VApal at any concentration. In conclusion, it is suggested that vitamin A stimulates the release of hyaluronic acid from cultured rabbit corneal epithelial cells and keratocytes.

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

    PubMed

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

    2014-02-01

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

  8. Carbon dioxide therapy and hyaluronic acid for cosmetic correction of the nasolabial folds.

    PubMed

    Nisi, Giuseppe; Cuomo, Roberto; Brandi, Cesare; Grimaldi, Luca; Sisti, Andrea; D'Aniello, Carlo

    2016-06-01

    The main application of hyaluronic acid filling, in esthetic medicine, is the augmentation of soft tissues. The carbon dioxide therapy, instead, improves quality and elasticity of the dermis and increases the oxygen release to the tissue through an enhancing of the Bohr's effect. The aim of the study was to compare the efficacy, tolerability, and effect duration of hyaluronic acid fillers and the use of carbon dioxide therapy plus hyaluronic acid in the cosmetic correction of nasolabial folds. Forty healthy female patients received a blinded and randomized treatment on nasolabial folds (hyaluronic acid in group A and hyaluronic acid plus subcutaneous injections of carbon dioxide in group B) for cosmetic correction of the nasolabial folds. The results were evaluated by two blinded plastic surgeons after the implant (1 week, 4 and 6 months) using a 1-5 graduated scale (GAIS), and at the same time, each patient was asked to express her opinion about the cosmetic result. Any long-term adverse reaction was reported. The blinded evaluation at 4 and 6 months from the implant shows in all patients a maintenance of a good cosmetic result higher for the side treated with carbon dioxide therapy plus hyaluronic acid. At the control visit, 6 months after the treatment, the patients treated with hyaluronic acid plus carbon dioxide therapy maintain a satisfactory esthetic result while the nasolabial fold treated only with hyaluronic acid shows, in almost all patients, a come back to pretreatment appearance. © 2016 Wiley Periodicals, Inc.

  9. Enhanced transdermal lymphatic drug delivery of hyaluronic acid modified transfersomes for tumor metastasis therapy.

    PubMed

    Kong, Ming; Hou, Lin; Wang, Juan; Feng, Chao; Liu, Ya; Cheng, Xiaojie; Chen, Xiguang

    2015-01-28

    A novel hyaluronic acid modified transfersome was prepared to deliver drugs to lymphatics through the transdermal route. Doxorubicin loaded HA-GMS-T was able to efficiently penetrate into the deep skin tissue, leading to enhanced absorption by lymphatics. Most importantly, hyaluronic acid effectively improved the uptake of drug loaded nanocarriers by tumor cells.

  10. 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.

  11. Streptococcus pneumoniae Can Utilize Multiple Sources of Hyaluronic Acid for Growth

    PubMed Central

    Marion, Carolyn; Stewart, Jason M.; Tazi, Mia F.; Burnaugh, Amanda M.; Linke, Caroline M.; Woodiga, Shireen A.

    2012-01-01

    The mechanisms by which Streptococcus pneumoniae obtains carbohydrates for growth during airway colonization remain to be elucidated. The low concentration of free carbohydrates in the normal human airway suggests that pneumococci must utilize complex glycan structures for growth. The glycosaminoglycan hyaluronic acid is present on the apical surface of airway epithelial cells. As pneumococci express a hyaluronate lyase (Hyl) that cleaves hyaluronic acid into disaccharides, we hypothesized that during colonization pneumococci utilize the released carbohydrates for growth. Hyaluronic acid supported significant pneumococcal growth in an hyl-dependent manner. A phosphoenolpyruvate-dependent phosphotransferase system (PTS) and an unsaturated glucuronyl hydrolase (Ugl) encoded downstream of hyl are also essential for growth on hyaluronic acid. This genomic arrangement is present in several other organisms, suggesting conservation of the utilization mechanism between species. In vivo experiments support the hypothesis that S. pneumoniae utilizes hyaluronic acid as a carbon source during colonization. We also demonstrate that pneumococci can utilize the hyaluronic acid capsule of other bacterial species for growth, suggesting an alternative carbohydrate source for pneumococcal growth. Together, these data support a novel function for pneumococcal degradation of hyaluronic acid in vivo and provide mechanistic details of growth on this glycosaminoglycan. PMID:22311922

  12. Streptococcus pneumoniae can utilize multiple sources of hyaluronic acid for growth.

    PubMed

    Marion, Carolyn; Stewart, Jason M; Tazi, Mia F; Burnaugh, Amanda M; Linke, Caroline M; Woodiga, Shireen A; King, Samantha J

    2012-04-01

    The mechanisms by which Streptococcus pneumoniae obtains carbohydrates for growth during airway colonization remain to be elucidated. The low concentration of free carbohydrates in the normal human airway suggests that pneumococci must utilize complex glycan structures for growth. The glycosaminoglycan hyaluronic acid is present on the apical surface of airway epithelial cells. As pneumococci express a hyaluronate lyase (Hyl) that cleaves hyaluronic acid into disaccharides, we hypothesized that during colonization pneumococci utilize the released carbohydrates for growth. Hyaluronic acid supported significant pneumococcal growth in an hyl-dependent manner. A phosphoenolpyruvate-dependent phosphotransferase system (PTS) and an unsaturated glucuronyl hydrolase (Ugl) encoded downstream of hyl are also essential for growth on hyaluronic acid. This genomic arrangement is present in several other organisms, suggesting conservation of the utilization mechanism between species. In vivo experiments support the hypothesis that S. pneumoniae utilizes hyaluronic acid as a carbon source during colonization. We also demonstrate that pneumococci can utilize the hyaluronic acid capsule of other bacterial species for growth, suggesting an alternative carbohydrate source for pneumococcal growth. Together, these data support a novel function for pneumococcal degradation of hyaluronic acid in vivo and provide mechanistic details of growth on this glycosaminoglycan.

  13. 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.

  14. 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.

  15. Photo-crosslinked hyaluronic acid coated upconverting nanoparticles

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  16. Studies on the hyaluronate binding properties of newly synthesized proteoglycans purified from articular chondrocyte cultures

    SciTech Connect

    Sandy, J.D.; Plaas, A.H.

    1989-06-01

    Primary cultures of rabbit articular chondrocytes have been maintained for 10 days and labeled with (35S)sulfate, (3H)leucine, and (35S)cysteine in pulse-chase protocols to study the structure and hyaluronate binding properties of newly synthesized proteoglycan monomers. Radiolabeled monomers were purified from medium and cell-layer fractions by dissociative CsCl gradient centrifugation with bovine carrier monomer, and analyzed for hyaluronate binding affinity on Sepharose CL-2B in 0.5 M Na acetate, 0.1% Triton X-100, pH 6.8. Detergent was necessary to prevent self-association of newly synthesized monomers during chromatography. Monomers secreted during a 30-min pulse labeling with (35S)sulfate had a low affinity relative to carrier. Those molecules released into the medium during the first 12 h of chase remained in the low affinity form whereas those retained by the cell layer rapidly acquired high affinity. In cultures where more than 90% of the preformed cell-layer proteoglycan was removed by hyaluronidase digestion before radiolabeling the newly synthesized low affinity monomers also rapidly acquired high affinity if retained in the cell layer. Cultures labeled with amino acid precursors were used to establish the purity of monomer preparations and to isolate core proteins for study. Leucine- or cysteine-labeled core proteins derived from either low or high affinity monomer preparations migrated as a single major species on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with electrophoretic mobility very similar to that of core protein derived from extracted proteoglycan monomer. Purified low affinity monomers were converted to the high affinity form by treatment at pH 8.6; however, this change was prevented by guanidinium-HCl at concentrations above 0.8 M.

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

    Alhabib, Salman F.; Saliba, Issam

    2017-01-01

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

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

    PubMed

    Lapcík, L; Chabrecek, P; Stasko, A

    1991-10-15

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

  20. Methodology for teaching facial filling with hyaluronic acid.

    PubMed

    De Oliveira Ruiz, R; Laruccia, M M; Gerenutti, M

    2014-01-01

    This paper shows the importance of the methodization in teaching facial dermal filling on the training of physicians who intend to work or are already working in the area of facial aesthetics. The methodology is based on the procedures performed in Iz Clinic of Plastic Surgery from 2007 to 2010, where the results of the use of dermal filling products were observed. We chose the hyaluronic acid for the methodization of education. Even being a safe procedure, the dermal filling needs to be done by trained professionals because some complications may occur. The theoretical discussion of facial anatomy, physiology and classification of aging, rheological characteristics of products and application techniques underpin the practical part, in which the live demo or supervision of the procedure is performed. The idealization of classes, both theoretical and practical, proposed in this work proved to be of great value in teaching physicians. The success of this method can be seen from the results achieved by students and by observing the drop in reports of adverse effects. After learning the techniques of facial dermal filling with products based on hyaluronic acid, a doctor may perform this therapy with other fillers, with harmonious results.

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

    PubMed

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

    2016-11-01

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

  2. Synthesis of hyaluronic acid by human peritoneal mesothelial cells: effect of cytokines and dialysate.

    PubMed

    Breborowicz, A; Korybalska, K; Grzybowski, A; Wieczorowska-Tobis, K; Martis, L; Oreopoulos, D G

    1996-01-01

    To assess effects of the inflammatory cytokines (IL-1-beta, TNF-alpha, TGF-beta 1) and dialysate effluent on synthesis of hyaluronic acid by human peritoneal mesothelial cells (HMC) in in vitro culture. Dialysate effluent was collected after the overnight dwell of Dianeal 1.5% from patients during CAPD training. HMC were obtained from omentum from nonuremic donors or were harvested from the dialysate effluent from CAPD patients. Synthesis of hyaluronic acid was studied on monolayers of HMC, which were deprived of serum 48 hours prior to experiment. Effects of cytokines were tested in a medium with low serum concentration (0.1%) or in medium mixed (1:1 v/v) with the autologous dialysate. Hyaluronic acid level in medium was measured with radioimmunoassay. Cytokines enhanced synthesis of hyaluronic acid by HMC, and the strongest effect was induced by IL-1. Effluent dialysate stimulates synthesis of hyaluronic acid stronger than 10% FCS. Effluent dialysate and IL-1 synergistically enhance synthesis of hyaluronic acid by HMC. Effluent dialysate from CAPD patients stimulates production of hyaluronic acid by HMC and acts synergistically with cytokines.

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

    PubMed

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

    2017-04-01

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

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

    PubMed

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

    2014-10-01

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

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

    PubMed

    Fernández, S; Córdoba, M

    2014-12-01

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

  6. Rheologic behavior of osteoarthritic synovial fluid after addition of hyaluronic acid: a pilot study.

    PubMed

    Mathieu, Pierre; Conrozier, Thierry; Vignon, Eric; Rozand, Yves; Rinaudo, Marguerite

    2009-11-01

    Viscosupplementation is a symptomatic treatment of osteoarthritis (OA) intended to restore rheologic homeostasis of the synovial fluid by injecting hyaluronic acid intraarticularly. Despite the long history of this therapy, little is known about its mechanisms of action and differences between commercial preparations. We investigated the rheologic behavior of OA synovial fluid with time, when stored at 4 degrees C, before and after the addition of two hyaluronic acid commercial preparations (linear and cross-linked). Thirteen OA synovial fluids were stored at 4 degrees C and assayed using steric exclusion chromatography, which allows hyaluronic acid to be separated from the remaining pool of proteins and its molecular weight and concentration to be determined without any pretreatment and calibration. The synovial fluid rheology also was studied in vitro, before and after addition of two viscosupplements, over 6 weeks. The non-Newtonian behavior of synovial fluid throughout followup appears to be the result of loose interactions between proteins and hyaluronic acid. When mixed with the linear hyaluronic acid, synovial fluid becomes less non-Newtonian whereas the non-Newtonian behavior was reinforced when mixed with the cross-linked hyaluronic acid. The rheology was nearly unchanged for all synovial fluids over 6 weeks. Our preliminary trial shows it is possible to study synovial fluid, stored at 4 degrees C, over a long time and suggests the enzymatic degradation of hyaluronic acid is negligible under these experimental conditions.

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

    PubMed Central

    2011-01-01

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

  8. Biomechanical and histological effects of intra-articular hyaluronic acid on anterior cruciate ligament in rats.

    PubMed

    Yucel, Istemi; Karaca, Erkut; Ozturan, Kutay; Yildirim, Umran; Duman, Seckin; Degirmenci, Erdem

    2009-08-01

    The histologic and biomechanical effects of intra-articular hyaluronic acid on the anterior cruciate ligaments of rats were investigated. Thirty rats were divided into three groups, i.e., the hyaluronic acid group, saline group, and control group. The hyaluronic acid and saline groups received a total of four intra-articular injections, whereas no injection was administered to the control group. The hyaluronic acid group was injected with 50 microg (0.05 cc) hyaluronic acid, and the saline group was injected with 50 microl (0.05 cc) of 0.9% sodium chloride solution. All of the rats were sacrificed on day 29 and the femur-anterior cruciate ligament-tibia complexes from the right knees were prepared, tested mechanically, and evaluated histologically. The mode of failure involved the midsubstance of the anterior cruciate ligament in all the specimens. There were no statistically significant differences in the stiffness and ultimate load to failure values between the three groups (P>0.05). The energy to failure values were evaluated and there was no statistically significant difference between the groups (P=0.064, chi-square=3.43). In the histologic analyses, there was a significant difference in the hyalinization values between the hyaluronic acid and saline groups (P=0.029) and between the hyaluronic acid group and control groups (P=0.029). The present study shows that intra-articularly delivered hyaluronic acid has no statistically significant effect on the tensile strength of the rat anterior cruciate ligament. Although hyalinization was increased, no difference was found on the other markers for degenerative changes. We conclude that intra-articular hyaluronic acid injections can be performed safely, although the use of a precise injection technique is recommended.

  9. Biophysical characteristics of hyaluronic acid soft-tissue fillers and their relevance to aesthetic applications.

    PubMed

    Sundaram, Hema; Cassuto, Daniel

    2013-10-01

    The purpose of this study was to present new rheologic data for hyaluronic acid filler products, correlate them with recent tissue integration studies, and provide a scientific rationale for selecting appropriate products for volume replacement within different tissue levels and anatomical zones. A brief overview of the methodology of filler rheology studies and data analysis is provided. Six U.S. Food and Drug Administration–approved, cross-linked, nonanimal-derived hyaluronic acid filler products and one hyaluronic acid product approved in Europe and elsewhere were studied: one cohesive polydensifiedmatrix hyaluronic acid (Belotero Balance, also known as Belotero Basic), two Hylacross hyaluronicacids (Juvéderm Ultra and Juvéderm Ultra Plus), one Vycross hyaluronic acid (Juvéderm Voluma), and three nonanimal stabilized hyaluronic acids (Perlane, Restylane and Restylane SubQ) [corrected].The elastic modulus, complex viscosity, and viscous modulus of each filler gel were quantified. Tan delta for each filler gel and also for calcium hydroxylapatite filler (Radiesse) was calculated at 0.7 Hz. Cohesive polydensified matrix hyaluronic acid (Belotero Balance) has the lowest elasticity and viscosity and the highest tan delta. This predicts its soft, flowing qualities and correlates with its homogeneous pattern of tissue integration after intradermal implantation. Nonanimal stabilized hyaluronic acid (Perlane and Restylane) has the highest elasticity and viscosity and low tan delta. This predicts its firm, less flowing qualities and correlates with a bolus-like pattern of tissue integration. Hylacross hyaluronic acid (Juvéderm) has intermediate elasticity, viscosity, and tan delta, correlating with its intermediate pattern of tissue integration. Rheologic evaluation reliably predicts tissue integration patterns and appropriate clinical applications of the studied fillers. Paradigms of layered filler placement can be designed to optimally address individual patient

  10. 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.

  11. 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.

  12. [Studies on hyaluronic acid as dendifier in Shuanghuanglian eye-drops].

    PubMed

    Ma, Man-ling; Liu, Lu; Sun, Shu-ying

    2005-08-01

    To study the possibility of hyaluronic acid as densifier of Shuanguangliao eye-drops. The factors related with hyaluronic acid s viscosity, such as pH-value and storing temperature, are tested in this experiment. At the same time, we checked the stimulation, stability of the densifier. There was not effect on viscosity of pH-value and storing temperature. No stimulation on the eye was found after densified with hyaluronic acid. The viscosity properties of hyaluronic acid are stablile. The hyaliuronic acid added to Shuanghuanglian eye-drops are stabiliable and it can be applied in eye-drops. The increased viscosity is benefit to extend the residence time of drug in eye.

  13. Skin Necrosis from Intra-articular Hyaluronic Acid Injection.

    PubMed

    Kim, Whan B; Alhusayen, Raed O

    2015-01-01

    Tissue necrosis is a rare yet potentially serious complication of intra-articular (IA) hyaluronic acid (HA) injections for treatment of knee osteoarthritis. To report a case of a patient with cutaneous necrosis after IA HA injection for treatment of knee osteoarthritis, presenting as a livedoid violaceous patch on the right knee. We report a case of cutaneous necrosis as a rare complication of IA HA injection for treatment of knee osteoarthritis. A literature review was undertaken of similar cases. Use of HA IA injections in the treatment of osteoarthritis can result in similar skin necrosis at uncommon anatomic locations corresponding to the site of HA injection. Although tissue necrosis is a rare complication, physicians need to be aware of this possibility as a complication of HA IA injections in the treatment of osteoarthritis and should be mindful of potential treatment options to manage this adverse event. © 2014 Canadian Dermatology Association.

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

    PubMed

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

    2013-12-01

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

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

    PubMed

    Ishii, Hidenori; Sakata, Kazuaki

    2014-01-01

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

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

    PubMed

    Giji, Sadhasivam; Arumugam, Muthuvel

    2014-01-01

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

  17. 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.

  18. 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.

  19. 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.

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

    PubMed Central

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

    2017-01-01

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

  1. Hyaluronic acid gel in the treatment of empty nose syndrome.

    PubMed

    Modrzyński, Marek

    2011-01-01

    Empty nose syndrome (ENS) along with atrophic rhinitis are disease entities that are bothersome for patients and difficult for their doctors to treat. The purpose of this study was to evaluate the usefulness of intranasal injection of hyaluronic acid (HA) gel in patients with symptoms of ENS. Three patients suffering from ENS and atrophic rhinitis underwent trial treatment consisting of submucosal injections of HA preparations into the inferior nasal concha and under the mucous membrane of the septum. As a result of treatment, the patients' symptoms improved for several months and no complications were recorded. Because of its simplicity, safety, and fairly good, but impermanent clinical effects, HA injections appear to be worth considering in less severe forms of ENS.

  2. Stretchable conductive polypyrrole films modified with dopaminated hyaluronic acid.

    PubMed

    Texidó, Robert; Orgaz, Antonio; Ramos-Pérez, Victor; Borrós, Salvador

    2017-07-01

    In this paper, we report the modification of polypirrole (PPy) with dopaminated hyaluronic acid (HADA). This design improves PPy adhesion onto stretchable materials such as poly(dimethylsiloxane) (PDMS) allowing the formation of conducting films on this kind of very flexible, hydrophobic materials. The results revealed that described PPy modification allows to obtain stable PPy:HADA nano-suspension able to cast films directly on PDMS. The comparison of PPy:HADA films with conventional PPy and other modified PPy shows that the modification improved the strength of the films under tension stress and their water resistance. Moreover, the modification proposed does not affect significantly the conductivity of the PPy films. The resulting properties of the material make it especially suitable for bio-integrated device applications, where a biocompatible material with stable electrical behaviour under deformation and water media is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Comprehensive Treatment of Periorbital Region with Hyaluronic Acid

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1995-01-01

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

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

    PubMed

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

    2009-12-01

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

  6. 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.

  7. 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

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

    PubMed

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

    2013-12-01

    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.

  9. A biocompatible calcium salt of hyaluronic acid grafted with polyacrylic acid.

    PubMed

    Nakagawa, Yoshiyuki; Nakasako, Satoshi; Ohta, Seiichi; Ito, Taichi

    2015-03-06

    We have synthesized hyaluronic acid (HA) grafted with polyacrylic acid (PAA) via controlled radical polymerization (CRP) in aqueous media. The grafted HA (HA-g-PAA) showed slow degradation by hyaluronidase compared with unmodified HA as a result of the steric hindrance produced by grafted PAA, and PAA was detached by hydrolysis and enzymatic degradation by lipase. It formed an insoluble salt immediately after mixing with Ca(2+) by the binding between grafted PAA and Ca(2+). Both HA-g-PAA and its salt showed good biocompatibility, especially to mesothelial cells in vitro. Finally, they were administered into mice subcutaneously and intraperitoneally. The residue of the material was observed 7 days after subcutaneous administration, while the material was almost cleared from the peritoneum 7 days after intraperitoneal administration with or without Ca(2+). HA-g-PAA is expected to be applicable to medical uses such as drug delivery in the peritoneum and for materials preventing peritoneal adhesion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Collagen and hyaluronic acid hydrogel in water-in-oil microemulsion delivery systems.

    PubMed

    Kupper, Sylwia; Kłosowska-Chomiczewska, Ilona; Szumała, Patrycja

    2017-11-01

    The increase in skin related health issues has promoted interest in research on the efficacy of microemulsion in dermal and transdermal delivery of active ingredients. Here, we assessed the water-in-oil microemulsion capacity to incorporate two natural polymers, i.e. collagen and hyaluronic acid with low and high molecular weight. Systems were extensively characterized in terms of conductivity, phase inversion studies, droplet diameter, polydispersity index and rheological properties. The results of this research indicate that the structure and extent of water phase in microemulsions is governed by ratio and amount of surfactant mixture (sorbitan ester derivatives). However, results have also shown that collagen, depending upon the weight of the molecule and its surface activity, influence the droplet size of the microemulsions. While the hyaluronic acid, especially with high molecular weight, due to the water-binding ability and hydrogel formation alters the rheological properties of the microemulsion, thus providing viscous consistency of the formulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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.

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

    PubMed Central

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

    2016-01-01

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

  13. 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

  14. The effects of hyaluronic acid vaginal gel on the vaginal epithelium of ovariectomized rats.

    PubMed

    Liu, Shuai-Bin; Liu, Shao-Li; Gan, Xiao-Ling; Zhou, Qin; Hu, Li-Na

    2015-03-01

    Hyaluronic acid is one of the best materials of water retention which can be used in vaginal atrophy. This study is to evaluate the role and mechanism of the hyaluronic acid vaginal gel (Hyalofemme) in the vaginal epithelium of ovariectomized rats. Sixty SD rats were randomly divided into control group (Sham ovariectomy, Sham-OVX), tendency group (ovariectomy, OVX), and experiment group (ovariectomy+Hyalofemme, OVX+Hyalofemme). The hyaluronic acid vaginal gel was administered local vaginal therapy to the experiment group with cytologicaly confirmed vaginal atrophy. The doses were adjusted by animal weight according to human dosage. After daily treatment for 14 days, VEGF and P-AKT activations were detected by Western blot in the experiment group. The hyaluronic acid vaginal gel proved to be very effective in the cytological reversal of vaginal atrophy but did not increase uterine weight. Vaginal microecosystem indicators were negative in the control group and the experiment group. By contrast, the indicators were positive in the tendency group. Hyaluronic acid vaginal gel is effective in the reversal of vaginal atrophy and is beneficial for improving vaginal microecosystem in the postmenopausal rat model. The hyaluronic acid vaginal gel can also improve the repair capacity of the vaginal epithelium.

  15. Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis.

    PubMed

    Siódmiak, Jacek; Bełdowski, Piotr; Augé, Wayne K; Ledziński, Damian; Śmigiel, Sandra; Gadomski, Adam

    2017-09-04

    Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing.

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

    PubMed

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

    2017-01-31

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

  17. 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.

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

    PubMed

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

    2017-01-01

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

  19. Randomized prospective evaluation of adjuvant hyaluronic acid therapy administered after knee arthroscopy.

    PubMed

    Westrich, Geoffrey; Schaefer, Sarah; Walcott-Sapp, Sarah; Lyman, Stephen

    2009-12-01

    Intra-articular injections of hyaluronic acid products may eliminate pain, improve mobility and quality of life, and delay osteoarthritis progression. In this study, we evaluated the safety and efficacy of sodium hyaluronate injections given after knee arthroscopy. Forty-six patients with early osteoarthritis and a symptomatic meniscus tear were prospectively randomized into study (injection) and control groups and underwent knee arthroscopy. Study patients received 3 sodium hyaluronate injections after surgery. Study and control outcomes were compared 3 and 6 months after surgery. The injection patients had significantly less pain (visual analog scale) at 3-month follow-up and more flexion at 6-month follow-up. Tenderness, pain on motion, and crepitus were significantly more likely to be absent from injection patients at the 3- and 6-month follow-ups. Patients with osteoarthritis and a symptomatic meniscus tear may experience more pain relief and functional mobility after arthroscopic surgery plus hyaluronic acid injections than after arthroscopy alone.

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

    PubMed

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

    2011-01-01

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

  1. Immunostimulatory and antiangiogenic activities of low molecular weight hyaluronic acid.

    PubMed

    Ke, Chunlin; Wang, Di; Sun, Yi; Qiao, Deliang; Ye, Hong; Zeng, Xiaoxiong

    2013-08-01

    The immunostimulatory activities of two low molecular weight hyaluronic acids (LMWHA-1 and LMWHA-2 with MW of 1.45×10(5) and 4.52×10(4) Da, respectively) and HA (MW, 1.05×10(6) Da) were evaluated by using in vitro cell models and in vivo animal models, and their effects on angiogenesis were measured in vivo by using the chick embryo chorioallantoic membrane (CAM) assay. The results demonstrated that LMWHA-1, LMWHA-2 and HA could promote the splenocyte proliferation, increase the activity of acid phosphatase in peritoneal macrophages and strengthen peritoneal macrophages to devour neutral red in vitro in a dose-dependent manner. Furthermore, LMWHA-1 and LMWHA-2 exhibited much stronger immunostimulatory activity than HA. For assay in vivo, LMWHA-1 and LMWHA-2 significantly increased the indices of spleen and thymus, the activity of lysozyme in serum and the swelling rate of earlap in delayed-type hypersensitivity in a dose-dependent manner. In the CAM model, the results showed that LMWHA-1, LMWHA-2 and HA suppressed angiogenesis in chicken embryos. Moreover, LMWHA-1 exhibited higher antiangiogenesis activity than LMWHA-2 and HA. All these results suggested that LMWHA might be a potential natural immunomodulator and a potential candidate compound for antiangiogenic. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Enzymatically Cross-linked Alginic-Hyaluronic acid Composite Hydrogels As Cell Delivery Vehicles

    PubMed Central

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

    2013-01-01

    An injectable composite gel was developed from alginic and hyaluronic acid. The ezymatically 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 tryaminated polymer solutions in 10U HRP and treating with 1.0% H2O2. The properties of the alginate gels were significanly 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

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

    PubMed Central

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

    1981-01-01

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

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

    PubMed Central

    2013-01-01

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

  5. 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

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

    PubMed Central

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

    2016-01-01

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

  7. 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.

  8. LSMO Nanoparticles Coated by Hyaluronic Acid for Magnetic Hyperthermia

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

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

    PubMed

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

    2016-03-10

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

  10. Carbon nanotubes induced gelation of unmodified hyaluronic acid.

    PubMed

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

    2013-08-13

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

  11. 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

  12. 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.

  13. 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

  14. Clinical experience with hyaluronic acid-filler complications.

    PubMed

    Park, Tae-Hwan; Seo, Sang-Won; Kim, June-Kyu; Chang, Choong-Hyun

    2011-07-01

    Hyaluronic acid (HA) fillers have become the material of choice for soft-tissue augmentation. HA fillers are longer lasting, less immunogenic and can be broken down by hyaluronidase. These advantages make HA fillers the most common of the temporary fillers on the market. However, early and delayed complications, ranging from minor to severe, can occur following HA-filler injection. We evaluated and treated 28 cases of HA-filler-related complications that were referred to our hospital over a period of 5 years from July 2004 to October 2009. Twenty-eight patients were included in our study; 82.1% of the patients were female and 17.9% were male. Complications were roughly classified as nodular masses, inflammation, tissue necrosis and dyspigmentation. Affected locations, in descending order of frequency, were the perioral area, forehead, including glabella, nose, nasolabial fold, mentum, including marionette wrinkles, cheek area and periocular wrinkles. The most disastrous complication was alar rim necrosis following injection of the nasolabial fold. We propose two 'danger zones' that are particularly vulnerable to tissue necrosis following filler injection: the glabella and nasal ala. Although there is no definite treatment modality for the correction of HA-filler complications, we have managed them with various available treatment modalities aimed at minimising patient morbidity. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-09-22

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

  16. Factors Affecting the Rheological Measurement of Hyaluronic Acid Gel Fillers.

    PubMed

    Lorenc, Z Paul; Öhrlund, Åke; Edsman, Katarina

    2017-09-01

    With the number of available dermal fillers increasing, so is the demand for scientifically based comparisons, often with rheological properties in focus. Since analytical results are always influenced by instrument settings, consensus on settings is essential to make comparison of results from different investigators more useful. Preferred measurement settings for rheological analysis of hyaluronic acid (HA) fillers are suggested, and the reasoning behind the choices is presented by demonstrating the effect of different measurement settings on select commercial HA fillers. Rheological properties of 8 HA fillers were measured in a frequency sweep from 10 to 0.01 Hz at 0.1% strain, using an Anton Paar MCR 301, a PP-25 measuring system with a gap of 1 mm at 25°C. A 30-min period was used for relaxation of the sample between loading and measuring. The data presented here, together with previously published data, demonstrate differences in G' from 1.6 to 7.4 times for the same product. A large part of the differences were concluded to be due to differences in rheometry measurement settings. The confusion from the many parameters involved in rheometry can be avoided by simply using the elastic modulus (G') to differentiate products.

    J Drugs Dermatol. 2017;16(9):876-882.

    .

  17. Hyaluronic acid in ankle osteoarthritis: why evidence of efficacy is still lacking?

    PubMed

    Abate, Michele; Schiavone, Cosima; Salini, Vincenzo

    2012-01-01

    Intra-articular injections of hyaluronic acid (HA) are useful in the treatment of osteoarthritis (OA), as shown by studies on knee, hip, and trapezio-metacarpal joints. The positive results can be explained by several factors: the restoration of elastic and viscous properties of intra-articular fluid, the anti-inflammatory and the anti-nociceptive activity, and the normalisation of hyaluronan synthesis and inhibition of hyaluronic acid degradation. However, evidence of efficacy of hyaluronic acid in ankle osteoarthritis is still lacking: several studies have been performed without a control group, or have shown similar results to those obtained with different therapeutic procedures. The aim of this paper is to analyse the reasons which can explain the discrepancy between the sound biological background and the inconclusive clinical results. First, it must be considered that the ankle joint, from a biomechanical point of view, is more complex than other joints, and that greater stress is sustained by the articular surfaces. Second, the limited benefit can be related to the use of hyaluronic acid mostly in cases of post-traumatic osteoarthritis, where the treatment must be addressed to solve the biomechanical problems, and then to restore the rheological properties of the ankle joint. A third important explanation of the failure may be the improper technique of administration, that has been performed in all studies, but one, without imaging guidance. Indeed, it is well known that hyaluronic acid, if not delivered directly into the intra-articular space, is unlikely to be effective.

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

    PubMed

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

    1989-04-01

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

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

    PubMed

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

    2011-11-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2002-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. 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.

  4. Therapeutic effect of Intra-Tympanic Dexamethasone-Hyaluronic Acid Combination in Sudden Sensorineural Hearing Loss.

    PubMed

    Rogha, Mehrdad; Kalkoo, Amin

    2017-09-01

    Hearing loss is fairly a common disorder which is usually treated with corticosteroids via systemic administration and/or intra-tympanic injection. This study aimed to compare the effectiveness of intra-tympanic injections of dexamethasone with its combination with hyaluronic acid in patients with sudden sensorineural hearing loss. In this clinical trial, 40 patients were randomly assigned to two groups; in the first group, 20 patients received 2.4 mg intra-tympanic dexamethasone, while in the second group patients received injections of 2.4 mg of dexamethasone plus 2 mg of hyaluronic acid in combination. Patients in both groups were injected every other day to a total of three injections. The hearing status of patients was evaluated by pure tone audiometry (bone conduction threshold) before and 2 weeks after the intervention. Assessment of hearing threshold before and after treatment in the two groups showed a significant difference between hearing thresholds at frequencies of 4,000 to 8,000 Hz (P<0.001). The difference at other frequencies was not meaningful; however, in general, we found a better therapeutic effect in patients who received the combination of dexamethasone and hyaluronic acid. A combination of dexamethasone and hyaluronic acid in patients with sudden sensorineural hearing loss may be more effective than dexamethasone alone. Because hyaluronic acid lacks certain side effects, and also makes it possible to reduce the steroid dose, we recommend the use of this combination in the treatment of patients with sudden sensorineural hearing loss.

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

    PubMed

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

    1987-03-01

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

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

    PubMed

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

    2017-03-16

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

  7. 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

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

    PubMed

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

    2008-10-01

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

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

    PubMed

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

    2011-05-01

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

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

    PubMed

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

    2013-11-01

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

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

    PubMed

    Suri, Shalu; Schmidt, Christine E

    2009-09-01

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

  12. Quantitative Correlation Between Hyaluronic Acid Filler and Hyaluronidase.

    PubMed

    Hwang, Euna; Song, You Seong

    2017-05-01

    The hyaluronic acid-based filler (HA filler) is used worldwide in various applications. In particular, the HA filler is used in the plastics and cosmetic medical field for facial rejuvenation and contouring. In this setting, it is injected into the skin or underlying tissue. Complications of HA filler injection have been relieved using hyaluronidase. However, there is no standard dose to adjust for undesirable HA filler lumpness. In this study, the authors tried to analyze any quantitative correlation between HA filler and hyaluronidase. The back of each rat (total 14 rats) was divided into 4 sites. A volume of 0.5 mL HA filler was injected into the subdermal layer at each site and HA filler nodules were created on the dorsum of each rat. Each nodule was allocated to groups 1, 2, 3, and 4 according to the different concentrations of hyaluronidase. As a result, the injected HA filler volume doubled within 4 days of injection, and then decreased slowly thereafter in group 1 (control group with normal saline only). A 30 unit hyaluronidase treatment compensated for the initial volume increase (approximately 30%) with HA filler (0.5 ml) at the fourth day. Sixty units of hyaluronidase reduced the initial volume (0.5 mL) of overinjected or misplaced HA filler on the fourth day. Approximately 90 units of hyaluronidase can reduce to the volume by 0.25 mL (50%) of the injected HA filler on the fourth day. The authors believe that this quantitative analysis of hyaluronidase concentration is helpful to plan the amount of hyaluronidase for correction of HA filler injection errors.

  13. Hyaluronic Acid-Human Blood Hydrogels for Stem Cell Transplantation

    PubMed Central

    Chang, Connie Y.; Chan, Angel; Armstrong, Patrick; Luo, Hong-Chang; Higuchi, Takahiro; Strehin, Iossif; Vakrou, Styliani; Lin, Xiaoping; Brown, Sophia; O’Rourke, Brian; Abraham, Theodore P.; Wahl, Richard; Steenbergen, Charles; Elisseeff, Jennifer; Abraham, M. Roselle

    2012-01-01

    Tissue engineering-based approaches have the potential to improve stem cell engraftment by increasing cell delivery to the myocardium. Our objective was to develop and characterize a naturally-derived, autologous, biodegradable hydrogel in order to improve acute stem cell retention in the myocardium. HA-blood hydrogels(HA-Bl) were synthesized by mixing in a 1:1(v/v) ratio, lysed whole blood and hyaluronic acid(HA), whose carboxyl groups were functionalized with N-hydroxysuccinimide(NHS) to yield HA succinimidyl succinate(HA-NHS). We performed physical characterization and measured survival/proliferation of cardiosphere-derived cells(CDCs) encapsulated in the hydrogels. Hydrogels were injected intramyocardially or applied epicardially in rats. NHS-activated carboxyl groups in HA react with primary amines present in blood and myocardium to form amide bonds, resulting in a 3D hydrogel bound to tissue. HA-Bl hydrogels had a gelation time of 58±12s, swelling ratio of 10±0.5, compressive and elastic modulus of 14±3 and 1.75±0.6 kPa respectively. These hydrogels were not degraded at 4wks by hydrolysis alone. CDC encapsulation promoted their survival and proliferation. Intra-myocardial injection of CDCs encapsulated in these hydrogels greatly increased acute myocardial retention(p=0.001). Epicardial application of HA-blood hydrogels improved left ventricular ejection fraction following myocardial infarction (P=0.01). HA-blood hydrogels are highly adhesive, biodegradable, promote CDC survival and increase cardiac function following epicardial application after myocardial infarction. PMID:22898181

  14. Hyaluronic acid levels are increased in complicated parapneumonic pleural effusions.

    PubMed

    Zaga, T; Makris, D; Tsilioni, I; Kiropoulos, T; Oikonomidi, S; Damianos, A; Gourgoulianis, K I

    2011-09-01

    Hyaluronic acid (HA) is a component of extracellular matrix and may play a role in the pleural inflammation which is implicated in parapneumonic effusions.The aim of the current study was to investigate HA levels in serum and pleura in patients with parapneumonic effusions. We prospectively studied pleural and serum levels of HA in 58 patients with pleural effusions due to infection (complicated and uncomplicated parapneumonic effusions), malignant effusions and transudative effusions due to congestive heart failure. In addition to HA, TNF-alpha and IL-beta levels were determined in pleural fluid and serum by ELISA. The median +/- SD HA levels (pg/ml) in pleural fluid of patients with complicated effusions (39.058 +/- 11.208) were significantly increased (p < 0.005), compared to those with uncomplicated parapneumonic effusions (11.230 +/- 1.969), malignant effusions (10.837 +/- 4.803) or congestive heart failure (5.392 +/- 3.133). There was no correlation between pleural fluid and serum HA values. Pleural fluid TNF-alpha levels (146 +/- 127 pg/mL) and IL-1beta levels (133.4 +/- 156 pg/mL) were significantly higher in patients with complicated parapneumonic effusions compared to patients with other types of effusion (p < 0.05). No significant association between HA and TNF-alpha or IL-1beta was found. CONCLUSIONS. HA may play a significant role in the inflammatory process which characterises exudative infectious pleuritis. Further investigation might reveal whether HA is a useful marker in the management of parapneumonic effusions.

  15. Hyaluronic acid on collagen membranes: An experimental study in rats.

    PubMed

    Silva, Edson Costa E; Omonte, Sheyla Viana; Martins, Alessandro Gomides Veiga; de Castro, Hércules Henrique Onibene; Gomes, Hayder Egg; Zenóbio, Élton Gonçalves; de Oliveira, Peterson Antônio Dutra; Horta, Martinho Campolina Rebello; Souza, Paulo Eduardo Alencar

    2017-01-01

    The aim of this study was to evaluate the effect of hyaluronic acid (HA) in the structure and degradation patterns of BioGide(®) and OsseoGuard™ collagen membranes. HA mediates inflammation and acts in cell migration, adhesion, and differentiation, benefitting tissue remodeling and vascularization. These are desirable effects in guided regeneration procedures, but it is still unknown whether HA alters the barrier properties of absorbable membranes. Bone defects were created in the calvaria of rats, which were treated with HA gel 1% (HA group) or simply filled with blood clot (control group), and covered with BioGide(®) or OsseoGuard™. The animals were euthanized after 1, 30, and 60days, and their calvarias were processed for histological analysis. BioGide(®), in both HA and control groups, showed vascularization, intense cell colonization, bone formation, and tissue integration at 30 and 60days. In contrast, Osseoguard™ presented minimal cellular colonization, and inflammatory reaction associated to foreign body reaction in both time points and groups. The HA group of BioGide(®) showed higher cell colonization (574.9±137.6) than the control group (269.1±70.83) at 60days (p<0.05). Despite this finding, the structure and degradation pattern were similar for BioGide(®) and Osseoguard™ in the HA and control groups. The results suggest that HA did not interfere with tissue integration and structural degradation of BioGide(®) and Osseoguard™ membranes. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  17. 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.

  18. 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

  19. Hyaluronic acid enhances gene delivery into the cochlea.

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2013-12-28

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

  1. [Intra-articular injections of hyaluronic acid for anterior disc displacement of temporomandibular joint].

    PubMed

    Long, X

    2017-03-09

    Anterior disc displacement (ADD) of temporomandibular joint (TMJ) is regarded as one of the major findings in temporomandibular disorders (TMD). It is related to joint noise, pain, mandibular dysfunction, degenerative change and osteoarthritis. In the mean time, the pathological changes were found in synovial membrane and synovial fluid. Hyaluronic acid is a principal component of the synovial fluid which plays an important role in nutrition, lubrication, anti-inflammation and cartilage repair. The synthesis, molecule weight, and concentration of hyaluronic acid are decreased during TMD and cause TMJ degenerative changes. The clinical conditions, pathological changes, the mechanism of action for hyaluronic acid and the treatment of anterior disc displacement of TMJ are discussed in this article.

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

    PubMed

    Zhang, Zhenhuan; Christopher, Gordon F

    2015-04-07

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

  3. 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

  4. 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.

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

    PubMed

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

    2015-07-13

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

  6. 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

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

    PubMed

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

    2010-06-01

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

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

    PubMed

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

    2017-02-16

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

  9. 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

  10. Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials.

    PubMed

    Wang, Chen-Ti; Lin, Jinn; Chang, Chee-Jen; Lin, Yu-Tsan; Hou, Sheng-Mou

    2004-03-01

    The magnitude of the therapeutic effects of intra-articular injection of hyaluronic acid on osteoarthritis of the knee is still in question. The aim of this meta-analysis was to elucidate the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for osteoarthritis of the knee. We conducted a meta-analysis of twenty blinded randomized controlled trials that compared the therapeutic effect of intra-articular injection of hyaluronic acid with that of intra-articular injection of a placebo to treat osteoarthritis of the knee. The outcome end points were classified into three categories: pain with activities, pain without activities, and function. The outcome measures of the efficacy of hyaluronic acid were the mean differences in the efficacy scores between the hyaluronic acid and placebo groups. The outcome measure of the safety of hyaluronic acid was the relative risk of adverse events. Intra-articular injection of hyaluronic acid can decrease symptoms of osteoarthritis of the knee. We found significant improvements in pain and functional outcomes with few adverse events. However, there was significant between-study heterogeneity in the estimates of the efficacy of hyaluronic acid. Subgroup analysis and meta-regression analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher estimates of hyaluronic acid efficacy, that introduction of acetaminophen as an escape analgesic in the trial resulted in lower estimates of hyaluronic acid efficacy, and that patients older than sixty-five years of age and those with the most advanced radiographic stage of osteoarthritis (complete loss of the joint space) were less likely to benefit from intra-articular injection of hyaluronic acid. This meta-analysis confirmed the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for the treatment of osteoarthritis of the knee. Additional well-designed randomized controlled trials

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

    PubMed

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

    2017-03-17

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2008-05-01

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

  14. 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

  15. Cross-linked hyaluronic acid in pressure ulcer prevention.

    PubMed

    Beniamino, P; Vadalà, M; Laurino, C

    2016-07-02

    Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus

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

    PubMed

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

    2008-03-01

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

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

    PubMed

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

    2011-04-01

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

  18. Prognostic Factors after Intra-Articular Hyaluronic Acid Injection in Ankle Osteoarthritis

    PubMed Central

    Han, Seung Hwan; Kim, Tae Hun

    2014-01-01

    Purpose The goal of this study was to identify baseline prognostic factors of outcome in ankle osteoarthritis patients after intra-articular hyaluronic acid injection. Materials and Methods Patients with ankle osteoarthritis who received hyaluronic acid injection therapy were retrospectively reviewed. Each patient received weekly intra-articular hyaluronic acid injections (2 mL) for 3 weeks. Six predictors including gender, age, symptom duration, radiographic osteoarthritis stage, radiographic subchondral cyst, and fracture history were evaluated. Visual analogue scale (VAS) and patient satisfaction were evaluated as outcome measures. These predictors and outcome measurements were included in a logistic regression model for statistical analysis. Results Total of 40 consecutive patients (21 male, 19 female) were included in this study. Mean age was 60.6. Average follow up period was 13 months. The mean VAS recorded 3, 6, and 12 months after the first injection was 3.6 (SD 2.54, p<0.001), 4.33 (SD 2.9, p<0.001), and 5.3 (SD 2.7, p=0.0071), respectively, when compared to baseline VAS. Early stage disease was identified as an independent predictor associated with 'positive VAS outcome' at 3 and 6 months. Early stage disease and duration of pain less than 1 year were independent predictors associated with higher satisfaction. Conclusion While hyaluronic acid injection for ankle osteoarthritis is a safe and effective treatment, careful selection of patients should be made according to the above prognostic predictors. PMID:24954340

  19. Prognostic factors after intra-articular hyaluronic acid injection in ankle osteoarthritis.

    PubMed

    Han, Seung Hwan; Park, Do Young; Kim, Tae Hun

    2014-07-01

    The goal of this study was to identify baseline prognostic factors of outcome in ankle osteoarthritis patients after intra-articular hyaluronic acid injection. Patients with ankle osteoarthritis who received hyaluronic acid injection therapy were retrospectively reviewed. Each patient received weekly intra-articular hyaluronic acid injections (2 mL) for 3 weeks. Six predictors including gender, age, symptom duration, radiographic osteoarthritis stage, radiographic subchondral cyst, and fracture history were evaluated. Visual analogue scale (VAS) and patient satisfaction were evaluated as outcome measures. These predictors and outcome measurements were included in a logistic regression model for statistical analysis. Total of 40 consecutive patients (21 male, 19 female) were included in this study. Mean age was 60.6. Average follow up period was 13 months. The mean VAS recorded 3, 6, and 12 months after the first injection was 3.6 (SD 2.54, p<0.001), 4.33 (SD 2.9, p<0.001), and 5.3 (SD 2.7, p=0.0071), respectively, when compared to baseline VAS. Early stage disease was identified as an independent predictor associated with 'positive VAS outcome' at 3 and 6 months. Early stage disease and duration of pain less than 1 year were independent predictors associated with higher satisfaction. While hyaluronic acid injection for ankle osteoarthritis is a safe and effective treatment, careful selection of patients should be made according to the above prognostic predictors.

  20. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Oelschlaeger, C; Bossler, F; Willenbacher, N

    2016-02-08

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

  5. Use of hyaluronic acid gel in the treatment of lagophthalmos in sunken superior sulcus syndrome.

    PubMed

    Leyngold, Ilya M; Berbos, Zachary J; McCann, John D; Pariseau, Brett; Leyngold, Ariel R; Anderson, Richard L

    2014-01-01

    To evaluate the use of hyaluronic acid gel in the management of lagophthalmos in sunken superior sulcus syndrome. Lagophthalmos associated with orbital fat atrophy and deep superior sulcus is a known entity described previously. Orbital fat atrophy results in deep superior sulcus where skin, orbicularis muscle, and orbital septum retract posteriorly in the deep superior sulcus, leading to lagophthalmos from suboptimal orbicularis function and effective skin shortening. The authors define this condition as sunken superior sulcus syndrome (SSSS) when the deep superior sulcus leads to exposure keratopathy. Thus, the syndrome consists of deep superior sulcus, lagophthalmos, and exposure keratopathy. Although the use of hyaluronic acid gel has been proposed as a management option for paralytic lagophthalmos, its application in the treatment of lagophthalmos in SSSS has not been reported. In this study, 5 patients (10 eyelids) with SSSS were injected with hyaluronic acid gel in the superior sulcus of the upper eyelid. Injected amount was titrated until the desired point was reached: complete or nearly complete eyelid closure. After an average follow up of 9.5 months, lagoph thalmos improved by 2 mm or 69% (p = 0.02) on the right side and by 1 mm or 71% (p = 0.01) on the left side. Most patients also reported significantly improved ocular comfort and appearance of the superior sulcus. The only complications noted were bruising and temporary uneven contour of the upper eyelid sulcus. Management of lagophthalmos in SSSS with hyaluronic acid gel is an effective and safe alternative to surgery.

  6. 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.

  7. 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.

  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.

  9. 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.

  10. 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

  11. 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

  12. Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a ligand for attachment of group A Streptococcus to CD44 on human keratinocytes.

    PubMed Central

    Schrager, H M; Albertí, S; Cywes, C; Dougherty, G J; Wessels, M R

    1998-01-01

    We used wild-type and isogenic mutant strains of group A Streptococcus (GAS) that expressed M protein, capsule, or both to study the function of M protein and the hyaluronic acid capsular polysaccharide in attachment of GAS to human keratinocytes. Types 6 and 24, but not type 18, M protein were found to mediate attachment of GAS to soft palate or skin keratinocytes, but this interaction was prevented by the hyaluronic acid capsule on highly encapsulated, or mucoid, strains. Monoclonal antibody to CD44, the principal hyaluronic acid-binding receptor on keratinocytes, inhibited attachment of both highly encapsulated and poorly encapsulated wild type strains of GAS, but not the attachment of acapsular mutants. Transfection of K562 cells with cDNA encoding human CD44 conferred the capacity to bind each of six wild-type strains of GAS, but not to bind acapsular mutants. Because, in contrast to other potential adhesins, the group A streptococcal capsule is both highly conserved and surface-exposed, it may serve as a universal adhesin for attachment of diverse strains of GAS to keratinocytes of the pharyngeal mucosa and the skin. PMID:9541502

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

    PubMed Central

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

    2007-01-01

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

  14. Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

    SciTech Connect

    Svensson Holm, Ann-Charlotte B.; Bengtsson, Torbjoern; Grenegard, Magnus; Lindstroem, Eva G.

    2012-03-10

    Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodelling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in platelet-induced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation. The interaction between ASMC and platelets was studied by fluorescent staining of F-actin. In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling.

  15. Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis.

    PubMed

    McCarty, M F; Russell, A L; Seed, M P

    2000-05-01

    High-molecular-weight hyaluronic acid (HA) produced by the synovium may function physiologically to aid preservation of cartilage structure and prevent arthritic pain; both the size and concentration of HA in synovial fluid are diminished in osteoarthritis (OA). Glucosamine therapy for OA can be expected to increase synovial HA production by providing rate-limiting substrate. In addition, certain sulfated glycosaminoglycans and polysaccharides - including chondroitin sulfate (CS), dermatan sulfate, and pentosan polysulfate - stimulate synovial HA production, apparently owing to a hormone-like effect triggered by the binding of these polymers to membrane proteins of synovial cells. Surprisingly, a significant proportion of orally administered CS is absorbed as intact polymers - apparently by pinocytosis. These considerations may rationalize clinical studies concluding that oral CS provides slow-onset but durable pain relief and functional improvement in OA. The possibility that oral glucosamine and CS may interact in a complementary or synergistic fashion to improve synovial fluid HA content in OA should be assessed in clinical studies, and the potential of adjunctive CS administration to improve the clinical response achievable with optimal intakes of glucosamine should likewise be evaluated. In light of the fact that the synovium virtually functions as a 'placenta' for cartilage, focusing on synovium as the target for therapeutic intervention in OA may be a rational strategy.

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

    PubMed Central

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

    2016-01-01

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

  17. Exogenous and endogenous hyaluronic acid reduces HIV infection of CD4(+) T cells.

    PubMed

    Li, Peilin; Fujimoto, Katsuya; Bourguingnon, Lilly; Yukl, Steven; Deeks, Steven; Wong, Joseph K

    2014-10-01

    Preventing mucosal transmission of HIV is critical to halting the HIV epidemic. Novel approaches to preventing mucosal transmission are needed. Hyaluronic acid (HA) is a major extracellular component of mucosa and the primary ligand for the cell surface receptor CD44. CD44 enhances HIV infection of CD4(+) T cells, but the role of HA in this process is not clear. To study this, virions were generated with CD44 (HIVCD44) or without CD44 (HIVmock). Exogenous HA reduced HIV infection of unstimulated CD4(+) T cells in a CD44-dependent manner. Conversely, hyaluronidase-mediated reduction of endogenous HA on the cell surface enhanced HIV binding to and infection of unstimulated CD4(+) T cells. Exogenous HA treatment reduced activation of protein kinase C alpha via CD44 on CD4(+) T cells during infection with HIVCD44. These results reveal new roles for HA during the interaction of HIV with CD4(+) T cells that may be relevant to mucosal HIV transmission and could be exploitable as a future strategy to prevent HIV infection.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2016-11-01

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

  4. Is the addition of a polyol to hyaluronic acid a significant advance in the treatment of osteoarthritis?

    PubMed

    Conrozier, Thierry

    2017-07-10

    Viscosupplementation with intra-articular injections of hyaluronic acid is recommended as a second line treatment for knee OA, after failure of non-pharmacological modalities and usual pain killers. Nevertheless there is still controversies regarding clinical relevance of its effects. Research is looking at the best means to improve the performance of viscosupplementation in order to obtain a faster, more sustainable and more marked effect. Antioxidants have been assessed in combination with hyaluronic acid because the injected hyaluronate is rapidly degraded by the reactive oxygen species present in large amounts in the OA synovial fluid, limiting its residence time into the joint. Sorbitol and mannitol which have intrinsic free radical scavenger properties have been the most studied antioxidants. Sodium hyaluronate and polyols develop together a complex based on a dense network of hydrogen bonds that do not modify the visco-elsatic properties of hyaluronic acid. The oxygen free radicals neutralization by mannitol has been proven to delay the degradation of both linear and cross-linked HA in several in vitro models of oxidative stress. The antioxidant effect of these polyols may also play a role in accelerate onset of analgesia, as demonstrated in a double blind controlled trial comparing a mannitol-modified viscosupplement to regular hyaluronic acid. The addition of mannitol and sorbitol to hyaluronic acid does not alter the safety and local tolerability. In summary, adding a polyol to hyaluronic acid may improve the effects of viscosupplementation, by reducing the rate of degradation of HA that leads to an earlier effect on pain relief without increasing the risk of adverse effect. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. 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.

  6. Digital and interdigital corns: a report of two cases with use of hyaluronic acid gel filler.

    PubMed

    Brousseau-Foley, Magali; Cantin, Vincent

    2014-07-01

    Digital and interdigital corns are common painful foot conditions encountered by podiatrists during the course of their practice. These corns can often be treated with conservative techniques, although they tend to eventually recur. Currently, no single treatment exists that is efficient, long-lasting, minimally invasive, and easy to administer. This article describes two cases where hyaluronic acid gel injections were used to improve symptoms associated with digital and interdigital corns located in a nonweightbearing area. Both patients tolerated the intervention well and showed considerable improvement of their condition for a substantial period of time after the intervention without developing adverse reactions. Hyaluronic acid gel injections could very well represent an interesting therapeutic alternative for digital and interdigital corns located in nonweightbearing areas.

  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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2013-06-01

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

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

    PubMed

    Patel, Tapan; Tevet, Oren

    2015-01-01

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

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

    PubMed

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

    2010-10-11

    The short-term recovery period post-arthroscopic meniscectomy is characterized by pain and impaired function most likely related to the irrigation of synovial fluid from the knee intraoperatively. Consequently, along with removal of harmful debris, the irrigation fluid dilutes the hyaluronic acid layer covering the joint tissues. Hyaluronic acid contributes to the homeostasis of the joint environment and is an important component of synovial fluid and cartilage matrix. Hence, the instillation of hyaluronic acid after the procedure may relieve symptoms. This prospective, single-blind, randomized, controlled study evaluated clinical outcome after hyaluronic acid injection to patients who underwent arthroscopic meniscectomy of the knee. Patients with ligamentous injuries or severe chondral damage were excluded. Fifty-six patients with a mean age of 34 years (range, 17-44 years) were injected with Viscoseal (TRB Chemedica International S.A., Geneva, Switzerland) or normal saline immediately post-arthroscopy and divided into the Viscoseal group or control group, respectively. Patients were evaluated for pain, swelling, and function at 1, 4, and 12 weeks postoperatively. Patients in the control group reported more pain at week 1, with a mean visual analog score (VAS) of 43, than did patients in the Viscoseal group, with a mean VAS of 28 (P=.006). At 4 weeks postoperatively, none of the Viscoseal patients had consumed analgesics, where 9 (of 28) in the control group reported acetaminophen intake (P=.039). No significant difference in knee function was found between groups. Intra-articular injection of Viscoseal after arthroscopic meniscectomy reduced pain in the short-term recovery period. Copyright 2010, SLACK Incorporated.

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

    PubMed

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

    2015-01-01

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

  13. 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

  14. [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.

  15. Hyaluronic acid gel weight: a nonsurgical option for the management of paralytic lagophthalmos.

    PubMed

    Martín-Oviedo, Carlos; García, Irene; Lowy, Alex; Scola, Esteban; Aristegui, Miguel; Scola, Bartolome

    2013-12-01

    Management of lagophthalmos should be a priority in the treatment of patients with facial palsy. The aim of the study was to evaluate the safety and efficacy of injecting hyaluronic acid gel into the upper eyelid as a nonsurgical alternative for patients with temporary facial palsy. Retrospective study of 26 patients treated with hyaluronic acid gel injected into the pretarsal region of the upper eyelid. Measurements taken before and after treatment were standardized and compared using digitized photographs. Patients were followed up for 1 year, and overall outcomes were assessed. All patients initially demonstrated improvement in lagophthalmos, which decreased to 0.0 mm. After 1 month, a significant increase in lagophthalmos was observed in two patients (initial fissure of 8 and 9 mm), and a platinum weight was implanted to control keratopathy. The remaining patients (initial lagophthalmos below 6.5 mm) maintained the improvement until facial restoration. Only three patients had recurrent lagophthalmos (2 mm) due to resorption, which was resolved by injecting an additional 0.3 cc. The mean improvement in lagophthalmos was 4.6 mm (range, 3.5-6.5 mm). Complications included transient ecchymosis and minimal blepharoptosis due to nonreabsorption in five patients. These patients were successfully treated with hyaluronidase. Hyaluronic acid gel has proven effective in reducing paralytic lagophthalmos and controlling keratopathy in patients with temporary facial palsy, especially those with palpebral fissure with attempted closure no greater than 6.5 mm. Injection of hyaluronic acid gel is safe, quick, and easily performed. In addition, it is more cost-effective than surgery. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

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

    PubMed

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

    2015-05-01

    Polyelectrolyte multilayer films have been suggested as tunable substrates with flexible surface properties that can modulate cell behavior. However, these films' biological effects on neural stem/progenitor cells have rarely been studied. Herein, biomimetic multilayer films composed of hyaluronic acid and poly-L-lysine were chosen to mimic the native extracellular matrix niche of brain tissue and were evaluated for their inductive effects, without the addition of chemical factors. Because neural stem/progenitor cells are sensitive to substrate properties, it is important that this system provides control over the surface charge, and slight stiffness variations are also possible. Both of these factors affect neural stem/progenitor cell differentiation. The results showed that neural stem/progenitor cells were induced to differentiate on the poly-L-lysine/hyaluronic acid multilayer films with 0.5-4 alternating layers. In addition, the neurite outgrowth length was regulated by the surface charge of the terminal layer but did not increase with the layer number. In contrast, the quantity of differentiated neurons was enhanced slightly as the number of layers increased but was not affected by the surface charge of the terminal layer. In sum, material pairs in the form of native poly-L-lysine/hyaluronic acid films achieved important targets for neural regenerative medicine, including enhancement of the neurite outgrowth length, regulation of neuron differentiation, and the formation of a network. These extracellular matrix-mimetic poly-L-lysine/hyaluronic acid multilayer films may provide a versatile platform that could be useful for surface modification for applications in neural engineering. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. 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.

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

    PubMed

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

    2010-11-02

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

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

    PubMed Central

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

    2010-01-01

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

  20. Hyaluronic acid effect on adipose-derived stem cells. Biological in vitro evaluation.

    PubMed

    Moreno, A; Martínez, A; Olmedillas, S; Bello, S; de Miguel, F

    2015-01-01

    To evaluate the in vitro effects of hyaluronic acid (HA) on adipose-derived stem cells (ASC) in order to consider the possibility of their combined used in the treatment of knee arthrosis. The ASC cells were grown both in the presence and absence of AH, and several studies were carried out: proliferation (WST8) and cell viability studies (Alamar Blue® and Trypan Blue), possible chondrogenic differentiation (collagen type 2 expression) by RT-PCR, AH receptor expression (CD44) by flow cytometry and RT-QPCR, and expression of inflammatory and anti-inflammatory factors (IL-6, TGFß, IL-10) by RT-QPCR. The number of ASC significantly increased after 7 days with HA (158±39%, p <0.05). Additionally, the cell viability of the ASC treated with HA after 1, 3, 5 and 7 days was similar to that of the control cells, being considered non-toxic. There were no changes observed in the expression of CD44 and chondrogenic differentiation. TGFß expression was not modified after AH treatment, but there was a 4-fold decrease in IL-6 expression and IL-10 expression increased up to 2-fold compared to control cells. Hyaluronic acid favours ASC proliferation without causing cellular toxicity, and inducing an anti-inflammatory profile in these cells. Hyaluronic acid appears to be a suitable vehicle for the intra-articular administration of mesenchymal stem cells. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

  1. Preparation and properties of collagen/modified hyaluronic acid hydrogel for biomedical application.

    PubMed

    Kim, Jae-Kyung; Lee, Jung-Soo; Jung, Hyo-Jung; Cho, Jin-Hui; Heo, Jee-In; Chang, Yoon-Ho

    2007-11-01

    Hydrogels composed of collagen and hyaluronic acid are types of crosslinked water-swellable polymers and possess vast potential for applications in the medical industry. Collagen (Co) is the major structural protein of connective tissues such as skin, tendon and cartilage. Hyaluronic acid (HA) is a non-immunogenic, non-adhesive glycosaminoglycan that has a high water absorption property and plays significant roles in several cellular processes. The purpose of this study is to prepare a collagen (Co)-modified hyaluronic acid (MHA) hydrogel and investigate its potential utility for biomedical products such as wound dressing materials. Collagen (Co, type I) was obtained from pig skin and mucopolysaccharide-HA was modified by a poly (ethylene glycol) diglycidyl ether (PEGDGE) crosslinker. Thermal stability, swelling behavior, and mechanical strength of Co-MHA hydrogel according to different mass ratios of Co and MHA in hydrogel networks were investigated. The physical properties of the hydrogel were measured by SEM, Differential Scanning Calorimetry (DSC), Thermal Gravity Analysis (TGA), and a Universal Testing Machine (UTM). The cell viability of Co-MHA hydrogel was also evaluated using an in vitro MTT assay.

  2. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2017-05-01

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

  5. 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.

  6. Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum.

    PubMed

    Lee, Do Hyun; Oh, In Young; Koo, Kyo Tan; Suk, Jang Mi; Jung, Sang Wook; Park, Jin Oh; Kim, Beom Joon; Choi, Yoo Mi

    2015-02-01

    Skin aging is accompanied by wrinkle formation. At some sites, such as the periorbital skin, this is a relatively early phenomenon. We evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital wrinkles (crow's feet). In total, 23 Korean women (age range: 39-59 years), who were not pregnant, nursing, or undergoing any concurrent therapy, were enrolled in this study. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analyzed. Periorbital wrinkles were significantly improved after treatment, with improvements noted both by physician's assessment and visiometer analysis. Topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles.

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

    PubMed

    Rodriguez-Merchan, E Carlos

    2012-10-01

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

  8. Tear Film Stability in Sjögren Syndrome Patients Treated with Hyaluronic Acid Versus Crosslinked Hyaluronic Acid-Based Eye Drops.

    PubMed

    Cagini, Carlo; Torroni, Giovanni; Fiore, Tito; Cerquaglia, Alessio; Lupidi, Marco; Aragona, Pasquale; Iaccheri, Barbara

    2017-09-01

    To compare the stability of the tear film after instillation of eye drops containing hyaluronic acid (HA) or crosslinked hyaluronic acid (CLHA)-based in patients with Sjögren syndrome-related dry eye (SSDE). Forty subjects were included in this study and were divided into 2 groups: the first group (control group) consisted of 20 healthy volunteers; the second group (study group) constituted of 20 suffering from SSDE; before and 5, 30, and 60 min after instillation of eye drops the surface regularity index (SRI) and surface asymmetry index (SAI) were registered. Comparing HA and CLHA, in the control group, SAI show statistically significant difference in the time 0 and in time 5, whereas there is no a statistically significant difference after 30 and 60 min from instillation. For SRI there is no statistically significant difference at any time. In SSDE group there is no statistically significant difference in the time 0 and 5, whereas there is a statistically significant difference after 60 min for SAI, and after 30 and 60 min for SRI from instillation. Both SRI and SAI in dry eyes were significantly greater than in control eyes (P < 0.05). Our study showed a better efficacy of CLHA compared with HA in maintaining the stability of the tear film in a patient suffering from SSDE.

  9. Study of FibroTest and hyaluronic acid biological variation in healthy volunteers and comparison of serum hyaluronic acid biological variation between chronic liver diseases of different etiology and fibrotic stage using confidence intervals.

    PubMed

    Istaces, Nicolas; Gulbis, Béatrice

    2015-07-01

    Personalized ranges of liver fibrosis serum biomarkers such as FibroTest or hyaluronic acid could be used for early detection of fibrotic changes in patients with progressive chronic liver disease. Our aim was to generate reliable biological variation estimates for these two biomarkers with confidence intervals for within-subject biological variation and reference change value. Nine fasting healthy volunteers and 66 chronic liver disease patients were included. Biological variation estimates were calculated for FibroTest in healthy volunteers, and for hyaluronic acid in healthy volunteers and chronic liver disease patients stratified by etiology and liver fibrosis stage. In healthy volunteers, within-subject biological coefficient of variation (with 95% confidence intervals) and index of individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79 for hyaluronic acid, respectively. Overall hyaluronic acid within-subject biological coefficient of variation was similar among non-alcoholic fatty liver disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%), respectively, in contrast to chronic hepatitis B with 170% (140%-215%). Hyaluronic acid within-subject biological coefficients of variation were similar between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%), respectively. However, corresponding hyaluronic acid indexes of individuality were lower in the higher fibrosis stages. Non-overlapping confidence intervals of biological variation estimates allowed us to detect significant differences regarding hyaluronic acid biological variation between chronic liver disease subgroups. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. Evaluation of the efficacy and safety of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma.

    PubMed

    Ibrahim, Zeinab A; Gheida, Shereen F; El Maghraby, Gamal M; Farag, Zeinab E

    2015-06-01

    Various treatments are currently available for melasma. However, results are often disappointing. 1 To assess the efficacy and safety of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma after topical application. 2 To evaluate the dermoscopy as a tool in diagnosis and follow-up of melasma treatment. One hundred patients with mild, moderate-to-severe melasma were divided into five groups. Group I (twenty patients were treated with cream formula containing 4% hydroquinone), group II (twenty patients were treated with cream formula containing 4% hydroquinone + 10% glycolic acid), group III (twenty patients were treated with cream formula containing 4% hydroquinone + 0.01% hyaluronic acid), group IV (twenty patients were treated with cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid), and group V (twenty patients were treated with placebo cream). All patients were subjected to dermoscopic examination and digital photographs before and after treatment. The response and side effects were evaluated. Groups I, III, and IV showed highly significant changes in modified Melasma Area and Severity Index (mMASI) score after using the treatment. Group II showed significant change in mMASI score after using the treatment. The side effects were more reported in group II, followed by group IV, followed by group I, followed by group III. There was highly significant difference between the dermoscopic color findings before and after treatment. Vascularization was another dermoscopic finding. A cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid was very effective in treatment of melasma with tolerable side effects. Dermoscope is a valuable noninvasive tool in the diagnosis and follow-up of melasma treatment. © 2015 Wiley Periodicals, Inc.

  11. "Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption.

    PubMed

    Deng, Xudong; Korogiannaki, Myrto; Rastegari, Banafsheh; Zhang, Jianfeng; Chen, Mengsu; Fu, Qiang; Sheardown, Heather; Filipe, Carlos D M; Hoare, Todd

    2016-08-31

    Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification.

  12. Hyaluronic acid/chitosan multilayer coatings on neuronal implants for localized delivery of siRNA nanoplexes.

    PubMed

    Hartmann, Hanna; Hossfeld, Susanne; Schlosshauer, Burkhard; Mittnacht, Ursula; Pêgo, Ana Paula; Dauner, Martin; Doser, Michael; Stoll, Dieter; Krastev, Rumen

    2013-06-28

    Binding, stabilizing and promoting cellular uptake of siRNA are all critical efforts in creating matrices for the localized delivery of siRNA molecules to target cells. In this study, we describe the generation of chitosan imidazole/siRNA nanoplexes (NPs) embedded in nano scope polyelectrolyte multilayers (PEMs) composed of hyaluronic acid and chitosan for sustained and localized drug delivery. Regular PEM build-up, successful integration of NPs and controlled release under physiological conditions were shown. Biological efficacy was evaluated in neuronal cell culture concerning cell adhesion, viability, NPs uptake and gene silencing. The additionally shown biological functionalization of neuronal implants possesses potential for future applications in the field of regenerative medicine and treatment of spinal cord injuries.

  13. Growth factors-loaded stents modified with hyaluronic acid and heparin for induction of rapid and tight re-endothelialization.

    PubMed

    Choi, Dong Hoon; Kang, Sung Nam; Kim, Seong Min; Gobaa, Samy; Park, Bang Ju; Kim, Ik Hwan; Joung, Yoon Ki; Han, Dong Keun

    2016-05-01

    Rapid re-endothelialization of damaged vessel lining efficiently prevents restenosis and thrombosis and restores original vascular functions. In this study, we designed a novel metallic stent with a heparin-modified surface and used different methods, including 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and divinyl sulfone (DVS), to load growth factors. First we loaded heparin into a dopamine-conjugated hyaluronic acid (HA) coating to serve as a growth factor reservoir. In a second step, we took advantage of the heparin-binding domain of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) to gain advanced re-endothelialization capabilities. We demonstrated that DVS technique offered higher amount of growth factor loading. In vitro assessment also showed better capillary-like structure formation and localized gap junctions when DVS coating was employed. This study suggested that growth factor loaded stent modified by HA and heparin provided the advantage to rapid and tight restoration of endothelium.

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

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

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

    PubMed

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

    2015-01-01

    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. 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. 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. 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 I.

  16. High biological variation of serum hyaluronic acid and Hepascore, a biochemical marker model for the prediction of liver fibrosis.

    PubMed

    Rossi, Enrico; Adams, Leon A; Ching, Helena L; Bulsara, Max; MacQuillan, Gerry C; Jeffrey, Gary P

    2013-05-01

    Serum hyaluronic acid and biochemical models which require hyaluronic acid analysis are commonly used as predictors of liver fibrosis in patients with chronic liver disease, however biological variation data for hyaluronic acid are deficient. Four serial serum samples were obtained at weekly intervals from healthy volunteers and patients with chronic hepatitis B, chronic hepatitis C and non- alcoholic fatty liver disease (NAFLD; 20 in each group). The within-individual week-to-week variation (CVI) and reference change values for hyaluronic acid, α₂-macroglobulin and Hepascore were obtained. Hepascore is calculated from hyaluronic acid, α2-macroglobulin, bilirubin and γ-glutamyltransferase activity. Hyaluronic acid displayed large within-individual variation, the CVI values were 62% in healthy subjects, 38% in hepatitis C, 37% in hepatitis B and 36% in NAFLD patients. Hepascore CVIs were 43% in healthy subjects, 24% in hepatitis C, 28% in hepatitis B and 39% in NAFLD patients. α₂-Macroglobulin was much less variable with CVIs ranging from 4.4% to 7.6%. Bland-Altman plots of week-to-week variations showed rates of significant disagreement for samples collected in any 2 successive weeks varied from 5% in NAFLD patients to 8.3% in healthy subjects. When using non-fasting serum samples, hyaluronic acid and to a lesser extent, the Hepascore model display large within-individual variations in both health and chronic liver disease. This information is critical for interpreting the significance of both single measurements and changes in serial measurements.

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

    PubMed

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

    2014-08-25

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

  18. The reaction of hyaluronic acid and its monomers, glucuronic acid and N-acetylglucosamine, with reactive oxygen species.

    PubMed

    Jahn, M; Baynes, J W; Spiteller, G

    1999-10-15

    Synovial fluid is a approximately 0.15% (w/v) aqueous solution of hyaluronic acid (HA), a polysaccharide consisting of alternating units of GlcA and GlcNAc. In synovial fluid of patients suffering from rheumatoid arthritis, HA is thought to be degraded either by radicals generated by Fenton chemistry (Fe2+/H2O2) or by NaOCl generated by myeloperoxidase. We investigated the course of model reactions of these two reactants in physiological buffer with HA, and with the corresponding monomers GlcA and GlcNAc. meso-Tartaric acid, arabinuronic acid, arabinaric acid and glucaric acid were identified by GC-MS as oxidation products of glucuronic acid. When GlcNAc was oxidised, erythronic acid, arabinonic acid, 2-acetamido-2-deoxy-gluconic acid, glyceric acid, erythrose and arabinose were formed. NaOCl oxidation of HA yielded meso-tartaric acid; in addition, arabinaric acid and glucaric acid were obtained by oxidation with Fe2+/H2O2. These results indicate that oxidative degradation of HA proceeds primarily at glucuronic acid residues. meso-Tartaric acid may be a useful biomarker of hyaluronate oxidation since it is produced by both NaOCl and Fenton chemistry.

  19. Hyaluronic acid increases tendon derived cell viability and collagen type I expression in vitro: Comparative study of four different Hyaluronic acid preparations by molecular weight.

    PubMed

    Osti, Leonardo; Berardocco, Martina; di Giacomo, Viviana; Di Bernardo, Graziella; Oliva, Francesco; Berardi, Anna C

    2015-10-06

    Hyaluronic Acid (HA) has been already approved by Food and Drug Administration (FDA) for osteoarthritis (OA), while its use in the treatment of tendinopathy is still debated. The aim of this study was to evaluate in human rotator cuff tendon derived cells the effects of four different HA on cell viability, proliferation, apoptosis and the expression of collagen type I and collagen type III. An in vitro model was developed on human tendon derived cells from rotator cuff tears to study the effects of four different HA preparations (Ps) (sodium hyaluronate MW: 500-730 KDa - Hyalgan®, 1000 kDa Artrosulfur HA®, 1600 KDa Hyalubrix® and 2200 KDa Synolis-VA®) at various concentrations. Tendon derived cells morphology were evaluated after 0, 7 and 14 d of culture. Viability, proliferation, apoptosis were evaluated after 0, 24 and 48 h of culture. The expression and deposition of collagen type I and collagen type III were evaluated after 1, 7 and 14 d of culture. All HAPs tested increased viability and proliferation, in dose dependent manner. HAPs already reduce apoptosis at 24 h compared to control cells (without HAPs). Furthermore, HAPs stimulated the synthesis of collagen type I in a dose dependent fashion over 14 d, without increase in collagen type III; moreover, in the presence of Synolis-VA® the expression and deposition of collagen type I was significantly higher as compare with the other HAPs. HAPs enhanced viability, proliferation and expression of collagen type I in tendon derived cells.

  20. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review.

    PubMed

    Altman, R D; Manjoo, A; Fierlinger, A; Niazi, F; Nicholls, M

    2015-10-26

    Knee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. A variety of mechanisms in which HA is thought to combat knee OA are reported in the current basic literature. We conducted a comprehensive literature search to identify currently available primary non-clinical basic science articles focussing on the mechanism of action of IA-HA treatment. Included articles were assessed and categorized based on the mechanism of action described within them. The key findings and conclusions from each included article were obtained and analyzed in aggregate with studies of the same categorical assignment. Chondroprotection was the most frequent mechanism reported within the included articles, followed by proteoglycan and glycosaminoglycan synthesis, anti-inflammatory, mechanical, subchondral, and analgesic actions. HA-cluster of differentiation 44 (CD44) receptor binding was the most frequently reported biological cause of the mechanisms presented. High molecular weight HA was seen to be superior to lower molecular weight HA products. HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products. The non-clinical basic science literature provides evidence for numerous mechanisms in which HA acts on joint structures and function. These actions provide support for the purported clinical benefit of IA-HA in OA of the knee. Future research should not only focus on the pain relief provided by IA-HA treatment, but the disease modification properties that this treatment modality possesses as well.

  1. Multivalent hyaluronic acid bioconjugates improve sFlt-1 activity in vitro.

    PubMed

    Altiok, Eda I; Santiago-Ortiz, Jorge L; Svedlund, Felicia L; Zbinden, Aline; Jha, Amit K; Bhatnagar, Deepika; Loskill, Peter; Jackson, Wesley M; Schaffer, David V; Healy, Kevin E

    2016-07-01

    Anti-VEGF drugs that are used in conjunction with laser ablation to treat patients with diabetic retinopathy suffer from short half-lives in the vitreous of the eye resulting in the need for frequent intravitreal injections. To improve the intravitreal half-life of anti-VEGF drugs, such as the VEGF decoy receptor sFlt-1, we developed multivalent bioconjugates of sFlt-1 grafted to linear hyaluronic acid (HyA) chains termed mvsFlt. Using size exclusion chromatography with multiangle light scattering (SEC-MALS), SDS-PAGE, and dynamic light scattering (DLS), we characterized the mvsFlt with a focus on the molecular weight contribution of protein and HyA components to the overall bioconjugate size. We found that mvsFlt activity was independent of HyA conjugation using a sandwich ELISA and in vitro angiogenesis assays including cell survival, migration and tube formation. Using an in vitro model of the vitreous with crosslinked HyA gels, we demonstrated that larger mvsFlt bioconjugates showed slowed release and mobility in these hydrogels compared to low molecular weight mvsFlt and unconjugated sFlt-1. Finally, we used an enzyme specific to sFlt-1 to show that conjugation to HyA shields sFlt-1 from protein degradation. Taken together, our findings suggest that mvsFlt bioconjugates retain VEGF binding affinity, shield sFlt-1 from enzymatic degradation, and their movement in hydrogel networks (in vitro model of the vitreous) is controlled by both bioconjugate size and hydrogel network mesh size. These results suggest that a strategy of multivalent conjugation could substantially improve drug residence time in the eye and potentially improve therapeutics for the treatment of diabetic retinopathy.

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

    PubMed

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

    2011-09-27

    Macromolecular conjugates of a natural polysaccharide, hyaluronic acid, with diethylenetriaminepentaacetic acid (DTPA)-metal complexes were synthesized and characterized by FTIR, NMR, SEC-MALLS and ICP analysis. Several parameters of the cross-linking reaction as molecular weight of starting HA, temperature, equivalent of DTPA bis-anhydride, concentration of HA, presence of transacylation catalyst DMAP and reaction time were studied. The mechanism for the reaction was suggested and relationship between the molecular weight assigned by SEC-MALLS, reaction parameters and rheological properties of the final cross-linked products were investigated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Hyaluronic acid stimulates the formation of calcium phosphate on CoCrMo alloy in simulated physiological solution.

    PubMed

    Milošev, Ingrid; Hmeljak, Julija; Cör, Andrej

    2013-03-01

    The behaviour of CoCrMo alloy has been studied in two simulated physiological solutions-NaCl and Hanks' solutions-each containing the sodium salt of hyaluronic acid. Hyaluronic acid is a component of synovial joint fluid, so the behaviour of orthopaedic alloys in its presence needs to be assessed. Electrochemical methods, X-ray photoelectron spectroscopy and scanning electron microscopy have been used to analyse the composition, thickness and morphology of any layers formed on the alloy. The addition of hyaluronic acid shifts the corrosion potential and increases the value of polarization resistance. The presence of hyaluronic acid in simulated Hanks' physiological solution stimulates the formation of a calcium phosphate layer, opening up the possibility for tailoring the surface properties of CoCrMo alloy. The viability of human osteoblast-like was determined using the Alamar(®) Blue Assay, while the osteogenic activity was evaluated by alkaline phosphatase activity. The presence of hyaluronic acid affects the alkaline phosphatase activity.

  4. The cross-linked biopolymer hyaluronic acid as an artificial vitreous substitute.

    PubMed

    Schramm, Charlotte; Spitzer, Martin S; Henke-Fahle, Sigrid; Steinmetz, Gabriele; Januschowski, Kai; Heiduschka, Peter; Geis-Gerstorfer, Jürgen; Biedermann, Tilo; Bartz-Schmidt, Karl U; Szurman, Peter

    2012-02-02

    Biopolymers are promising substances in the development of a new vitreous substitute to overcome the drawbacks associated with current hydrophobic tamponade materials. Different hydrogels were assembled by cross-linking hyaluronic acid either with adipic dihydrazide (ADH) by carboxylation with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCI) after hydrazation or by photocrosslinking with UV-light and N-vinyl-pyrrolidinone. The refractive index and rheologic properties of the obtained gels were investigated. To quantify the degradation of the hydrogels over time, free hyaluronic acid was measured photometrically by means of the degradation product uronic acid. For biocompatibility testing, the hydrogels were applied on top of cultured retinal pigment epithelial (RPE) cells and analyzed by the cell viability, MTT, and alamar blue viability cytotoxicity assays and flow cytometry, with Annexin V-FITC and propidium iodide co-staining. The in vivo biocompatibility of the hydrogels was tested in vitrectomized rabbit eyes for up to 6 weeks. The synthesized hydrogels were all clear and transparent and had a refractive index similar to human vitreous. The rheologic measurements suggested sufficient viscosity and elasticity for intraocular use. Quantification of the degradation products revealed only a small decay of the gels over 1 month. However, the ADH cross-linked hydrogels induced mild cytotoxicity in the RPE cells. The UV cross-linked hydrogels showed no toxicity or induction of apoptosis. In vivo the UV cross-linked biogels remained in place for 6 weeks, and electrophysiology and histology showed excellent tissue biocompatibility. Biopolymers based on UV cross-linked hyaluronic acid may be promising vitreous substitutes.

  5. Acid mucopolysaccharide metabolism in leprosy. 2. Subcellular localization of hyaluronic acid and beta-glucuronidase in leprous infiltrates suggestive of a host-Mycobacterium leprae metabolic relationship.

    PubMed

    Matsuo, E; Skinsnes, O K

    1974-01-01

    Electron- and light microscopic analyses were conducted on leprosy skin biopsies relative to the origin of hyaluronic acid, which has previously been observed to be distributed inversely in ratio to the degree of cell- mediated immunity. The present study investigated the subcellular localization of hyaluronic acid and its degrading enzyme in various types of leprosy. Hyaluronic acid in some lepromatous leprosy cases was shown to be accumulated in the limiting membranes of the phagosomes of lepra cells and Myco-bacteria leprae have beta-glucuronidase which plays a role in the degradation of hyaluronic acid. Contrariwise, in tuberculoid leprosy, beta-glucuronidase was detected in the lysosomes of epithelioid cells and giant cells. This result suggests that the origin of hyaluronic acid is in histiocytes and at the same time it might suggest that M. leprae is in competition with enzymes of epithelioid cells for hyaluronic acid, whereas reduced or absent beta-glucuronidase in lepra cells enable bacilli to utilize the AMPS as a nutrient.

  6. Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease.

    PubMed

    Lee, David; Lu, Qiaozhi; Sommerfeld, Sven D; Chan, Amanda; Menon, Nikhil G; Schmidt, Tannin A; Elisseeff, Jennifer H; Singh, Anirudha

    2017-06-01

    Hyaluronic acid (HA) solutions effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms. However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation. Conversely, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Here, we developed an HA-eye drop formulation that selectively binds and retains HA for extended periods of time on the ocular surface. We synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binding either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. HA solution was mixed with the polymer-peptide system and tested on both ex vivo and in vivo models to determine its ability to prolong HA retention. Furthermore, rabbit ocular surface tissues treated with binding peptides and HA solutions demonstrated superior lubrication with reduced kinetic friction coefficients compared to tissues treated with conventional HA solution. The results suggest that binding peptide-based solution can keep the ocular surface enriched with HA for prolonged times as well as keep it lubricated. Therefore, this system can be further developed into a more effective treatment for dry eye patients than a standard HA eye drop. Eye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a

  7. Receptor-Meditated Endocytosis by Hyaluronic Acid@Superparamagnetic Nanovetor for Targeting of CD44-Overexpressing Tumor Cells

    PubMed Central

    Yu, Kwang Sik; Lin, Meng Meng; Lee, Hyun-Ju; Tae, Ki-Sik; Kang, Bo-Sun; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Han, Seung-Yun; Kim, Do Kyung

    2016-01-01

    The present report proposes a more rational hyaluronic acid (HA) conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs) by covalently binding the targeting molecules (HA) with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA)@SPIONs was included oxidization of nanoparticle’s surface with H2O2 followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells. Fourier transform infrared (FTIR) and zeta-potential studies confirmed the chemical bonding between amino acid linker and polysaccharides. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed that HA-SPIONs-treated cells remained 82.9% ± 2.7% alive at high particle dosage (200 µg/mL iron concentration), whereas GA-SPIONs and bare SPIONs (B-SPIONs) treated cells had only 59.3% ± 13.4% and 26.5% ± 3.1% survival rate at the same conditions, respectively. Confocal microscopy analysis showed increased cellular internalization of HA-SPIONs compared to non-interacting agarose coated SPIONs (AgA-SPIONs). PMID:28335277

  8. Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis.

    PubMed

    Reichenbach, Stephan; Blank, Sacha; Rutjes, Anne W S; Shang, Aijing; King, Elizabeth A; Dieppe, Paul A; Jüni, Peter; Trelle, Sven

    2007-12-15

    To compare the effectiveness and safety of intraarticular high-molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee. We performed a systematic review and meta-analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random-effects meta-analysis. Thirteen trials with a pooled total of 2,085 patients contributed to the meta-analysis. The pooled effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent-to-treat analysis had pooled effect sizes near null. The meta-analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) = 0%). Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

  9. Hyaluronic acid based hydrogel system for soft tissue regeneration and drug delivery

    NASA Astrophysics Data System (ADS)

    Jha, Amit Kumar

    We have developed hyaluronic acid (HA)-based, biomimetic hydrogel matrices that are hierarchically structured, mechanically robust and biologically active. Specifically, HA-based hydrogel particles (HGPs) with controlled sizes, defined porosity, and improved stability were synthesized using different inverse emulsion systems and crosslinking chemistries. The resultant particles either contained residual functional groups or were rendered reactive by subsequent chemical modifications. HA-based doubly crosslinked networks (DXNs) were synthesized via covalent crosslinking of HA HGPs with soluble HA macromers carrying mutually reactive functional groups. These hybrid matrices are hierarchical in nature, consisting of densely crosslinked HGPs integrated in a loosely connected secondary matrix. Their mechanical properties and degradation kinetics can be readily tuned by varying the particle size, functional group density, intra- and interparticle crosslinking. To improve the biological functions of HA HGPs, perlecan domain I (PlnDI), a basement membrane proteoglycan that has strong affinity for various heparin binding growth factors (HBGFs), was successfully conjugated to the particles through the core protein via a flexible poly(ethylene glycol) (PEG) linker. The immobilized PlnDI maintains its ability to bind bone morphogenetic proteins (BMP-2) and modulates its in vitro release. A similar, sustained release of BMP-2 was achieved by encapsulating BMP-2-loaded HGPs within a photocrosslinked HA matrix. When encapsulated in HA DXNs, primary bovine chondrocytes were able to maintain their phenotype, proliferate readily and produce abundant glycosaminoglycan. Finally, cell-adhesive HA DXNs were fabricated by encapsulating gelatin-decorated HA HGPs in a secondary HA matrix. Human MSCs were shown to adhere to the composite matrix through the focal adhesion sites clustered on particle surface. The cell-adhesive composite matrices supported hMSC proliferation and migration into

  10. Nasal alar necrosis following hyaluronic Acid injection into nasolabial folds: a case report.

    PubMed

    Manafi, Ali; Barikbin, Behrooz; Manafi, Amir; Hamedi, Zahra Sadat; Ahmadi Moghadam, Shokoofeh

    2015-01-01

    Injection of synthetic fillers for soft tissue augmentation is increasing over the last decade. One of the most common materials used is hyaluronic acid (HA) that is safe and temporary filler for soft tissue augmentation. We present a case of 54-year-old female who experienced vascular occlusion and nasal alar necrosis following HA injection to the nasolabial folds. She suffered from pain, necrosis, infection, and alar loss that finally required a reconstructive surgery for cosmetic appearance of the nose. The case highlights the importance of proper injection technique by an anesthesiologist, as well as the need for immediate recognition and treatment of vascular occlusion.

  11. Nasal Alar Necrosis Following Hyaluronic Acid Injection into Nasolabial Folds: A Case Report

    PubMed Central

    Manafi, Ali; Barikbin, Behrooz; Manafi, Amir; Hamedi, Zahra Sadat; Ahmadi Moghadam, Shokoofeh

    2015-01-01

    Injection of synthetic fillers for soft tissue augmentation is increasing over the last decade. One of the most common materials used is hyaluronic acid (HA) that is safe and temporary filler for soft tissue augmentation. We present a case of 54-year-old female who experienced vascular occlusion and nasal alar necrosis following HA injection to the nasolabial folds. She suffered from pain, necrosis, infection, and alar loss that finally required a reconstructive surgery for cosmetic appearance of the nose. The case highlights the importance of proper injection technique by an anesthesiologist, as well as the need for immediate recognition and treatment of vascular occlusion. PMID:25606480

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

    PubMed

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

    2016-04-01

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

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid.

    PubMed

    Altman, Roy D; Schemitsch, Emil; Bedi, Asheesh

    2015-10-01

    Clinical practice guidelines are of increasing importance in the decision making for the treatment of knee osteoarthritis. Inconsistent recommendations regarding the use of intra-articular hyaluronic acid for the treatment of knee osteoarthritis have led to confusion among treating physicians. Literature search to identify clinical practice guidelines that provide recommendations regarding the use of intra-articular hyaluronic acid treatment for knee osteoarthritis was conducted. Included guidelines were appraised using the AGREE II instrument. Guideline development methodologies, how the results were assessed, the recommendation formation, and work group composition were summarized. Overall, 10 clinical practice guidelines were identified that met our inclusion criteria. AGREE II domain scores were variable across the included guidelines. The methodology utilized across the guidelines was heterogeneous regarding the evidence inclusion criteria, analysis of evidence results, formulation of clinical practice recommendations, and work group composition. The recommendations provided by the guidelines for intra-articular hyaluronic acid treatment for knee osteoarthritis are highly inconsistent as a result of the variability in guideline methodology. Overall, 30% of the included guidelines recommended against the use of intra-articular hyaluronic acid in the treatment of knee osteoarthritis, while 30% deemed the treatment an appropriate intervention under certain scenarios. The remaining 40% of the guidelines provided either an uncertain recommendation or no recommendation at all, based on the high variability in reviewed evidence regarding efficacy and trial quality. There is a need for a standard "appropriate methodology" that is agreed upon for osteoarthritis clinical practice guidelines in order to prevent the development of conflicting recommendations for intra-articular hyaluronic acid treatment for knee osteoarthritis, and to assure that treating physicians who

  18. Surface modification of model hydrogel contact lenses with hyaluronic acid via thiol-ene "click" chemistry for enhancing surface characteristics.

    PubMed

    Korogiannaki, Myrto; Zhang, Jianfeng; Sheardown, Heather

    2017-10-01

    Discontinuation of contact lens wear as a result of ocular dryness and discomfort is extremely common; as many as 26% of contact lens wearers discontinue use within the first year. While patients are generally satisfied with conventional hydrogel lenses, improving on-eye comfort continues to remain a goal. Surface modification with a biomimetic, ocular friendly hydrophilic layer of a wetting agent is hypothesized to improve the interfacial interactions of the contact lens with the ocular surface. In this work, the synthesis and characterization of poly(2-hydroxyethyl methacrylate) surfaces grafted with a hydrophilic layer of hyaluronic acid are described. The immobilization reaction involved the covalent attachment of thiolated hyaluronic acid (20 kDa) on acrylated poly(2-hydroxyethyl methacrylate) via nucleophile-initiated Michael addition thiol-ene "click" chemistry. The surface chemistry of the modified surfaces was analyzed by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy. The appearance of N (1s) and S (2p) peaks on the low resolution X-ray photoelectron spectroscopy spectra confirmed successful immobilization of hyaluronic acid. Grafting hyaluronic acid to the poly(2-hydroxyethyl methacrylate) surfaces decreased the contact angle, the dehydration rate, and the amount of nonspecific sorption of lysozyme and albumin in comparison to pristine hydrogel materials, suggesting the development of more wettable surfaces with improved water-retentive and antifouling properties, while maintaining optical transparency (>92%). In vitro testing also showed excellent viability of human corneal epithelial cells with the hyaluronic acid-grafted poly(2-hydroxyethyl methacrylate) surfaces. Hence, surface modification with hyaluronic acid via thiol-ene "click" chemistry could be useful in improving contact lens surface properties, potentially alleviating symptoms of contact lens related dryness and discomfort during

  19. 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.

  20. 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.

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

    PubMed

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

    2007-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    Ondeck, Matthew G.; Engler, Adam J.

    2016-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Di Giacomo, G; De Gasperis, N

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. 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.

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

    PubMed

    Schuster, Bernd

    2015-06-01

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

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

    PubMed

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

    1994-09-01

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

  12. Hyaluronic acid-based medical device and oral disorders: can it be used in paediatric dentistry?

    PubMed

    D'Ercole, S; Nanussi, A; Tieri, M; Barattini, D F; Tripodi, D

    2015-01-01

    Due to its physical and biological characteristics and safety profile, hyaluronic acid is very widely used in numerous clinical conditions, ranging from its best-known use in cosmetic surgery (as a filler and for its ability to promote tissue regeneration and therefore minimise scarring) to lesser-known fields such as ophthalmic surgery, major abdominal surgery (where it is used to prevent the complication of adhesion bands) and intra-articular use. Studies were recently published in which this type of device was also used in paediatric patients for the management of inflammatory disorders of the oral cavity and teething symptoms. As this is a highly topical field for dentists, we felt it would be useful to review the efficacy and safety of the device in the paediatric population treated, and analyse any discrepancies with the results obtained in the adult population. The preparations of hyaluronic acid used in pediatric dentistry, thanks to their anti-inflammatory and angiogenic properties, proved to be very effective in therapy of oral diseases in children. Further clinical research is needed to confirm the effectiveness of these products to dispel doubts about any side effects.

  13. Correction of midface volume deficiency using hyaluronic acid filler and intradermal radiofrequency.

    PubMed

    Ko, Eun Jung; Kim, Hyuk; Park, Won-Seok; Kim, Beom Joon

    2015-02-01

    Hyaluronic acid (HA) fillers are increasingly used for midface augmentation, which can be performed for facial rejuvenation. Previous study proved that radiofrequency (RF) treatment prior to HA filler injection may provide synergistic and long-lasting effects for the reduction of nasolabial fold wrinkles. Here, we report a case in which the efficacy of two different treatments using RF and HA filler and HA filler alone was assessed using a split-face design. In conclusion, the intradermal needle RF with HA filler may be a more safe and effective method than HA filler alone for correcting midface volume deficit. Appropriate volume loss replacement should correct the flattening and furrowing of the central area of the mid-cheek, which is a consequence of the aging process. Also, it will provide a more youthful appearance. Hyaluronic acid (HA) fillers are an established intervention for correcting facial volume deficiency. In a previous study ( 1 ), radiofrequency (RF) was used to overcome the short duration of HA fillers and resulted in a good outcome.

  14. Skin Remodeling Using Hyaluronic Acid Filler Injections in Photo-Aged Faces.

    PubMed

    França Wanick, Fabiana Braga; Almeida Issa, Maria Claudia; Luiz, Ronir Raggio; Soares Filho, Porphirio José; Olej, Beni

    2016-03-01

    Hyaluronic acid (HA) filler is an important dermatological procedure. Although many studies have reported clinical improvement with this procedure, histology with morphometric evidence is not well documented. To evaluate the clinical and histological results of a HA filler injection and to quantify dermis remodeling at 3 and 9 months after HA injections into aged faces. Twenty patients were enrolled in this study. Hyaluronic acid filler was injected into the nasolabial folds and preauricular regions of the patients. Skin biopsies of the preauricular regions were performed before the procedure and at 3 and 9 months after the procedure. Sixteen women (aged 40-50 years) completed the clinical study and demonstrated improvement for 12 months. Twenty patients completed the histologic studies. Morphologic evaluation showed increases in the epidermal layers. The morphometric study showed a statistically significant increase in collagen fibers at 3 and 9 months after the procedure (34.2% ± 31.5% and 39.5% ± 39.7%, respectively, p < .05). Sustained clinical results for HA filler can be explained not only by the presence of HA gel on the dermis but also by the dermal remodeling induced by HA filler injected into the face.

  15. Spray-assisted layer-by-layer assembly on hyaluronic acid scaffolds for skin tissue engineering.

    PubMed

    Monteiro, Isa P; Shukla, Anita; Marques, Alexandra P; Reis, Rui L; Hammond, Paula T

    2015-01-01

    Tissue engineering approaches for the development of a single epidermal-dermal scaffold to treat full-thickness skin defects have been limited by difficulties in the fabrication of a bilayer scaffold combining the specific properties of the epidermis and the dermis. Here we present an innovative approach to developing a scaffold that holds promise for skin tissue engineering. We utilize the spray-assisted layer-by-layer assembly technique to deposit a polyelectrolyte multilayer film composed of hyaluronic acid and poly-L-lysine (the epidermal component) on a porous hyaluronic acid scaffold (the dermal component), in a rapid and controlled manner. The multilayer film promotes cell adhesion, contributing to regeneration of the epidermal barrier functions of skin. While human keratinocytes attached and proliferated on the coated porous scaffolds, they did not invade the porous dermal component, thus leaving room for seeding of relevant fibroblast cell types in this scaffold. This scaffold therefore holds promise for co-culture of different cells, which may be useful for treatment of full-thickness skin defects as well as other tissue engineering applications. © 2014 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2010-01-01

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

  17. [Effects of extracts of Dragon's blood on fibroblast proliferation and extracellular matrix hyaluronic acid].

    PubMed

    Li, Dan; Hui, Rui; Hu, Yongwu; Han, Yan; Guo, Shuzhong

    2015-01-01

    To investigate the effects of Dragon' s blood extract on proliferation and secret extracellular matrix function of fibroblasts in vitro. Dragon' s blood was extracted by chloroform, acetoacetic ester, alcohol. Human fibroblast were cultured in vitro in media containing gradient dilutions of Dragon' s blood extracts (0.002, 0.02, 0.2, 2, 20 mg/ml) , which was followed by cell proliferation assessed with MTT assay on 0, 12, 24, 36, 48, 60, 72 h. Under the optimal concentration, the cell growth curves were drawn and the flow cytometry (FCM) was used to determine the changes of cell cycle. On 0, 12, 24, 36, 48, 60, 72 h, the concentration of hyaluronic acid in the supernatant of fibroblast culture was measured by radioimmunoassay. 0.2-2 mg/ml Dragon' s blood extracts enhanced the proliferation of fibroblasts in a dose-dependent manner. 2 mg/ml was the optimal dilution of Dragon's blood extract, and it increased the ratio of S cells in cell cycle [(25.80 ± 3.10)%] than control group [(7.50 ± 0.70)%, P < 0.01]. From 12 h to 72 h, in 2 mg/ml Dragon's blood group, concentration of Hyaluronic acid secreted by fibroblasts gradually increased, but were less than control (P < 0.01). Dragon's blood acetoacetic ester extract improved the proliferation of cultured human fibroblasts in vitro, might be beneficial to promote wound healing.

  18. Consensus Recommendations for Optimal Augmentation of the Asian Face with Hyaluronic Acid and Calcium Hydroxylapatite Fillers.

    PubMed

    Rho, Nark-Kyoung; Chang, Yao-Yuan; Chao, Yates Yen-Yu; Furuyama, Nobutaka; Huang, Peter Y C; Kerscher, Martina; Kim, Hee-Jin; Park, Je-Young; Peng, Hsien Li Peter; Rummaneethorn, Paisal; Rzany, Berthold; Sundaram, Hema; Wong, Chin Ho; Yang, Yuli; Prasetyo, Adri Dwi

    2015-11-01

    Although the use of filling agents for soft-tissue augmentation has increased worldwide, most consensus statements do not distinguish between ethnic populations. There are, however, significant differences between Caucasian and Asian faces, reflecting not only cultural disparities, but also distinctive treatment goals. Unlike aesthetic patients in the West, who usually seek to improve the signs of aging, Asian patients are younger and request a broader range of indications. Members of the Asia-Pacific Consensus group-comprising specialists from the fields of dermatology, plastic surgery, anatomy, and clinical epidemiology-convened to develop consensus recommendations for Asians based on their own experience using cohesive polydensified matrix, hyaluronic acid, and calcium hydroxylapatite fillers. The Asian face demonstrates differences in facial structure and cosmetic ideals. Improving the forward projection of the "T zone" (i.e., forehead, nose, cheeks, and chin) forms the basis of a safe and effective panfacial approach to the Asian face. Successful augmentation may be achieved with both (1) high- and low-viscosity cohesive polydensified matrix/hyaluronic acid and (2) calcium hydroxylapatite for most indications, although some constraints apply. The Asia-Pacific Consensus recommendations are the first developed specifically for the use of fillers in Asian populations. Therapeutic, V.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2013-10-17

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

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

    PubMed Central

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

    2013-01-01

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

  2. Injectable In Situ Forming Biodegradable Chitosan-Hyaluronic acid Based Hydrogels for Cartilage Tissue Engineering

    PubMed Central

    Tan, Huaping; Chu, Constance R.; Payne, Karin; Marra, Kacey G.

    2009-01-01

    Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAG). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications. PMID:19167750

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

    PubMed

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

    2016-01-11

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

  4. Laryngoplasty with hyaluronic acid in patients with unilateral vocal fold paralysis.

    PubMed

    Reiter, Rudolf; Rudolf, Reiter; Brosch, Sibylle; Sibylle, Brosch

    2012-11-01

    Augmentation of vocal fold with hyaluronic acid (Restylane; Q-Med AB, Uppsala, Sweden) is used as a therapeutic option for insufficient glottic closure in unilateral vocal fold paralysis (UVP). Analysis of the optimal glottic width, effectiveness (long-term voice improvement as a consequence of longevity of Restylane), and safety of this new method was made. In a prospective clinical cohort study, 19 consecutive patients with UVP who received vocal fold augmentation with hyaluronic acid (Restylane) were examined preoperatively; 6 weeks, 6, and 12 months postoperatively by laryngostroboscopy; and their voice was evaluated by subjective, objective, and self-assessment (Voice Handicap Index). In 11 of 19 (58%) patients, a subjectively and objectively acceptable voice quality was observed in a follow-up of 12 months. Eight of 19 (42%) patients had a considerable impairment of the voice after 6 weeks (range: 1-24 weeks). Therefore, another intervention (eg, injection laryngoplasty or thyroplasty) was recommended. An impairment of voice was mainly observed if the preoperative glottal gap during phonation was more than 1 mm. A long duration (up to 12 months) of acceptable quality of voice was achieved by augmentation with Restylane, if the glottal gap was 1 mm or less videolaryngostroboscopically during phonation. The authors recommend this therapy for temporary voice improvement and to augment vocal therapy, if spontaneous recovery of voice is likely. Long-term results remain to be seen. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Hyaluronic acid conjugation facilitates clearance of intracellular bacterial infections by streptomycin with neglectable nephrotoxicity.

    PubMed

    Qiu, Yuanhao; Hou, Yilin; Sun, Feifei; Chen, Peng; Wang, Dongdong; Mu, Haibo; Zhang, Xiaoli; Ding, Kan; Duan, Jinyou

    2017-09-01

    Antibiotics such as β-lactams and aminoglycosides are often subtherapeutic to intracellular infections due to their high hydrophilicity, resulting in low effectiveness against intracellular pathogens and the emergence of antibiotic resistance. Here we reported that an endogenous aminoglycan, hyaluronic acid could be an effective carbohydrate carrier of the aminoglycoside antibiotic, streptomycin against intracellular pathogens. This conjugation could enhance phagocytic activity, and facilitated the entry of streptomycin into host cells via a CD44-mediated pathway. It appeared that this conjugate could clear intracellular bacteria in phagocytic or nonphagocytic cells in a short-term therapy (4 h) at a lower effective dose. In addition, this conjugate was more efficient in reducing bacteria burden in an in vivo acute infection model than streptomycin did. Interestingly, subcutaneous injection of this conjugate at an excess amount had undetectable side effects such as nephrotoxicity. These results suggested that hyaluronic acid might be an efficient Trojan horse for the delivery of hydrophilic antibiotics to deal with intracellular infections. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Aggarwal, Anita; Sempowski, Ian P.

    2004-01-01

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

  10. Correction of Age-Related Midface Volume Loss With Low-Volume Hyaluronic Acid Filler.

    PubMed

    Wilson, Monique Vanaman; Fabi, Sabrina Guillen; Greene, Ryan

    2017-03-01

    The pivotal approval trial for a smooth, highly cohesive, viscous, 20-mg/mL hyaluronic acid filler demonstrated sustained aesthetic improvement, with a mean injection volume of 6.65 mL. In daily practice, however, it is not often practical or necessary to use large injection volumes to achieve the desired cosmetic outcome. To assess the efficacy, longevity, and patient satisfaction associated with correction of age-related midface volume loss using the low volumes of hyaluronic acid filler more commonly used in day-to-day practice. A 2-center, retrospective cohort study examined medical records of 61 healthy patients who underwent treatment for facial volume loss with hyaluronic acid filler from November 1, 2013, through April 31, 2014. Follow-up visits were conducted at 1, 3, 6, and 12 months after the procedure. Data were pooled from a private facial plastic surgery practice in Weston, Florida, and a private cosmetic dermatology practice in San Diego, California. Patients were treated with hyaluronic acid filler according to the investigator's usual practices. The main outcome measure was patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment. Scores range from 1 to 5; 1 indicates very much improved and 5, worse. A total of 61 consecutive, healthy adult patients (mean [SD] age, 57.4 [12.8] years) with mild to severe facial volume loss were enrolled in the study. A total of 46 patients (75%) were white, 3 (5%) were black/African American, 9 (15%) were Hispanic/Latino, 1 (2%) was Asian/Pacific Islander, and 2 (3%) were other. Three patients (5%) were male, and 58 (95%) were female. Mean initial treatment volume was 1.6 mL. At follow-up, 29 patients (48%) elected to have a touch-up treatment; mean total touch-up volume was 1.4 mL. The patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment demonstrated that 73% (41 of 56) to 89% (24 of 27) of the study patients reported being very

  11. Evaluation of hyaluronic acid intra-articular injections in the treatment of primary and secondary osteoarthritis of the knee.

    PubMed

    Swięchowicz, Sławomir; Ostałowska, Alina; Kasperczyk, Aleksandra; Nowak, Dariusz; Birkner, Ewa; Kasperczyk, Sławomir

    2012-10-22

    Osteoarthritis is one of the most common locomotor conditions and the knee is the second most frequently affected articulation. One of therapeutic methods is viscosupplementation involving intra-articular injections of hyaluronic acid preparations. The aim of the study was to evaluate the clinical status and analyse selected biochemical blood parameters in patients with knee osteoarthritis after intra-articular injections of a hyaluronic acid preparation. Blood was taken from 113 patients, 60 patients with primary and 53 patients with secondary osteoarthritis, who were administered intra-articular injections of a hyaluronic acid preparation into the affected knee, according to the schedule established in the study protocol. Concentration of lipid hydroperoxides in blood plasma was determined, along with that of malondialdehyde in erythrocytes. Plasma concentrations of ceruloplasmin, TAC, albumin, total bilirubin, and uric acid were also determined. Clinical assessment was performed using a modified HHS scale and the WOMAC questionnaire. Intra-articular administration of a hyaluronic acid preparation significantly reduced pain in the knee and improved its functioning, regardless of the form of osteoarthritis. Not only clinical improvement was observed, but also beneficial changes in the blood antioxidant system. Comparable clinical improvement was observed in both forms of osteoarthritis of the knee. It was also beneficial changes in blood antioxidant system, especially in the group with secondary osteoarthritis.

  12. Characterization of hyaluronic acid interaction with calcium oxalate crystals: implication of crystals faces, pH and citrate.

    PubMed

    Lamontagne, Charles-Antoine; Plante, Gérard E; Grandbois, Michel

    2011-01-01

    Interaction between hyaluronic acid (HA) present at the surface of tubular epithelial cells and calcium oxalate monohydrate (COM) crystals is thought to play an important role in kidney stone formation. AFM-based force spectroscopy, where HA is covalently attached to AFM-probes, was used to quantify the interaction between HA and the surfaces of COM crystals. The work of adhesion of the HA-probe as well as the rupture force of single HA molecules were quantified in order to understand the molecular regulation of HA binding to COM crystals. Our results reveal that HA adsorbs to the crystal surface in physiological conditions. We also observed increased adhesion when the pH is lowered to a value that increases the risk of kidney stone formation. HA adhesion to the COM crystal surface can be suppressed by citrate, a physiological inhibitor of stone retention currently used in the treatment and prevention of kidney stone formation. Interestingly, we also observed preferential binding of HA onto the [100] face versus the [010] face, suggesting a major contribution of the [100] faces in the crystal retention process at the surface of tubular epithelial cells and the promotion of stone formation. Our results clearly establish a direct role for the glycosaminoglycan HA present at the surface of kidney tubular epithelium in the process of COM crystal retention. Copyright © 2011 John Wiley & Sons, Ltd.

  13. 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.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2013-08-01

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

  16. The effect of tenocyte/hyaluronic acid therapy on the early recovery of healing Achilles tendon in rats.

    PubMed

    Liang, Jen-I; Lin, Ping-Chia; Chen, Meng-Yi; Hsieh, Tsung-Hsun; Chen, Jia-Jin Jason; Yeh, Ming-Long

    2014-01-01

    The aim of this study was to explore the potential for a better recovery outcome for the Achilles tendon at an early healing stage when a mixed biomaterial-tenocyte injection is used. The experimental animals underwent single limb Achilles tendon transection followed by suturing repair. A solution of either hyaluronic acid with or without tenocytes or normal saline was randomly chosen to be injected around the injury site after surgery. To obtain the comprehensive recovery condition of the rats on different management protocols, the animals were evaluated histologically, mechanically, and functionally. A significant difference in the recovery condition was found in the injured tendon injected with the hyaluronic acid solution with tenocytes compared with the other groups. Tendon stiffness and the locomotion abilities of the rats with healing Achilles tendons were improved in the hyaluronic acid with tenocyte transplantation group. The acceleration of the inflammatory phase in rats with the hyaluronic acid with tenocyte injections might be the major reason for the better functional outcomes.

  17. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-06-01

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

  20. 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

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

    PubMed

    Fernández, Silvina; Córdoba, Mariana

    2017-04-01

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

  2. [Hyaluronic acid, receptor CD44, and their role in diabetic complications].

    PubMed

    Ievdokimova, N Iu

    2008-01-01

    Hyaluronic acid (HA) is a straight chain glycosaminoglycan polymer composed of repeating units of the disaccharide [-D-glucuronic acid-beta1,3-N-acetyl-D-glucosamine-beta1,4-]n, and is found in vertebrates and certain microorganisms. The molecular weight of HA chains is usually equal to approximately 1-10 and MDa, n > 10(3-4), although it can exists as oligosaccharides under some physiological and pathological conditions. HA resides on the cell surface or in the extracellular space, but it also occurred inside the mammalian cells. HA is synthesized in mammals by three enzymes with polymers of varying chain length. The biological functions of HA include the maintenance of elastoviscosity of liquid connective tissues, control of tissue hydration, supramolecular assembly of proteoglycans in the extracellular matrix and besides numerous receptor-mediated functions in cell attachment, mitosis, migration, tumor development, wound healing and inflammation. The extensive repertoire of biological functions of HA corresponds to the existence of a large repertoire of HA-binding proteins (hyaladherins). Many hyaladherins contain a common structural domain, termed a Link module, which is involved in ligand binding. The most important member of the Link module superfamily is the main HA receptor, CD44. CD44 has diverse functions including not only the organization and metabolism of extracellular matrix, but also engage the cytoskeleton and co-ordinate signaling events to enable the cell responce to changes in the environment. HA has an extraordinary high rate of turnover, and at the cellular level it is considered to be degraded progressively by a series of enzymatic reactions that generate polymers of decreasing sizes. HA biological effects are known to be determined by the polymer size and depend on the cell type. For example, the native high molecular weight HA is anti-angiogenic, while its degradation products (6-20 saccharides) stimulate endothelial cell proliferation

  3. Sequential robust design methodology and X-ray photoelectron spectroscopy to analyze the grafting of hyaluronic acid to glass substrates.

    PubMed

    Stile, Ranee A; Barber, Thomas A; Castner, David G; Healy, Kevin E

    2002-09-05

    Sequential Robust Design experiments and X-ray photoelectron spectroscopic (XPS) studies were performed to examine the immobilization of hyaluronic acid (HA) on glass substrates chemisorbed with N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS). Numerous reaction conditions were investigated, including the concentrations of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), N-hydroxysulfosuccinimide (Sulfo-NHS), and HA, and the reaction buffer type, concentration, and pH. The elemental surface compositions of carbon and silicon (C/Si ratio) were used to assess the extent of HA immobilization, leading to the identification of critical HA-binding reaction conditions and the determination of an optimum surface chemistry. The optimum chemistry consisted of 200 mM EDC, 50 mM Sulfo-NHS, 10 mM N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) (HEPES) buffer at a pH of 7.0, and 3 mg/mL HA. This work emphasizes the advantages of using Robust Design methods over traditional statistical experimental design, particularly when large numbers of variables are examined and costly analytical techniques are employed. Copyright 2002 Wiley Periodicals, Inc.

  4. 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

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

    PubMed

    Simone, Procopio; Alberto, Migliore

    2015-11-01

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

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

    PubMed

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

    2016-01-01

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

  7. Effect of ultrasonic degradation of hyaluronic acid extracted from rooster comb on antioxidant and antiglycation activities.

    PubMed

    Hafsa, Jawhar; Chaouch, Mohamed Aymen; Charfeddine, Bassem; Rihouey, Christophe; Limem, Khalifa; Le Cerf, Didier; Rouatbi, Sonia; Majdoub, Hatem

    2017-12-01

    Recently, low-molecular-weight hyaluronic acid (LMWHA) has been reported to have novel features, such as free radical scavenging activities, antioxidant activities and dietary supplements. In this study, hyaluronic acid (HA) was extracted from rooster comb and LMWHA was obtained by ultrasonic degradation in order to assess their antioxidant and antiglycation activities. Molecular weight (Mw) and the content of glucuronic acid (GlcA) were used as the index for comparison of the effect of ultrasonic treatment. The effects on the structure were determined by ultraviolet (UV) spectra and Fourier transform infrared spectra (FTIR). The antioxidant activity was determined by three analytical assays (DPPH, NO and TBARS), and the inhibitory effect against glycated-BSA was also assessed. The GlcA content of HA and LMWHA was estimated at about 48.6% and 47.3%, respectively. The results demonstrate that ultrasonic irradiation decreases the Mw (1090-181 kDa) and intrinsic viscosity (1550-473 mL/g), which indicate the cleavage of the glycosidic bonds. The FTIR and UV spectra did not significantly change before and after degradation. The IC50 value of HA and LWMHA was 1.43, 0.76 and 0.36 mg/mL and 1.20, 0.89 and 0.17 mg/mL toward DPPH, NO and TBARS, respectively. Likewise LMWHA exhibited significant inhibitory effects on the AGEs formation than HA. The results demonstrated that the ultrasonic irradiation did not damage and change the chemical structure of HA after degradation; furthermore, decreasing Mw and viscosity of LMWHA after degradation may enhance the antioxidant and antiglycation activity.

  8. Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity.

    PubMed

    Vilariño-Feltrer, G; Martínez-Ramos, C; Monleón-de-la-Fuente, A; Vallés-Lluch, A; Moratal, D; Barcia Albacar, J A; Monleón Pradas, M

    2016-01-01

    Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel's surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell-material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system. The paper entitled "Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity" reports on the development of a novel tubular scaffold and on how this scaffold acts on Schwann cells seeded in its interior as a template to produce macroscopic hollow continuous cylinders of tightly joined Schwann cells. This cellular structure is not found in nature and represents a truly engineered novel tissue, which obtains as a consequence of the specific cell-material interactions within the scaffold. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2012-05-01

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

  10. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action

    PubMed Central

    Moreland, Larry W

    2003-01-01

    Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA. PMID:12718745

  11. 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.

  12. Is intra-articular hyaluronic acid effective in treating osteoarthritis of the hip joint?

    PubMed

    Lieberman, Jay R; Engstrom, Stephen M; Solovyova, Olga; Au, Carol; Grady, James J

    2015-03-01

    Hyaluronic acid (HA) injections are used to treat osteoarthritis of the hip but their efficacy has not been clearly established. The purpose of this meta-analysis was to determine the effect of HA injections on hip pain. There were twenty-three studies that met our criteria and the mean decrease in visual analog scores (VAS) was -1.97 (95% CL, 2.83 to -1.12, P<0.0001). However, the clinical relevance of this change is difficult to determine since the decrease in VAS was only -0.27 in the six randomized trials in the study and the duration of follow-up in most studies was less than six months. Multicenter randomized trials are needed to determine the true efficacy of HA injections in decreasing pain associated with hip osteoarthritis. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. A novel oxido-viscosifying Hyaluronic Acid-antioxidant conjugate for osteoarthritis therapy: biocompatibility assessments.

    PubMed

    Kaderli, S; Boulocher, C; Pillet, E; Watrelot-Virieux, D; Roger, T; Viguier, E; Gurny, R; Scapozza, L; Möller, M

    2015-02-01

    To overcome the problem of fast degradation of Hyaluronic Acid (HA) in the treatment of osteoarthritis (OA), HA was protected against the oxidative stress generated by the pathology. Antioxidant conjugated HAs were synthesized and tested in vitro for their resistance in an oxidative environment mimicking OA. HA-4-aminoresorcinol (HA-4AR) displayed the interesting property of increasing in viscosity under oxidative conditions because of crosslinking induced by electron transfer. The novel HA polymer conjugate was shown to be biocompatible in vitro on fibroblast-like synoviocytes extracted from an arthritic patient. This HA conjugate was also assessed in vivo by intra-articular injection in healthy rabbits and was found to be comparable to the native polymer in terms of biocompatibility. This study suggests that HA-4AR is a promising candidate for a next generation viscosupplementation formulation. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2014-07-14

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

  15. 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

    2015-10-23

    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.

  16. Albumin and Hyaluronic Acid-Coated Superparamagnetic Iron Oxide Nanoparticles Loaded with Paclitaxel for Biomedical Applications.

    PubMed

    Vismara, Elena; Bongio, Chiara; Coletti, Alessia; Edelman, Ravit; Serafini, Andrea; Mauri, Michele; Simonutti, Roberto; Bertini, Sabrina; Urso, Elena; Assaraf, Yehuda G; Livney, Yoav D

    2017-06-22

    Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe₃O₄·DA-BSA/HA in water. Fe₃O₄·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX). The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe₃O₄·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system.

  17. Laparoscopic use of a hyaluronic acid carboxycellulose membrane slurry in gynecological oncology.

    PubMed

    Lipetskaia, Lioudmila; Silver, David F

    2010-01-01

    We evaluated the use of a hyaluronic acid-carboxycellulose membrane (HAC) slurry in complex laparoscopies. A gel-like mixture of HAC was prepared and applied in 171 consecutive complex laparoscopies on a gynecologic oncology service. The HAC slurry was used to coat deperitonealized surfaces and surgical pedicals to prevent postoperative adhesions. The technique is described and the outcomes are prospectively evaluated for feasibility and safety. There were no postoperative bowel obstructions, 1 pelvic hematoma in a patient on clopidogrel (Plavix) immediately prior to surgery, 8 postoperative ilea, and 1 bowel perforation. The bowel perforation occurred in a patient with extensive adhesiolysis and intraoperative bowel suturing. This report describes an easy approach to the laparoscopic application of HAC. Caution should be taken if HAC slurry is applied after significant bowel suturing because 1 of 9 patients with extensive adhesiolysis requiring suturing of the sigmoid colon developed sigmoid perforations.

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

    PubMed

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

    2016-06-01

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

  19. 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

  20. Sterilization of auto-crosslinked hyaluronic acid scaffolds structured in microparticles and sponges.

    PubMed

    Shimojo, Andréa Arruda Martins; de Souza Brissac, Isabela Cambraia; Pina, Lucas Martins; Lambert, Carlos Salles; Santana, Maria Helena Andrade

    2015-01-01

    This work evaluated the effects of UV irradiation, plasma radiation, steam and 70% ethanol treatments on the sterilization and integrity of auto-crosslinked hyaluronic acid (HA-ACP) scaffolds structured in microparticles and sponges aiming in vivo applications for regenerative medicine of bone tissue. The integrity of the microparticles was characterized by rheological behavior, while for the sponges, it was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. The effectiveness of the sterilization treatment was verified by the number of microorganism colonies in the samples after the treatments. In conclusion, plasma radiation was the best treatment for the sponges, while steam sterilization in the autoclave at 126°C (1.5 kgf/cm2) for 5 min was the best treatment for the microparticles.

  1. Ear Keloid Treated with Infiltrated Non-cross-linked Hyaluronic Acid and Cortisone Therapy.

    PubMed

    DI Stadio, Arianna

    Several treatments are available to treat the keloid scar. Keloids have the tendency to recur after surgical removal and new treatments for keloid scars include radiotherapy, cryotherapy or compressive therapy. Topical treatments have been also used to treat this pathology, such as injections or medical device applications. A 33-year-old man came to our attention and we treated him for a keloid scar located between the ear's helical tubercle and the ante-helix upper root of the left ear. This keloid arose 20 years earlier following a bilateral otoplasty. We proposed an association therapy using a non-cross-linked hyaluronic acid and cortisone. The associated treatment was able to determine a complete resolution of the keloid without recurrence several months later. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

    PubMed

    Li, Ranwei; Liu, Tiecheng; Wang, Ke

    2017-02-01

    Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.

  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. 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.

  5. [The first experience in using the stabilized hyaluronic acid preparation to correct lagophthalmos].

    PubMed

    Grusha, Ia O; Ismailova, D S; Ivanchenko, Iu F; Agafonova, E I

    2010-01-01

    The authors report the results of the first experience in using the stabilized hyaluronic acid preparation in patients with lagopthalmos in the presence of facial nerve palsy and thyroid eye disease and resultant keratopathy of varying degrees. The study included 21 patients, including 15 patients with facial nerve palsy and 6 with endocrine ophthalmopathy. The gel was injected externally to the levator aponeurosis and/or intramuscular, and/or under the pretarsal portion of the orbicularis oculi muscle, and/or subcutaneously. The use of this method led to a significant reduction of lagophthalmos and to a considerable corneal improvement. That of this procedure permitted avoidance of surgical intervention in some patients. The mean follow-up period after injection was 11.2 months (range 6-24 months).

  6. 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

  7. Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

    PubMed

    Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami

    2017-08-23

    Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Influence of hyaluronic acid on bacterial and fungal species, including clinically relevant opportunistic pathogens.

    PubMed

    Ardizzoni, Andrea; Neglia, Rachele G; Baschieri, Maria C; Cermelli, Claudio; Caratozzolo, Manuela; Righi, Elena; Palmieri, Beniamino; Blasi, Elisabetta

    2011-10-01

    Hyaluronic acid (HA) has several clinical applications (aesthetic surgery, dermatology, orthopaedics and ophtalmology). Following recent evidence, suggesting antimicrobial and antiviral properties for HA, we investigated its effects on 15 ATCC strains, representative of clinically relevant bacterial and fungal species. The in vitro system employed allowed to assess optical density of broth cultures as a measure of microbial load in a time-dependent manner. The results showed that different microbial species and, sometimes, different strains belonging to the same species, are differently affected by HA. In particular, staphylococci, enterococci, Streptococcus mutans, two Escherichia coli strains, Pseudomonas aeruginosa, Candida glabrata and C. parapsilosis displayed a HA dose-dependent growth inhibition; no HA effects were detected in E. coli ATCC 13768 and C. albicans; S. sanguinis was favoured by the highest HA dose. Therefore, the influence of HA on bacteria and fungi warrants further studies aimed at better establishing its relevance in clinical applications.

  9. 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

  10. 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.

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2011-01-01

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

  14. 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.

  15. Injection volumes of dextranomer/hyaluronic acid are increasing in the endoscopic management of vesicoureteral reflux.

    PubMed

    Sorensen, Mathew D; Koyle, Martin A; Cowan, Charles A; Zamilpa, Ismael; Shnorhavorian, Margarett; Lendvay, Thomas S

    2010-05-01

    Dextranomer/hyaluronic acid (Deflux) has been increasingly used for the treatment of vesicoureteral reflux (VUR). Experience has shown that injecting more volume of material is necessary to achieve greater success. We evaluate trends in the number of vials being used to treat VUR using a multi-institutional database and data from patients treated at our own institution. Children of age 0-19 years in the Pediatric Health Information System (PHIS) database from 2003 to 2008 were extracted with a VUR diagnosis (ICD-9 593.7x) and subureteric injection procedure code (CPT 52327). We identified children with reflux treated with endoscopic injection at Seattle Children's Hospital from 2005 to 2008. Hospital trends of the number of vials used were evaluated using multivariate linear regression. From 2003 to 2008, we identified 4,078 endoscopic injection procedures in PHIS. There was a 33% increase in the average number of vials used per patient (p < 0.0001) with more than a threefold increase in the number of patients receiving three or more vials per procedure. All institutions increased the average vials used per patient with the most pronounced increase at the highest-volume centers. These trends were also present in the 186 children treated at our own institution. Over the study period there was an increase in the number of vials of dextranomer/hyaluronic acid being used per patient to treat children with VUR. This practice may improve success rates but will increase the cost of treatment due to the inherent expense of the material.

  16. Extracellular component hyaluronic acid and its receptor Hmmr are required for epicardial EMT during heart regeneration.

    PubMed

    Missinato, Maria A; Tobita, Kimimasa; Romano, Nicla; Carroll, James A; Tsang, Michael

    2015-09-01

    After injury, the adult zebrafish can regenerate the heart. This requires the activation of the endocardium and epicardium as well as the proliferation of pre-existing cardiomyocytes to replace the lost tissue. However, the molecular mechanisms involved in this process are not completely resolved. In this work, we aim to identify the proteins involved in zebrafish heart regeneration and to explore their function. Using a proteomic approach, we identified Hyaluronan-mediated motility receptor (Hmmr), a hyaluronic acid (HA) receptor, to be expressed following ventricular resection in zebrafish. Moreover, enzymes that produce HA, hyaluronic acid synthases (has), were also expressed following injury, suggesting that this pathway may serve important functions in the regenerating heart. Indeed, suppression of HA production, as well as depletion of Hmmr, blocked cardiac regeneration. Mechanistically, HA and Hmmr are required for epicardial cell epithelial-mesenchymal transition (EMT) and their subsequent migration into the regenerating ventricle. Furthermore, chemical inhibition of Focal Adhesion Kinase (FAK) or inhibition of Src kinases, downstream effectors of Hmmr, also prevented epicardial cell migration, implicating a HA/Hmmr/FAK/Src pathway in this process. In a rat model of myocardial infarction, both HA and HMMR were up-regulated and localized in the infarct area within the first few days following damage, suggesting that this pathway may also play an important role in cardiac repair in mammals. HA and Hmmr are required for activated epicardial cell EMT and migration involving the FAK/Src pathway for proper heart regeneration. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

    Baldini, Alberto; Zaffe, Davide; Nicolini, Gabriella

    2010-01-01

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

  19. Hyaluronic Acid Versus Ultrasonic Resorbable Pin Fixation for Space Maintenance in Non-Grafted Sinus Lifting.

    PubMed

    Göçmen, Gökhan; Atalı, Onur; Aktop, Sertac; Sipahi, Ayşegül; Gönül, Onur

    2016-03-01

    An ultrasonic resorbable pin (SonicWeld, KLS Martin, Mühlheim, Germany) was compared with hyaluronic acid (Hyaloss Matrix, Anika Therapeutics, Bedford, MA) for their ability to maintain space in non-grafted sinus lifting. A comparative split-mouth study was designed and implemented. Six women and 4 men were included (mean age, 56.7 yr). The primary predictors hyaluronic acid (HA) application and ultrasonic resorbable pin fixation (URPF) were coded as binary variables. The primary outcome variables were height of alveolar bone (HAB) and reduction in sinus volume (RSV). Secondary outcomes were bone density and implant survival. The postoperative mean HAB was significantly higher than the preoperative mean HAB on the 2 sides (P < .05). Mean increases in HAB and RSV on the URPF side were significantly greater than those on the HA side (P < .05). In total, patients were treated with 40 implants. No type I bone quality was identified; 14 (35%) implants were inserted in type II bone, 22 (50%) in type III bone, and 6 (15%) in type IV bone. There was no statistically meaningful difference between the 2 sides for implant survival or bone quality. At 6 months, all implants were clinically stable and the definitive prostheses were functional, resulting in a survival rate of 100%. There was sufficient bone height to eventually place implants on the 2 sides in all patients. The 2 techniques yielded predictable outcomes in implant survival and bone quality. However, HAB and RSV were considerably greater on the URPF side. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2010-10-15

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

  3. Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

    PubMed Central

    Zhao, Meng-Dan; Cheng, Jin-Lin; Yan, Jing-Jing; Chen, Feng-Ying; Sheng, Jian-Zhong; Sun, Dong-Li; Chen, Jian; Miao, Jing; Zhang, Run-Ju; Zheng, Cai-Hong; Huang, He-Feng

    2016-01-01

    To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis. PMID:27099493

  4. Magnetic hyaluronic acid nanospheres via aqueous Diels-Alder chemistry to deliver dexamethasone for adipose tissue engineering.

    PubMed

    Jia, Yang; Fan, Ming; Chen, Huinan; Miao, Yuting; Xing, Lian; Jiang, Bohong; Cheng, Qifan; Liu, Dongwei; Bao, Weikang; Qian, Bin; Wang, Jionglu; Xing, Xiaodong; Tan, Huaping; Ling, Zhonghua; Chen, Yong

    2015-11-15

    Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels-Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels-Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications.

  5. Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells.

    PubMed

    Tran, Tuan Hiep; Choi, Ju Yeon; Ramasamy, Thiruganesh; Truong, Duy Hieu; Nguyen, Chien Ngoc; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2014-12-19

    Hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) were developed for tumor-targeted delivery of vorinostat (VRS), a histone deacetylase inhibitor. HA, a naturally occurring polysaccharide, which specifically binds to the CD44 receptor, was coated on a cationic lipid core through electrostatic interaction. After the optimization process, HA-coated VRS-loaded SLNs (HA-VRS-SLNs) were spherical, core-shell nanoparticles, with small size (∼100 nm), negative charge (∼-9 mV), and narrow size distribution. In vitro release profile of HA-VRS-SLNs showed a typical bi-phasic pattern. In addition, the intracellular uptake of HA-VRS-SLNs was significantly enhanced in CD44 overexpressing cells, A549 and SCC-7 cells, but reduced when HA-VRS-SLNs were incubated with SCC-7 cells pretreated with HA or MCF-7 cells with low over-expressed CD44. Of particular importance, HA-VRS-SLNs were more cytotoxic than the free drug and VRS-SLNs in A549 and SCC-7 cells. In addition, HA shell provided longer blood circulation and reduced VRS clearance rate in rats, resulting in enhanced higher plasma concentration and bioavailability. These results clearly indicated the potential of the HA-functionalized lipid nanoparticle as a nano-sized drug formulation for chemotherapy.

  6. Spermatozoa bound to solid state hyaluronic acid show chromatin structure with high DNA chain integrity: an acridine orange fluorescence study.

    PubMed

    Yagci, Artay; Murk, William; Stronk, Jill; Huszar, Gabor

    2010-01-01

    During human spermiogenesis, the elongated spermatids undergo a plasma membrane remodeling step that facilitates formation of the zona pellucida and hyaluronic acid (HA) binding sites. Various biochemical sperm markers indicated that human sperm bound to HA exhibit attributes similar to that of zona pellucida-bound sperm, including minimal DNA fragmentation, normal shape, and low frequency of chromosomal aneuploidies. In this work, we tested the hypothesis that HA-bound sperm would be enhanced in sperm of high DNA chain integrity and green acridine orange fluorescence (AOF) compared with the original sperm in semen. Sperm DNA integrity in semen and in their respective HA-bound sperm fractions was studied in 50 men tested for fertility. In the semen samples, the proportions of sperm with green AOF (high DNA integrity) and red AOF (DNA breaks) were 54.9% ± 2.0% and 45.0% ± 1.9%, whereas in the HA-bound sperm fraction, the respective proportions were 99% and 1.0%, respectively. The data indeed demonstrated that HA shows a high degree of selectivity for sperm with high DNA integrity. These findings are important from the points of view of human sperm DNA integrity, sperm function, and the potential efficacy of HA-mediated sperm selection for intracytoplasmic sperm injection.

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

    PubMed

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

    2016-11-22

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

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

    PubMed Central

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

    2016-01-01

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

  9. Americium binding to humic acid.

    PubMed

    Peters, A J; Hamilton-Taylor, J; Tipping, E

    2001-09-01

    The binding of americium (Am) by peat humic acid (PHA) has been investigated at Am concentrations between 10(-1) and 10(-7) M at pH approximately 2.6 in the presence and absence of Cu as a competing ion. Cu-PHA binding was also investigated in order to derive independent binding constants for use in modeling the competitive binding studies. Humic ion-binding model VI was used to compare the acquired data with previously published binding data and to investigate the importance of high-affinity binding sites in metal-PHA binding. Am was not observed to bind to high-affinity, low-concentration binding sites. The model VI parameter deltaLK2 takes into accountthe small number of strong sites in PHA and was found to be important for Cu-PHA binding but not for Am-PHA binding, regardless of whether Cu was present. Analysis of the PHA sample revealed that it contained a considerable quantity of Fe not removed by the extraction procedure, much of which is believed to be present as Fe(III). Model VI was then used to investigate the possible importance of the presence of Fe(III) in the Am-PHA binding experiments. When Fe(III) was assumed to be present, improved descriptions of the data by model VI were obtained by assuming that all of the metals [Am, Cu, and Fe(III)] undergo strong binding. This highlights the importance of Fe(III) competition in metal-PHA binding studies and possible shortcomings in the extraction procedure used to extract PHA.

  10. "Physiologic ICSI": hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality.

    PubMed

    Parmegiani, Lodovico; Cognigni, Graciela Estela; Bernardi, Silvia; Troilo, Enzo; Ciampaglia, Walter; Filicori, Marco

    2010-02-01

    To evaluate the role of hyaluronic acid (HA) for sperm selection before intracytoplasmic sperm injection (ICSI). Three prospective studies. Private assisted reproduction center in Italy. Study 1: 20 men. Study 2: 15 men. Study 3: 206 couples treated with ICSI on a limited number of oocytes per patient (1-3) in accordance with Italian IVF law. Study 1: determination of sperm DNA fragmentation of HA-bound spermatozoa versus spermatozoa in polyvinylpyrrolidone (PVP). Study 2: assessment of nuclear morphology of HA-bound spermatozoa versus spermatozoa in PVP. Study 3: randomized study comparing conventional PVP-ICSI to ICSI in which the spermatozoa are selected for their capacity to bind to HA (HA-ICSI). Study 1: sperm DNA fragmentation rate. Study 2: sperm nucleus normalcy rate according to motile sperm organellar morphology examination criteria. Study 3: fertilization, embryo quality and development, and implantation and pregnancy. Spematozoa bound to HA show a significant reduction in DNA fragmentation (study 1) and a significant improvement in nucleus normalcy (study 2) compared with spermatozoa immersed in PVP. Furthermore, injection of HA-bound spermatozoa (HA-ICSI) significantly improves embryo quality and development (study 3). Hyaluronic acid may optimize ICSI outcome by favoring selection of spermatozoa without DNA fragmentation and with normal nucleus. Furthermore, HA may also be used to speed up the selection of spermatozoa with normal nucleus during intracytoplasmic morphologically selected sperm injection (IMSI). Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Hempfling, Harald

    2007-05-01

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

  12. 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

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

    PubMed

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

    2011-01-01

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

  14. 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

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

    PubMed

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

    2013-09-01

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

  16. Intra-articular treatment of knee osteoarthritis. A comparative study between hyaluronic acid and 6-methyl prednisolone acetate.

    PubMed

    Leardini, G; Mattara, L; Franceschini, M; Perbellini, A

    1991-01-01

    The efficacy and tolerability of 20 mg of hyaluronic acid were compared in an open, randomized trial with that of 40 mg of 6-methylprednisolone acetate, administering them both by an intra-articular route once a week for 3 weeks to patients suffering from inflammatory knee osteoarthritis. The results of the study showed that for up to one week after the end of treatment hyaluronic acid's analgesic activity was comparable to that of the steroid, while at the end of the follow-up (45 days after the end of treatment) all the pain monitoring parameters presented significant differences in favour of the HA-treated group. Both treatments were well tolerated, since no local or systemic adverse reactions were observed.

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

    PubMed

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

    2014-03-17

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

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

    PubMed

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

    2016-01-01

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

  19. 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.

  20. Increased cartilage volume after injection of hyaluronic acid in osteoarthritis knee patients who underwent high tibial osteotomy.

    PubMed

    Chareancholvanich, Keerati; Pornrattanamaneewong, Chaturong; Narkbunnam, Rapeepat

    2014-06-01

    High tibial osteotomy (HTO) is a surgical procedure used to correct abnormal mechanical loading of the knee joint; additionally, intra-articular hyaluronic acid injections have been shown to restore the viscoelastic properties of synovial fluid and balance abnormal biochemical processes. It was hypothesized that combining HTO with intra-articular hyaluronic acid injections would have benefit to improve the cartilage volume of knee joints. Forty patients with medial compartment knee osteoarthritis (OA) were randomly placed into 1 of 2 groups. The study group (n = 20) received 2 cycles (at 6-month intervals) of 5 weekly intra-articular hyaluronic acid injections after HTO operation. The control group (n = 20) did not receive any intra-articular injections after HTO surgery. Cartilage volume (primary outcome) was assessed by magnetic resonance imaging (MRI) pre-operatively and 1 year post-operatively. Treatment efficacy (secondary outcomes) was evaluated with the Western Ontario and McMaster Universities OA Index (WOMAC) and by the comparison of the total rescue medication (paracetamol/diclofenac) used (weeks 6, 12, 24, 48). MRI studies showed a significant increase in total cartilage volume (p = 0.033), lateral femoral cartilage volume (p = 0.044) and lateral tibial cartilage volume (p = 0.027) in the study group. Cartilage volume loss was detected at the lateral tibial plateau in the control group. There were significant improvements after surgery in both groups for all subscales of WOMAC scores (p < 0.001) compared to the baseline. However, no difference was found between the two groups. The study group had significantly lower amounts of diclofenac consumption (p = 0.017). Based on the findings of the present study, intra-articular hyaluronic acid injections may be beneficial for increasing total cartilage volume and preventing the loss of lateral tibiofemoral joint cartilage after HTO. Therapeutic study, Level I.

  1. Kinematic and kinetic modifications in walking pattern of hip osteoarthritis patients induced by intra-articular injections of hyaluronic acid.

    PubMed

    Paoloni, Marco; Di Sante, Luca; Dimaggio, Mauro; Bernetti, Andrea; Mangone, Massimiliano; Di Renzo, Sara; Santilli, Valter

    2012-08-01

    A growing body of evidence points to the efficacy of intra-articular injections of hyaluronic acid, in dealing with pain and function in hip osteoarthritis. To date, however, no data exist as to this treatment's effect on walking pattern. We performed a prospective, open study in order to verify, in a group of 20 hip osteoarthritis patients (12 men, 8 women, mean age 60.5, range 47-73), the clinical effects of 3 intra-articular injections of 2 ml of hyaluronic acid in the hip (1/week) in terms of pain and function at 1 (T1), 3 (T2) and 6-month (T3) follow-ups, as well as changes in the kinematics and kinetics of gait at 6-month follow-up. Pain as measured with visual analog scale significantly dropped after this procedure (P<0.0001). A significant improvement was noted regarding stiffness (P=0.005) and disability (P=0.04), as measured by the Western Ontario and McMaster Universities osteoarthritis index. As regards gait analysis, patients at T3 walked with higher cadence (P=0.004) and stride length (P=0.02) compared to T0. Moreover, a significant increase for the pelvic tilt at heel contact (P=0.0004) and for hip flexion-extension moment at loading response sub-phases of gait cycle (P=0.02) was noted at T3. In line with current literature, our patients display clinical improvement 6 months after intra-articular injections of hyaluronic acid, accompanied by changes in walking pattern, as measured by instrumental gait analysis. The kinematic and kinetic changes observed may be the consequence of the therapeutic effect of intra-articular injections of hyaluronic acid. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Desire for Penile Girth Enhancement and the Effects of the Self-Injection of Hyaluronic Acid Gel

    PubMed Central

    Coskuner, Enis Rauf; Canter, Halil Ibrahim

    2012-01-01

    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

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2017-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. 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.

  9. 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

  10. Efficacy of hyaluronic acid spray on swelling, pain, and trismus after surgical extraction of impacted mandibular third molars.

    PubMed

    Koray, M; Ofluoglu, D; Onal, E A; Ozgul, M; Ersev, H; Yaltirik, M; Tanyeri, H

    2014-11-01

    The aim of this study was compare the efficacies of two oral sprays in reducing swelling, pain, and trismus after the extraction of impacted mandibular third molars. This prospective double-blind, randomized, crossover clinical trial included 34 patients with bilateral symmetrically impacted mandibular third molars of similar surgical difficulty. Hyaluronic acid or benzydamine hydrochloride spray was applied (two pumps) to the extraction area, three times daily for 7 days. Swelling was evaluated using a tape measure method, pain with a visual analogue scale (VAS), and trismus by measuring the maximum inter-incisal opening. Assessments were made on the day of surgery and on days 2 and 7 after surgery. Statistically significant differences were detected for the swelling and trismus values between the two treatment groups on the second postoperative day (P=0.002 and P=0.03, respectively). However, there was no statistically significant difference in VAS scores between the two groups. The administration of hyaluronic acid spray was more effective than benzydamine hydrochloride spray in reducing swelling and trismus. Although no evidence of a reduction in pain levels was detected, hyaluronic acid appears to offer a beneficial effect in the management of swelling and trismus during the immediate postoperative period following impacted third molar surgery. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. Human growth factor cream and hyaluronic Acid serum in conjunction with micro laser peel: an efficient regimen for skin rejuvenation.

    PubMed

    Gold, Michael H; Katz, Bruce E; Cohen, Joel L; Biron, Julie

    2010-12-01

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

  12. 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.

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

    PubMed

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

    2012-11-01

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

  14. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  16. 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.

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

    PubMed

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

    2003-08-01

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

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

    PubMed

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

    2014-06-25

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

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

    PubMed

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

    2015-03-20

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

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

    PubMed

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

    2013-10-01

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

  1. 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.

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

    PubMed

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

    2016-09-01

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

  3. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-28

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

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

    PubMed

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

    2016-07-25

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

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

    PubMed

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

    2007-01-01

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

  8. Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid.

    PubMed

    Silva, C C; Domingues, A L; Lopes, E P; Morais, C N; Santos, R B; Luna, C F; Nader, H B; Martins, J R

    2011-04-01

    Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 μg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

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

    PubMed

    Curran, Monique P

    2010-11-01

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

  10. The design of antimicrobial LL37-modified collagen-hyaluronic acid detachable multilayers.

    PubMed

    Cassin, Margaret E; Ford, Andrew J; Orbach, Sophia M; Saverot, Scott E; Rajagopalan, Padmavathy

    2016-08-01

    The design of antimicrobial membranes and thin films are critical for the design of biomaterials that can combat bacterial contamination. Since the long-term use of conventional antibiotics can result in bacterial resistance, there is a critical need to incorporate natural antimicrobial peptides (AMPs) that not only prevent a wide range of pathogens from causing infections but can also promote many beneficial outcomes in wounded tissues. We report the design and antimicrobial properties of detachable collagen (COL)/hyaluronic acid (HA) polyelectrolyte multilayers (PEMs) modified with LL-37, a naturally occurring human AMP. LL-37 was physically adsorbed and chemically immobilized on the surface of PEMs. The antimicrobial and cytotoxic properties of PEMs were tested with Gram-negative Escherichia coli (E. coli, strain DH10B) and primary rat hepatocytes, respectively. The ability to prevent bacterial adhesion and to neutralize an E. coli layer was investigated as a function of LL-37 concentration. An interesting trend was that even unmodified PEMs exhibited a 40% reduction in bacterial adhesion. When LL-37 was physically adsorbed on PEMs, bacterial adhesion was significantly lower on the surface of the films as well as in the surrounding broth. Immobilizing LL-37 resulted in less than 3% bacterial adhesion on the surface due to the presence of the peptide. LL-37 modified PEMs did not result in any cytotoxicity up to input concentrations of 16μM. More importantly, urea and albumin secretion by hepatocytes were unaffected even at high LL-37 concentrations. The COL/HA PEMs can serve as antimicrobial coatings, biological membranes and as in vitro platforms to investigate pathogen-tissue interactions. Antimicrobial peptides (AMPs) are emerging as an alternative to conventional antibiotics. We report the antimicrobial properties of detachable collagen (COL)/hyaluronic acid (HA) polyelectrolyte multilayers (PEMs) modified with LL-37, a human AMP. The antimicrobial and

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

    PubMed Central

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

    2015-01-01

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

  12. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis

    PubMed Central

    Arrich, Jasmin; Piribauer, Franz; Mad, Philipp; Schmid, Daniela; Klaushofer, Klaus; Müllner, Marcus

    2005-01-01

    Background Osteoarthritis of the knee affects up to 10% of the elderly population. The condition is frequently treated by intra-articular injection of hyaluronic acid. We performed a systematic review and meta-analysis of randomized controlled trials to assess the effectiveness of this treatment. Methods We searched MEDLINE, EMBASE, CINAHL, BIOSIS and the Cochrane Controlled Trial Register from inception until April 2004 using a combination of search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. We extracted data on pain at rest, pain during or immediately after movement, joint function and adverse events. Results Twenty-two trials that reported usable quantitative information on any of the predefined end points were identified and included in the systematic review. Even though pain at rest may be improved by hyaluronic acid, the data available from these studies did not allow an appropriate assessment of this end point. Patients who received the intervention experienced a reduction in pain during movement: the mean difference on a 100-mm visual analogue scale was –3.8 mm (95% confidence interval [CI] –9.1 to 1.4 mm) after 2–6 weeks, –4.3 mm (95% CI –7.6 to –0.9 mm) after 10–14 weeks and –7.1 mm (95% CI –11.8 to –2.4 mm) after 22–30 weeks. However, this effect was not compatible with a clinically meaningful difference (expected to be about 15 mm on the visual analogue scale). Furthermore, the effect was exaggerated by trials not reporting an intention-to-treat analysis. No improvement in knee function was observed at any time point. Even so, the effect of hyaluronic acid on knee function was more favourable when allocation was not concealed. Adverse events occurred slightly more often among patients who received the intervention (relative risk 1.08, 95% CI 1.01 to 1.15). Only 4 trials explicitly reported allocation concealment, had blinded outcome assessment and presented intention

  13. A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

    PubMed

    Oz, Murat; Cetinkaya, Nilufer; Bas, Sevda; Korkmaz, Elmas; Ozgu, Emre; Terzioglu, Gokay Serdar; Buyukkagnici, Umran; Akbay, Serap; Caydere, Muzaffer; Gungor, Tayfun

    2016-09-01

    Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/μL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1β) expressions were evaluated. The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1β expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Sohrabi, Mehri; Hesaraki, Saeed; Kazemzadeh, Asghar

    2014-04-01

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

  16. Topical Hyaluronic acid vs. Standard of Care for the Prevention of Radiation Dermatitis after Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

    PubMed Central

    Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

    2014-01-01

    Purpose To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥ grade 2 radiation dermatitis after adjuvant breast radiation (RT) compared with best supportive care. Materials and Methods Women with breast cancer who had undergone lumpectomy and were to receive whole-breast RT to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel, on the medial half or the lateral half of the irradiated breast, and the control gel to the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥grade 2 dermatitis. Results The study closed early based on a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed significantly higher rate of ≥grade 2 dermatitis than did skin treated with petrolatum gel (61.5% [40/65] vs. 47.7% [31/65], P = 0.027). Only one patient developed grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than petrolatum gel at the end of RT (42% vs. 14%, P = 0.003). Conclusion We found no benefit from use of a topical hyaluronic acid-based gel for reducing the development of grade ≥2 dermatitis after adjuvant RT for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop. PMID:22172912

  17. Single intra-articular injection of high molecular weight hyaluronic acid for hip osteoarthritis.

    PubMed

    Rivera, Fabrizio

    2016-03-01

    Intra-articular (IA) injection of hyaluronic acid (HA) into the hip joint appears to be safe and well tolerated but only a small number of randomized clinical trials in humans has been published. The objective of this prospective study was to evaluate the efficacy and safety of a single IA injection of high-molecular-weight (2800 kDa) HA (Coxarthrum) for hip osteoarthritis. All patients received a single IA administration of 2.5 % sodium hyaluronate (75 mg/3 mL) of high molecular weight. Fluoroscopy requires an iodized contrast medium (iopamidol, 1 ml) which highlights the capsule before administering HA. Patients were evaluated before IA injection (T0), after 3 months, after 6 months and after 1 year from injection. Results were evaluated by the Brief Pain Inventory (BPI II), Harris Hip Score and a visual analog scale of pain (pain VAS). All treated patients were considered for statistical analysis. Two hundred seven patients were included at T0. The mean age was 67 years (range 46-81). Regarding BPI severity score, changes in pain between T0 and the three following visits were statistically highly significant (p < 0.001). Changes in pain score compared to the previous visit were statistically significant for the worst pain in the second quarter post-intervention (p = 0.037) and for mean pain in the second semester post-intervention (p = 0.043) The evolution of the Harris Hip Score was statistically highly significant (p < 0.001) between T0 and the following visits (T0 + 3 months, T0 + 6 months and T0 + 12 months); after a significant change between T0 and T0 + 3 months, the score remained stable. The evolution of the pain VAS showed a statistically highly significant improvement (p < 0.001) between T0 and T0 + 3 months; thereafter it remained stable from the first quarter post-intervention. No serious adverse event was noted; 12 cases (0.5 %) of pain associated with transient synovitis are noteworthy. This study shows that a single IA injection of Coxarthrum is

  18. Pervaporation dehydration of ethanol by hyaluronic acid/sodium alginate two-active-layer composite membranes.

    PubMed

    Gao, Chengyun; Zhang, Minhua; Ding, Jianwu; Pan, Fusheng; Jiang, Zhongyi; Li, Yifan; Zhao, Jing

    2014-01-01

    The composite membranes with two-active-layer (a capping layer and an inner layer) were prepared by sequential spin-coatings of hyaluronic acid (HA) and sodium alginate (NaAlg) on the polyacrylonitrile (PAN) support layer. The SEM showed a mutilayer structure and a distinct interface between the HA layer and the NaAlg layer. The coating sequence of two-active-layer had an obvious influence on the pervaporation dehydration performance of membranes. When the operation temperature was 80 °C and water concentration in feed was 10 wt.%, the permeate fluxes of HA/Alg/PAN membrane and Alg/HA/PAN membrane were similar, whereas the separation factor were 1130 and 527, respectively. It was found that the capping layer with higher hydrophilicity and water retention capacity, and the inner layer with higher permselectivity could increase the separation performance of the composite membranes. Meanwhile, effects of operation temperature and water concentration in feed on pervaporation performance as well as membrane properties were studied.

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

    PubMed Central

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

    2016-01-01

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

  20. Effectiveness of hyaluronic acid and its derivatives on chronic wounds: a systematic review.

    PubMed

    Shaharudin, A; Aziz, Z

    2016-10-02

    Hyaluronic acid (HA) and its derivatives are used for chronic wounds, but evidence of their effectiveness remains unclear. The aim of this study was to provide more updated evidence for the effectiveness of HA (or its derivatives) compared with placebo or other agents for promoting healing in chronic wounds. The Cochrane Central Register of Controlled Trials, MEDLINE via Ovid Online, CINAHL and the EMBASE via EBSCO host databases were searched. Drug companies and experts in wounds were also contacted. Randomised controlled trials of HA (or its derivatives) compared with control were eligible for inclusion. We identified nine randomised controlled trials involving 865 participants with chronic wounds were included in the review. The reporting for mixed arterial and venous ulcers seems to be better quality than that for venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). Studies provided little evidence regarding the claimed effects of HA or its derivaties on healing of chronic wounds. However, there is some evidence on their effectiveness for reducing pain intensity for mixed arterial and venous ulcers, which involved 255 patients (MD=-6.78 [95% CI: -11.10 to -2.46]). Evidence to guide decisions regarding the use of HA or its derivatives to promote wound healing is still limited. More good-quality randomised controlled trials are warranted.

  1. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid.

    PubMed

    Spaková, Tímea; Rosocha, Ján; Lacko, Marek; Harvanová, Denisa; Gharaibeh, Ahmed

    2012-05-01

    This study aimed to find a simple, cost-effective, and time-efficient method for the preparation of platelet-rich plasma (PRP), so the acquired benefits will be readily available for multiple procedures in smaller outpatient clinics and to explore the safety and efficacy of the application of PRP in the treatment of degenerative lesions of articular cartilage of the knee. The study was designed as a prospective, cohort study with a control group. A total of 120 patients with Grade 1, 2, or 3 osteoarthritis according to the Kellgren and Lawrence grading scale were enrolled in the study. One group of patients was treated using three intra-articular applications of PRP, and the second group of patients was given three injections of hyaluronic acid. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index and the 11-point pain intensity Numeric Rating Scale. On average, a 4.5-fold increase in platelet concentration was obtained in the PRP group. No severe adverse events were observed. Statistically significantly better results in the Western Ontario and McMaster Universities Osteoarthritis Index and Numeric Rating Scale scores were recorded in a group of patients who received PRP injections after a 3- and 6-mo follow-up. Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis. Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed.

  2. The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain

    PubMed Central

    Anand, A

    2013-01-01

    Introduction Knee osteoarthritis (OA) is a common and progressive joint disease. Treatment options for knee OA vary from simple analgesia in mild cases to knee replacement for advanced disease. Knee pain due to moderate OA can be targeted with intra-articular injections. Steroid injections have been used widely in managing acute flare-ups of the disease. In recent years, viscosupplementation has been used as a therapeutic modality for the management of knee OA. The principle of viscosupplementation is based on the physiological properties of the hyaluronic acid (HA) in the synovial joint. Despite a sound principle and promising in vitro studies, clinical studies have been less conclusive on the effectiveness of HA in managing osteoarthritic knee pain. The aim of this systematic review was to assess the effectiveness of HA intra-articular injections in the management of osteoarthritic knee pain. Methods A systematic review of the literature was performed using MEDLINE®, Embase™ and CINAHL® (Cumulative Index to Nursing and Allied Health Literature). The databases were searched for randomised controlled trials available on the effectiveness of HA intra-articular injections in managing osteoarthritic knee pain. Results The search yielded 188 studies. Of these, 14 met the eligibility criteria and were reviewed in chronological order. Conclusions HA intra-articular injections have a modest effect on early to moderate knee OA. The effect peaks at around 6–8 weeks following administration, with a doubtful effect at 6 months. PMID:24165334

  3. Efficacy and safety of intraarticular hyaluronic acid in the treatment of hip osteoarthritis: a systematic review.

    PubMed

    Fernández López, J C; Ruano-Ravina, A

    2006-12-01

    This study sought to use a systematic review to ascertain the efficacy and safety of hyaluronic acid (HA) in the treatment of hip osteoarthritis (OA). A protocolized search was made of a number of electronic databases, including Medline, EMBASE, Cochrane Library and Health Technology Assessment (HTA) among others. Two independent reviewers applied a series of inclusion and exclusion criteria to the studies located in the search, and selected only those that included more than 20 patients; had a follow-up period of more than 1 week; and exclusively assessed the efficacy and/or effectiveness of HA in patients with confirmed hip OA. A total of eight studies, comprising clinical trials and one review, met the inclusion criteria, and had study populations ranging from 22 to 104 patients. Only two of the trials were controlled: one compared two HAs of different molecular weights; and the other compared HA with corticoids and a placebo. Relief of pain was estimated to be around 40-50% by most studies, though the duration of this post-treatment effect was not known. Based on available evidence, HA treatment should only be used under careful supervision by the clinician and just in those cases where other treatments have failed in hip OA. There are methodologic limitations displayed in the literature, which were mainly the absence of a control group in most of the studies, overly short follow-up periods, and different ways of measuring outcomes.

  4. Intra-articular hyaluronic acid vs platelet-rich plasma in the treatment of hip osteoarthritis.

    PubMed

    Di Sante, Luca; Villani, Ciro; Santilli, Valter; Valeo, Massimo; Bologna, Emmalisa; Imparato, Luca; Paoloni, Marco; Iagnocco, Annamaria

    2016-12-05

    To compare the efficacy of ultrasound-guided intra-articular (IA) treatment with platelet-rich plasma (PRP) versus viscosupplementation (hyaluronic acid HA) in hip osteoarthritis. METHODS: A total of 43 patients affected by monolateral severe hip osteoarthritis (OA) were included in the study. Patients were randomized to receive either intra-articular PRP (3 ml) or HA (30 mg/2 ml; 1,000-2,900 kDa), 3 injections in total - 1/week. Clinical assessments for each patient were made at baseline (T0), 4 (T1), and 16 weeks (T2) of follow-up. The primary efficacy outcome was pain reduction as measured by VAS and by WOMAC pain subscale. Data analysis revealed that, compared to T0, in the PRP-treated group VAS scores significantly decreased at T1 but not at T2, thereby indicating an early effect on pain which was not maintained at a longer term follow-up. In the HA group a significant decrease of both VAS and WOMAC values was registered only between T0 and T2. Intra-articular PRP had an immediate effect on pain that was not maintained at longer term follow-up when, on the contrary, the effects of intra-articular HA were evident.

  5. Rapid analgesic onset of intra-articular hyaluronic acid with ketorolac in osteoarthritis of the knee.

    PubMed

    Lee, Sang Chul; Rha, Dong-Wook; Chang, Won Hyuk

    2011-01-01

    The purpose of this study was to evaluate the efficacy of intra-articular ketorolac to improve intra-articular hyaluronic acid (HA) therapy in knee osteoarthritis with respect to the initiation of pain relief. This study was designed as a single-blind study with a blinded observer and a 3-month follow-up. Forty-three patients with knee osteoarthritis were randomized to the ketorolac group (n=21) or the HA group (n=22). Ketorolac group members were given three weekly intra-articular injections of HA with ketorolac and then two weekly intra-articular injections of HA; and HA group members were given five weekly intra-articular HA injections. Visual analog scale (VAS), pain rating score (PRS) and adverse events were assessed at baseline and at 1st, 3rd, 5th, and 16th week after treatment commencement. Significant improvement regarding pain assessment tools was observed in the ketorolac group by the addition of ketorolac to HA as compared with the HA group within 16 weeks of follow-up (p < 0.05). In the ketorolac group, 5 of the 21 subjects developed focal post-injection knee pain for about 8 hours after injection. Intra-articular HA with ketorolac showed more rapid analgesic onset than intra-articular HA alone and did not induce any serious complications.

  6. The effectiveness of hyaluronic acid intra-articular injections in managing osteoarthritic knee pain.

    PubMed

    Trigkilidas, D; Anand, A

    2013-11-01

    Knee osteoarthritis (OA) is a common and progressive joint disease. Treatment options for knee OA vary from simple analgesia in mild cases to knee replacement for advanced disease. Knee pain due to moderate OA can be targeted with intra-articular injections. Steroid injections have been used widely in managing acute flare-ups of the disease. In recent years, viscosupplementation has been used as a therapeutic modality for the management of knee OA. The principle of viscosupplementation is based on the physiological properties of the hyaluronic acid (HA) in the synovial joint. Despite a sound principle and promising in vitro studies, clinical studies have been less conclusive on the effectiveness of HA in managing osteoarthritic knee pain. The aim of this systematic review was to assess the effectiveness of HA intra-articular injections in the management of osteoarthritic knee pain. A systematic review of the literature was performed using MEDLINE®, Embase™ and CINAHL® (Cumulative Index to Nursing and Allied Health Literature). The databases were searched for randomised controlled trials available on the effectiveness of HA intra-articular injections in managing osteoarthritic knee pain. The search yielded 188 studies. Of these, 14 met the eligibility criteria and were reviewed in chronological order. HA intra-articular injections have a modest effect on early to moderate knee OA. The effect peaks at around 6-8 weeks following administration, with a doubtful effect at 6 months.

  7. Esthetic Reconstruction of Diastema with Adhesive Tooth-Colored Restorations and Hyaluronic Acid Fillers

    PubMed Central

    2017-01-01

    Objective. This report presents a comprehensive esthetic treatment with adhesive tooth-colored restorations in a combination with hyaluronic acid (HA) fillers of diastema in an orthodontic patient with relapse. Case Report. A 36-year-old female patient consulted about 1.5–2 mm midline diastema after an orthodontic relapse of replacing missing central incisors with lateral incisors and dark-colored gingival tissue as a result of a metal post and core with porcelain fused to a metal (PFM) crown at the left lateral incisor. Restorative treatments included replacing the PFM with all-ceramic material and placing a ceramic veneer on the right lateral incisor. To close the space, crown forms of both lateral incisors were altered. A direct resin composite was then used to reform right and left canines to a more ideal lateral incisor shape. An HA fillers injection was used to fill the remaining open gingival embrasure. Eighteen months after treatment, the interdental papilla remained stable and the patient was satisfied with the result. Conclusion. Esthetic reconstruction of diastema and open gingival embrasure in this case can be accomplished without orthodontic retreatment. Tooth-colored restorations and HA filler injection appear as a promising modality to address this patient's esthetic concern. PMID:28386488

  8. Polyethyleneimine modified poly(Hyaluronic acid) particles with controllable antimicrobial and anticancer effects.

    PubMed

    Sahiner, Nurettin; Sagbas, Selin; Sahiner, Mehtap; Ayyala, Ramesh S

    2017-03-01

    Poly(hyaluronic acid) (p(HA)) particles with sizes from few hundred nm to few tens of micrometer were synthesized by using epoxy groups containing crosslinker glycerol diglycidyl ether (GDE) with high yield, 94±5%. P(HA) particles were oxidized by treatment with sodium periodate and then reacted with cationic polyethyleneimine (PEI) at 1:0.5, 1:1, and 1:2 wt ratio of p(HA):PEI to obtain p(HA)-PEI particles. From zeta potential measurements, isoelectronic points of bare p(HA) particles increased to pH 8.7 from 2.7 after modification with cationic PEI. New properties, such as antibacterial property, were attained for p(HA)-PEI after modification. The highest minimum bactericidal concentration (MBC) values were 0.5, 1, and 0.5mg/mL against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis species for 1:0.5 ratio of p(HA)-PEI at 72h incubation time. Moreover, the p(HA)-PEI particles were found to be biocompatible with L929 fibroblast cells, and interestingly, p(HA)-PEI particles were found to inhibit MDA-MB-231 breast and H1299 cancer cell growth depending on amount of PEI in p(HA)-PEI particles. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

    Yang, Ming-Hui; Chen, Ko-Chin; Chiang, Pei-Wen; Chung, Tze-Wen; Chen, Wan-Jou; Chu, Pei-Yu; Chen, Sharon Chia-Ju; Lu, Yi-Shan; Yuan, Cheng-Hui; Wang, Ming-Chen; Lin, Chia-Yang; Huang, Ying-Fong; Jong, Shiang-Bin; Lin, Po-Chiao; Tyan, Yu-Chang

    2016-01-01

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

  10. Hyaluronic Acid-Based Hydrogels: from a Natural Polysaccharide to Complex Networks

    PubMed Central

    Xu, Xian; Jha, Amit K.; Harrington, Daniel A.; Farach-Carson, Mary C.; Jia, Xinqiao

    2012-01-01

    Hyaluronic acid (HA) is one of nature's most versatile and fascinating macromolecules. Being an essential component of the natural extracellular matrix (ECM), HA plays an important role in a variety of biological processes. Inherently biocompatible, biodegradable and non-immunogenic, HA is an attractive starting material for the construction of hydrogels with desired morphology, stiffness and bioactivity. While the interconnected network extends to the macroscopic level in HA bulk gels, HA hydrogel particles (HGPs, microgels or nanogels) confine the network to microscopic dimensions. Taking advantage of various scaffold fabrication techniques, HA hydrogels with complex architecture, unique anisotropy, tunable viscoelasticity and desired biologic outcomes have been synthesized and characterized. Physical entrapment and covalent integration of hydrogel particles in a secondary HA network give rise to hybrid networks that are hierarchically structured and mechanically robust, capable of mediating cellular activities through the spatial and temporal presentation of biological cues. This review highlights recent efforts in converting a naturally occurring polysaccharide to drug releasing hydrogel particles, and finally, complex and instructive macroscopic networks. HA-based hydrogels are promising materials for tissue repair and regeneration. PMID:22419946

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

    PubMed

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

    2011-06-10

    A strategy has been designed to develop hyaluronic acid (HA) hydrogel for in vivo bone augmentation using minimal invasive technique. A mild synthetic procedure was developed to prepare aldehyde modified HA by incorporating an amino-glycerol side chain via amidation reaction and selective oxidation of the pendent group. This modification, upon mixing with hydrazide modified HA formed hydrazone-crosslinked hydrogel within 30s that was stable at physiological pH. In vitro experiments showed no cytotoxicity of hydrogel with the controlled release of active bone morphogenic protein-2 (BMP-2). In vivo evaluation of this gel as a BMP-2 carrier was performed by injecting gels over the rat calvarium and showed bone formation in 8 weeks in correlation with the amount of BMP-2 loaded (0, 1 and 30μg) within the gel. Furthermore, hydrogels with 30μg of BMP-2 induced less bone formation upon subcutaneous injection in comparison with subperiosteal implantation. Histological examination showed newly formed bone with a high expression of osteocalcin, osteopontin and with angiogenic bone marrow when higher BMP-2 concentration was employed. Our result suggests that novel HA hydrogels could be used as a BMP-2 carrier and can promote bone augmentation for potential orthopedic applications. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis

    PubMed Central

    2013-01-01

    Background Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model. Results Thirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity. Conclusion Overall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy. PMID:23574696

  13. Structural and rheological characterization of hyaluronic acid-based scaffolds for adipose tissue engineering.

    PubMed

    Borzacchiello, Assunta; Mayol, Laura; Ramires, Piera A; Pastorello, Andrea; Di Bartolo, Chiara; Ambrosio, Luigi; Milella, Evelina

    2007-10-01

    In this study the attention has been focused on the ester derivative of hyaluronic acid (HA), HYAFF11, as a potential three-dimensional scaffold in adipose tissue engineering. Different HYAFF11 sponges having different pore sizes, coated or not coated with HA, have been studied from a rheological and morphological point of view in order to correlate their structure to the macroscopic and degradation properties both in vitro and in vivo, using rat model. The in vitro results indicate that the HYAFF11 sponges possess proper structural and mechanical properties to be used as scaffolds for adipose tissue engineering and, among all the analysed samples, uncoated HYAFF11 large-pore sponges showed a longer lasting mechanical stability. From the in vivo results, it was observed that the elastic modulus of scaffolds seeded with preadipocytes, the biohybrid constructs, and explanted after 3 months of implantation in autologous rat model are over one order of magnitude higher than the corresponding values for the native tissue. These results could suggest that the implanted scaffolds can be invaded and populated by different cells, not only adipocytes, that can produce new matrix having different properties from that of adipose tissue.

  14. Biocompatible hyaluronic acid polymer-coated quantum dots for CD44+ cancer cell-targeted imaging

    NASA Astrophysics Data System (ADS)

    Wang, Hening; Sun, Hongfang; Wei, Hui; Xi, Peng; Nie, Shuming; Ren, Qiushi

    2014-10-01

    The cysteamine-modified hyaluronic acid (HA) polymer was employed to coat quantum dots (QDs) through a convenient one-step reverse micelle method, with the final QDs hydrodynamic size of around 22.6 nm. The HA coating renders the QDs with very good stability in PBS for more than 140 days and resistant to large pH range of 2-12. Besides, the HA-coated QDs also show excellent fluorescence stability in BSA-containing cell culture medium. In addition, the cell culture assay indicates no significant cytotoxicity for MD-MB-231 breast cancer cells, and its targeting ability to cancer receptor CD44 has been demonstrated on two breast cancer cell lines. The targeting mechanism was further proved by the HA competition experiment. This work has established a new approach to help solve the stability and toxicity problems of QDs, and moreover render the QDs cancer targeting property. The current results indicate that the HA polymer-coated QDs hold the potential application for both in vitro and in vivo cancer imaging researches.

  15. Sustained Small Molecule Delivery from Injectable Hyaluronic Acid Hydrogels through Host-Guest Mediated Retention

    PubMed Central

    Mealy, Joshua E.; Rodell, Christopher B.; Burdick, Jason A.

    2015-01-01

    Self-assembled and injectable hydrogels have many beneficial properties for the local delivery of therapeutics; however, challenges still exist in the sustained release of small molecules from these highly hydrated networks. Host-guest chemistry between cyclodextrin and adamantane has been used to create supramolecular hydrogels from modified polymers. Beyond assembly, this chemistry may also provide increased drug retention and sustained release through the formation of inclusion complexes between drugs and cyclodextrin. Here, we engineered a two-component system from adamantane-modified and β-cyclodextrin (CD)-modified hyaluronic acid (HA), a natural component of the extracellular matrix, to produce hydrogels that are both injectable and able to sustain the release of small molecules. The conjugation of cyclodextrin to HA dramatically altered its affinity for hydrophobic small molecules, such as tryptophan. This interaction led to lower molecule diffusivity and the release of small molecules for up to 21 days with release profiles dependent on CD concentration and drug-CD affinity. There was significant attenuation of release from the supramolecular hydrogels (~20% release in 24h) when compared to hydrogels without CD (~90% release in 24h). The loading of small molecules also had no effect on hydrogel mechanics or self-assembly properties. Finally, to illustrate this controlled delivery approach with clinically used small molecule pharmaceuticals, we sustained the release of two widely used drugs (i.e., doxycycline and doxorubicin) from these hydrogels. PMID:26693019

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

    NASA Astrophysics Data System (ADS)

    Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

    2012-12-01

    In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

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

    PubMed Central

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

    2015-01-01

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

  18. 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.

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

    PubMed

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

    2016-06-25

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

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

    PubMed

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

    2013-01-02

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

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

    PubMed

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

    2013-07-17

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

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

    PubMed

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

    2015-10-20

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

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

    PubMed

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

    2016-03-01

    Extracellular matrix (ECM) degradation, one of the main features of osteoarthritis, is driven by at least two major classes of enzymes: matrix metalloproteases (MMPs) and hyaluronidases. Among certain glycosaminoglycans, including natural and chemically cross-linked HAs, which are currently used as viscosupplements, the hyaluronic acid (HA) alkyl-amides (Hyadd) were here selected as the strongest MMP and hyaluronidase inhibitors. We used C. histolyticum collagenase (ChC) and bovine testicular hyaluronidase (BTH) as representative models of human MMPs and hyaluronidases, respectively. The role of the alkyl moiety was investigated using HA derivatives with varying alkyl lengths and degrees of derivatization. The selected compound was then screened against 10 different human MMPs in vitro, and the results were validated ex vivo in human synovial fluid. Hyadd-C16, identified as a lead compound, showed the highest inhibition potency against MMP13 and MMP8. The in vitro results were confirmed by the inhibition of human MMP13 (Ki=106.1 μM) and hyaluronidase-2 in the synovial fluid of patients with osteoarthritis. This study demonstrates the unique properties of Hyadd-C16, including its remarkable enzymatic inhibitory activity, which is conferred by the hydrophobic chain, and its high biocompatibility and water solubility of the HA backbone. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Blinded evaluation of the effects of hyaluronic acid filler injections on first impressions.

    PubMed

    Dayan, Steven H; Arkins, John P; Gal, Thomas J

    2010-11-01

    Facial appearance has profound influence on the first impression that is projected to others. To determine the effects that complete correction of the nasolabial folds (NLFs) with hyaluronic acid (HA) filler has on the first impression one makes. Twenty-two subjects received injections of HA filler into the NLFs. Photographs of the face in a relaxed pose were taken at baseline, optimal correction visit, and 4 weeks after optimal correction. Three hundred four blinded evaluators completed a survey rating first impression on various measures of success for each photo. In total, 5,776 first impressions were recorded, totaling 46,208 individual assessments of first impression. Our findings indicate a significant improvement in mean first impression in the categories of dating success, attractiveness, financial success, relationship success, athletic success, and overall first impression at the optimal correction visit. At 4 weeks after the optimal correction visit, significance was observed in all categories measured: social skills, academic performance, dating success, occupational success, attractiveness, financial success, relationship success, athletic success, and overall first impression. Full correction of the NLFs with HA filler significantly and positively influences the first impression an individual projects. © 2010 by the American Society for Dermatologic Surgery, Inc.

  5. Enzyme responsive hyaluronic acid nanocapsules containing polyhexanide and their exposure to bacteria to prevent infection.

    PubMed

    Baier, Grit; Cavallaro, Alex; Vasilev, Krasimir; Mailänder, Volker; Musyanovych, Anna; Landfester, Katharina

    2013-04-08

    Antibacterial nanodevices could bring coatings of plastic materials and wound dressings a big step forward if the release of the antibacterial agents could be triggered by the presence of the bacteria themselves. Here, we show that novel hyaluronic acid (HA)-based nanocapsules containing the antimicrobial agent polyhexanide are specifically cleaved in the presence of hyaluronidase, a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus and Escherichia coli. This resulted in an efficient killing of the pathogenic bacteria by the antimicrobial agent. The formation of different polymeric nanocapsules was achieved through a polyaddition reaction in inverse miniemulsion. After the synthesis, the nanocapsules were transferred to an aqueous medium and investigated in terms of size, size distribution, functionality, and morphology using dynamic light scattering, zeta potential measurements and scanning electron microscopy. The enzyme triggered release of a model dye and the antimicrobial polyhexanide was monitored using fluorescence and UV spectroscopy. The stability of the nanocapsules in several biological media was tested and the interaction of nanocapsules with human serum protein was studied using isothermal titration calorimetry. The antibacterial effectiveness is demonstrated by determination of the antibacterial activity and determination of the minimal bactericidal concentration (MBC).

  6. Polyethylene oxide (PEO)-hyaluronic acid (HA) nanofibers with kanamycin inhibits the growth of Listeria monocytogenes.

    PubMed

    Ahire, J J; Robertson, D D; van Reenen, A J; Dicks, L M T

    2017-02-01

    Listeria monocytogenes is well known to cause prosthetic joint infections in immunocompromised patients. In this study, polyethylene oxide (PEO) nanofibers, containing kanamycin and hyaluronic acid (HA), were prepared by electrospinning at a constant electric field of 10kV. PEO nanofibers spun with 0.2% (w/v) HA and 1% (w/v) kanamycin had a smooth, bead-free structure at 30-35% relative humidity. The average diameter of the nanofibers was 83±20nm. Attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy indicated that kanamycin was successfully incorporated into PEO/HA matrix. The presence of kanamycin affects the thermal properties of PEO/HA nanofibers, as shown by differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The kanamycin-PEO-HA nanofibers (1mg; 47±3μg kanamycin) inhibited the growth of L. monocytogenes EDGe by 62%, as compared with PEO-HA nanofibers, suggesting that it may be used to coat prosthetic implants to prevent secondary infections.

  7. Water soluble complexes of chitosan-g-MPEG and hyaluronic acid.

    PubMed

    Wu, Jun; Wang, Xuefen; Keum, Jong Kahk; Zhou, Hongwen; Gelfer, Mikhail; Avila-Orta, Carlos-Alberto; Pan, Hui; Chen, Weiliam; Chiao, Shu-Min; Hsiao, Benjamin S; Chu, Benjamin

    2007-03-15

    Novel water soluble, biocompatible, and highly viscoelastic polyelectrolyte complexes were prepared by mixing of positively charged chitosan grafted with poly (ethylene glycol) monomethyl ether (CS-g-MPEG) and negatively charged hyaluronic acid (HA). CS-g-MPEGs having different degrees of substitution were synthesized by reacting chitosan with MPEG-aldehyde. The molecular structure, thermal and rheological properties, as well as biocompatibility of CS-g-MPEG/HA complexes were characterized. Rheological results showed that a small amount of HA could greatly enhance the viscosity of CS-g-MPEG solution. The highest viscosity was obtained when the charge ratio of CS-g-MPEG/HA was close to 1.0. Small-angle X-ray scattering measurements provided some insights into the lamellar structure of the CS-g-MPEG/HA complex. The CS-g-MPEG/HA complex system offers promising potentials in pharmaceutical, cosmetic, and biotechnology applications (e.g., cell scaffold, artificial synovial fluid, and drug/gene delivery medium).

  8. Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery

    NASA Astrophysics Data System (ADS)

    Hayward, Stephen L.; Francis, David M.; Sis, Matthew J.; Kidambi, Srivatsan

    2015-10-01

    The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.

  9. Novel crosslinked alginate/hyaluronic acid hydrogels for nerve tissue engineering

    NASA Astrophysics Data System (ADS)

    Wang, Min-Dan; Zhai, Peng; Schreyer, David J.; Zheng, Ruo-Shi; Sun, Xiao-Dan; Cui, Fu-Zhai; Chen, Xiong-Biao

    2013-09-01

    Artificial tissue engineering scaffolds can potentially provide support and guidance for the regrowth of severed axons following nerve injury. In this study, a hybrid biomaterial composed of alginate and hyaluronic acid (HA) was synthesized and characterized in terms of its suitability for covalent modification, biocompatibility for living Schwann cells and feasibility to construct three dimensional (3D) scaffolds. Carbodiimide mediated amide formation for the purpose of covalent crosslinking of the HA was carried out in the presence of calciumions that ionically crosslink alginate. Amide formation was found to be dependent on the concentrations of carbodiimide and calcium chloride. The double-crosslinked composite hydrogels display biocompatibility that is comparable to simple HA hydrogels, allowing for Schwann cell survival and growth. No significant difference was found between composite hydrogels made from different ratios of alginate and HA. A 3D BioPlotter™ rapid prototyping system was used to fabricate 3D scaffolds. The result indicated that combining HA with alginate facilitated the fabrication process and that 3D scaffolds with porous inner structure can be fabricated from the composite hydrogels, but not from HA alone. This information provides a basis for continuing in vitro and in vivo tests of the suitability of alginate/HA hydrogel as a biomaterial to create living cell scaffolds to support nerve regeneration.

  10. Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Liopo, Anton; Su, Richard; Tsyboulski, Dmitri A.; Oraevsky, Alexander A.

    2016-08-01

    Enhanced delivery of optical clearing agents (OCA) through skin may improve sensitivity of optical and optoacoustic (OA) methods of imaging, sensing, and monitoring. This report describes a two-step method for enhancement of light penetration through skin. Here, we demonstrate that topical application of hyaluronic acid (HA) improves skin penetration of hydrophilic and lipophilic OCA and thus enhances their performance. We examined the OC effect of 100% polyethylene and polypropylene glycols (PPGs) and their mixture after pretreatment by HA, and demonstrated significant increase in efficiency of light penetration through skin. Increased light transmission resulted in a significant increase of OA image contrast in vitro. Topical pretreatment of skin for about 30 min with 0.5% HA in aqueous solution offers effective delivery of low molecular weight OCA such as a mixture of PPG-425 and polyethylene glycol (PEG)-400. The developed approach of pretreatment by HA prior to application of clearing agents (PEG and PPG) resulted in a ˜47-fold increase in transmission of red and near-infrared light and significantly enhanced contrast of OA images.

  11. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    PubMed Central

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor. PMID:26213465

  13. Association between Hyaluronic Acid Injections and Time-to-Total Knee Replacement Surgery.

    PubMed

    Altman, Roy; Fredericson, Michael; Bhattacharyya, Samir K; Bisson, Brad; Abbott, Thomas; Yadalam, Sashidhar; Kim, Myoung

    2016-10-01

    This study assessed the association between hyaluronic acid (HA) injections and time-to-total knee replacement (TKR) surgery for patients with knee osteoarthritis (OA). Patients 18 to 64 years of age who had TKR surgery between January 1, 2006 and December 31, 2011 were identified from the MarketScan Commercial claims database. All patients had 6 years or more of continuous enrollment prior to TKR surgery. There were two cohorts (1) patients with HA injections prior to TKR surgery and (2) patients who did not have HA injections prior to TKR surgery. Time-to-TKR was defined as the total days from the date of diagnosis of knee OA on the patient's first visit to an orthopedic surgeon to the date of TKR surgery. Results included 22,555 patients who had TKR surgery: 14,132 in the non-HA and 8,423 in the HA cohort. In this retrospective analysis of patients undergoing TKR, the median Time-to-TKR surgery was 326 days for the non-HA and 908 days for the HA cohort, a difference of 582 days. Those receiving HA injections had a median 1.6-year longer Time-to-TKR surgery versus those who did not receive HA injections. These results have both clinical and economic implications.

  14. Biodynamic performance of hyaluronic acid versus synovial fluid of the knee in osteoarthritis.

    PubMed

    Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

    2015-08-01

    Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model that can be evaluated for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, a comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA (Singh et al., 2014).

  15. Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes.

    PubMed

    Salamanna, F; Frizziero, A; Pagani, S; Giavaresi, G; Curzi, D; Falcieri, E; Marini, M; Abruzzo, P M; Martini, L; Fini, M

    2015-02-01

    The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenocytes. Twenty-four male Sprague-Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1β, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1β was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.

  16. Matrices of a hydrophobically functionalized hyaluronic acid derivative for the locoregional tumour treatment.

    PubMed

    Palumbo, Fabio Salvatore; Puleio, Roberto; Fiorica, Calogero; Pitarresi, Giovanna; Loria, Guido Ruggero; Cassata, Giovanni; Giammona, Gaetano

    2015-10-01

    A hyaluronic acid (HA) derivative bearing octadecylamine and acylhydrazine functionalities has been here employed for the production of a paclitaxel delivering matrix for locoregional chemotherapy. Through a strategy consisting in a powder compression and a plasticization with a mixture water/ethanol, a physically assembled biomaterial, stable in solutions with physiologic ionic strengths, has been produced. Two different drug loading strategies have been adopted, by using paclitaxel as chemotherapic agent, and obtained samples have been assayed in terms of release in enhanced solubility conditions and in vitro and in vivo tumoural cytotoxicity. In particular sample with the best releasing characteristics was chosen for an in vivo evaluation against a HCT-116 xenograft on mice. Local tumour establishment and metastatic diffusion was assayed locally at the site of xenograft implantation and at the tributary lymph nodes. Obtained results demonstrated how loading procedure influenced paclitaxel crystallinity into the matrix and consequently drug diffusion and its cytoreductive potential. Chosen paclitaxel loaded matrix was able to drastically inhibit HCT-116 establishment and metastatic diffusion.

  17. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

    PubMed

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

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

    PubMed

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

    2015-03-01

    Natural polysaccharides are extensively investigated as cell scaffold materials for cellular adhesion, proliferation, and differentiation due to their excellent biocompatibility, biodegradability, and biofunctions. However, their application is often severely limited by their mechanical behavior. In this study, a tough and elastic hydrogel scaffold was prepared with hyaluronic acid (HA) and chondroitin sulfate (CS). HA and CS were conjugated with tyramine (TA) and the degree of substitution (DS) was 10.7% and 11.3%, respectively, as calculated by (1)H NMR spectra. The hydrogel was prepared by mixing HA-TA and CS-TA in presence of H2O2 and HRP. The sectional morphology of hydrogels was observed by SEM, static and dynamic mechanical properties were analyzed by Shimadzu electromechanical testing machine and dynamic mechanical thermal analyzer Q800. All samples showed good ability to recover their appearances after deformation, the storage modulus (E') of hydrogels became higher as the testing frequency went up. Hydrogels also showed fatigue resistance to cyclic compression. Mesenchymal stem cells encapsulated in hydrogels showed good cell viability as detected by CLSM. This study suggests that the hydrogels have both good mechanical properties and biocompatibility, and may serve as model systems to explore mechanisms of deformation and energy dissipation or find some applications in tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Clinical Application of Earlobe Augmentation with Hyaluronic Acid Filler in the Chinese Population.

    PubMed

    Qian, Wei; Zhang, Yan-Kun; Cao, Qian; Hou, Ying; Lv, Wei; Fan, Ju-Feng

    2017-02-01

    Larger earlobes, which are a symbol of "richness" in traditional Chinese culture, are favored by Chinese patients. The objective of this paper is to investigate the application of earlobe augmentation with hyaluronic acid (HA) filler injection and its clinical effects in the Chinese population. A total of 19 patients (38 ears) who received earlobe augmentation with HA filler injections between March 2013 and March 2015 were included. The clinical effects, duration, and complications of these cases were investigated. All patients who received earlobe HA injections showed immediate postoperative effects with obvious morphological improvement of their earlobes. The volume of HA filler injected into each ear was 0.3-0.5 ml. The duration of the effect was 6-9 months. Two of the 19 cases (3 ears) demonstrated mild bruising at the injection site, but the bruising completely disappeared within 7 days after the injection. No vascular embolism, infection, nodule, or granuloma complications were observed in the studied group. The application of earlobe augmentation with HA filler injection is a safe, effective, simple procedure for earlobe shaping. It has an easy clinical application with good clinical prospects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  20. The efficacy, longevity, and safety of combined radiofrequency treatment and hyaluronic Acid filler for skin rejuvenation.

    PubMed

    Kim, Hyuk; Park, Kui Young; Choi, Sun Young; Koh, Hyun-Ju; Park, Sun-Young; Park, Won-Seok; Bae, Il-Hong; Kim, Beom Joon

    2014-08-01

    Recent advances in hyaluronic acid (HA) fillers and radiofrequency (RF) devices have been made in the context of skin rejuvenation and cosmetic surgery. Moreover, combination regimens with both techniques are currently being developed. The present study was designed to examine the clinical and histologic effects of a new needle that incorporates an RF device for HA injections. A new intradermal needle RF device (INNOfill; Pacific Pharma, Korea) was assessed in the present study. In the animal arm, procollagen production was measured by using enzyme-linked immunosorbent assay, the filler volume was quantified by incorporating a dye with filler, and the filler distribution was assessed through the changes in tissue structure. In the human arm, the efficacy of the combination regimen was assessed by using the wrinkle severity rating scale (WSRS). In the animal study, RF treatment increased procollagen production in a time-dependent fashion. The total volume was significantly increased with the RF treatment when compared with the filler injections alone, and lasted for up to 7 weeks after treatment. Additionally, the filler distribution was reduced in animals treated with RF when compared with the untreated group. In the human study, the nasolabial folds of subjects treated with RF before filler injections exhibited a significantly greater change in the WSRS score from baseline when compared with the nasolabial folds treated with filler injections alone. A new device incorporating RF treatment before HA filler injection may represent a biocompatible and long-lasting advance in skin rejuvenation.

  1. The Kinetics of Reversible Hyaluronic Acid Filler Injection Treated With Hyaluronidase.

    PubMed

    Juhász, Margit L W; Levin, Melissa K; Marmur, Ellen S

    2017-06-01

    Hyaluronidase is an enzyme capable of dissolution of hyaluronic acid (HA). There is a lack of evidence-based research defining time- and concentration-dependent reversal of HA filler using hyaluronidase. To explore the efficacy of different concentrations of hyaluronidase in digesting commercially available HA-based reversible fillers-Belotero Balance (BEL), Juvederm Ultra XC (JUVXC), Juvederm Ultra Plus (JUVX+), Juvederm Voluma XC (JUVV), Restylane-L (RESL), Restylane Silk (RESS), and Perlane/Restylane Lyft (RESLYFT). This was a blinded randomized study involving 15 participants. Participants received HA filler injection into their back, followed by no secondary injection, or injection with normal saline, 20 or 40 units of hyaluronidase. Using a 5-point palpation scale, the degradation of HA filler was monitored over 14 days. In the authors' study, there is a significant decrease in HA filler degradation using 20 and 40 units of hyaluronidase compared with no secondary injection or normal saline. There is no significant difference in HA filler dissolution when comparing 20 to 40 units of hyaluronidase. Lower concentrations of hyaluronidase may be just as effective as higher concentrations to degrade HA filler in situations where the reversal of cutaneous augmentation with HA filler arises.

  2. Biological properties of a new volumizing hyaluronic acid filler: a systematic review.

    PubMed

    Ho, Derek; Jagdeo, Jared

    2015-01-01

    Hyaluronic acid (HA) dermal fillers are effective and safe for correction of facial rhytides. A new volumizing HA filler, 20 mg/ml HA dermal filler (Juvéderm® Voluma®, Allergan Inc., Irvine, CA), is the only HA filler with a FDA indication for facial volumization due to age-related facial volume loss. Evaluate the biological properties, including biochemical, biophysical and rheological, of this new 20 mg/ml HA dermal filler and discuss the importance of these properties in clinical applications. A systematic search of the computerized bibliographic databases Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation Abstracts with key term "Voluma." Four articles on the biological properties of this new 20 mg/ ml HA dermal filler were suitable for inclusion in this review. Biological analysis of elasticity and viscosity values of this new 20 mg/ml HA dermal filler demonstrated intermediate properties in three studies and high in one study compared to other HA dermal fillers. This 20 mg/ml HA dermal filler retained the highest elasticity and viscosity values at temperature of 37°C. Histology demonstrated that this 20 mg/ml HA dermal filler has an intermediate pattern of distribution within the superficial and deep reticular dermis. This 20 mg/ml HA dermal filler demonstrated volumizing ability, and maintaining viscosity and free-flowing characteristics for easy injection, tissue lifting, and molding. We hope future research incorporates biological properties analysis of this HA dermal filler in clinical trials.

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

    PubMed

    Andre, Pierre

    2004-12-01

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

  4. Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic rabbit knee joints.

    PubMed

    Lindenhayn, K; Heilmann, H H; Niederhausen, T; Walther, H U; Pohlenz, K

    1997-05-01

    The half-life of [3H]hyaluronic acid in rabbit knee joints was estimated using two methods: (i) by following the [3H]hyaluronan content of the synovial fluid after intra-articular injection and (ii) by following the 3H2O radioactivity of plasma after intra-articular injection of [3H]hyaluronan. For normal rabbits we obtained a half-life of 15.8 hours (method I) and 17.5 +/- 1.0 hours (mean +/- SEM, method II), respectively. The second method was used to estimate the kinetics of the hyaluronan elimination from normal, sham-operated, as well as from osteoarthritic rabbit knee joints (Colombo model of osteoarthritis). Four weeks after injury, during the developing phase of osteoarthritis, the half-life of hyaluronan rose significantly to 23.5 +/- 2.1 hours and returned to normal levels (17.4 +/- 2.7 hours) 12 weeks after the operation (osteoarthritis developed). At the stage of developed osteoarthritis, the clearance rates were considerably higher than in normal rabbits.

  5. Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

    NASA Astrophysics Data System (ADS)

    Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

    2017-05-01

    Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

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

    PubMed

    Tokatlian, Talar; Cam, Cynthia; Segura, Tatiana

    2015-05-01

    The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect. Here, 100 and 60 μm porous and nonporous (n-pore) hyaluronic acid-MMP hydrogels with encapsulated reporter (pGFPluc) or proangiogenic (pVEGF) plasmids are used to investigate scaffold-mediated gene delivery for local gene therapy in a diabetic wound healing mouse model. Porous hydrogels allow for significantly faster wound closure compared with n-pore hydrogels, which do not degrade and essentially provide a mechanical barrier to closure. Interestingly, the delivery of pDNA/PEI polyplexes positively promotes granulation tissue formation even when the DNA does not encode for an angiogenic protein. And although transfected cells are present throughout the granulation tissue surrounding, all hydrogels at 2 weeks, pVEGF delivery does not further enhance the angiogenic response. Despite this, the presence of transfected cells shows promise for the use of polyplex-loaded porous hydrogels for local gene delivery in the treatment of diabetic wounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Subureteral Injection with Small-Size Dextranomer/Hyaluronic Acid Copolymer: Is It Really Efficient?

    PubMed Central

    Tan, Özgür; Farahvash, Amirali; Senol, Cem; Gümüstas, Hüseyin; Atay, Irfan; Deniz, Nuri

    2016-01-01

    The aim of this study was to evaluate the clinical results of patients with vesicoureteral reflux, which were treated with subureteral injection of small-size (80–120 μm) dextranomer/hyaluronic acid copolymer (Dx/HA). Data of 75 children (105 renal units) who underwent STING procedure with small-size Dx/HA for the treatment of vesicoureteral reflux (VUR) in our clinic between 2008 and 2012 were retrospectively analyzed. Preoperative reflux grade and side, injection indication, postoperative urinary infections and urinary symptoms, voiding cystourethrogram, and renal scintigraphy results were evaluated. The success rate of the procedure was 100% in patients with grades 1 and 2 reflux, 91% in patients with grade 3 reflux, and 82.6% in patients with grade 4. Overall success rate of the treated patients was 97%. Endoscopic subureteric injection with Dx/HA procedure has become a reasonable minimally invasive alternative technique to open surgery, long-term antibiotic prophylaxis, and surveillance modalities in treatment of VUR in terms of easy application, low costs and complication rates, and high success rates. Injection material composed of small-size dextranomer microspheres seems superior to normal size Dx/HA, together with offering similar success with low cost. PMID:28105412

  8. Stiffness and Adhesivity Control Aortic Valve Interstitial Cell Behavior within Hyaluronic Acid Based Hydrogels

    PubMed Central

    Duan, Bin; Hockaday, Laura A.; Kapetanovic, Edi; Kang, Kevin H.; Butcher, Jonathan T.

    2013-01-01

    Bioactive and biodegradable hydrogels that mimic the extracellular matrix and regulate valve interstitial cells (VIC) behavior are of great interest as three dimensional (3D) model systems for understanding mechanisms of valvular heart disease pathogenesis in vitro and the basis for regenerative templates for tissue engineering. However, the role of stiffness and adhesivity of hydrogels in VIC behavior remains poorly understood. This study reports synthesis of oxidized and methacrylated hyaluronic acid (Me-HA and MOHA) and subsequent development of hybrid hydrogels based on modified HA and methacrylated gelatin (Me-Gel) for VIC encapsulation. The mechanical stiffness and swelling ratio of the hydrogels were tunable with molecular weight of HA and concentration/composition of precursor solution. The encapsulated VIC in pure HA hydrogels with lower mechanical stiffness showed more spreading morphology comparing to stiffer counterparts and dramatically upregulated alpha smooth muscle actin expression indicating more activated myofibroblast properties. The addition of Me-Gel in Me-HA facilitated cell spreading, proliferation and VIC migration from encapsulated spheroids and better maintained VIC fibroblastic phenotype. The VIC phenotype transition during migration from encapsulated spheroids in both Me-HA and Me-HA/Me-Gel hydrogel matrix was also observed. These findings are important for the rational design of hydrogels for controlling VIC morphology, and for regulating VIC phenotype and function. The Me-HA/Me-Gel hybrid hydrogels accommodated with VIC are promising as valve tissue engineering scaffolds and 3D model for understanding valvular pathobiology. PMID:23648571

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

    PubMed

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

    2016-02-01

    Crosslinked injectable hyaluronic acid (HA)-gelatin (Ge) hydrogels have remarkable viscoelastic and biological properties for vocal fold tissue engineering. Patient-specific tuning of the viscoelastic properties of this injectable biomaterial could improve tissue regeneration. The frequency-dependent viscoelasticity of crosslinked HA-Ge hydrogels was measured as a function of the concentration of HA, Ge, and crosslinker. Synthetic extracellular matrix hydrogels were fabricated using thiol-modified HA and Ge, and crosslinked by poly(ethylene glycol) diacrylate. A recently developed characterization method based on Rayleigh wave propagation was used to quantify the frequency-dependent viscoelastic properties of these hydrogels, including shear storage and loss moduli, over a broad frequency range; that is, from 40 to 4000 Hz. The viscoelastic properties of the hydrogels increased with frequency. The storage and loss moduli values and the rate of increase with frequency varied with the concentrations of the constituents. The range of the viscoelastic properties of the hydrogels was within that of human vocal fold tissue obtained from in vivo and ex vivo measurements. Frequency-dependent parametric relations were obtained using a linear least-squares regression. The results are useful to better fine-tune the storage and loss moduli of HA-Ge hydrogels by varying the concentrations of the constituents for use in patient-specific treatments. © 2015 Wiley Periodicals, Inc.

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

    PubMed

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

    2010-12-01

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

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

    PubMed

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

    2008-12-01

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

  12. Clinical value of persistent but downgraded vesicoureteral reflux after dextranomer/hyaluronic acid injection in children.

    PubMed

    Baek, Minki; Kang, Min Young; Lee, Hahn-Ey; Park, Kwanjin; Choi, Hwang

    2013-07-01

    We aimed to investigate the clinical value of persistent but downgraded vesicoureteral reflux (VUR) after dextranomer/hyaluronic acid (Dx/HA) injection in children. The medical records of 128 children (195 ureters) who underwent Dx/HA injections for VUR were reviewed. The incidences of pre- and post-operative febrile urinary tract infections (UTIs) were analyzed in children with or without persistent VUR on voiding cystourethrography (VCUG) 3 months postoperatively. The surgical results of VUR persistent children who underwent a single additional injection were assessed. The VUR resolved completely in 100 ureters (51.3%), was persistent in 95 ureters, and newly developed in 2 ureters. The incidence of pre/post-operative febrile UTIs were 0.35 ± 0.39 per year and 0.07 ± 0.32 per year in VUR resolved children (P < 0.001), and 0.76 ± 1.18 per year and 0.20 ± 0.61 per year in VUR persistent children (P < 0.001). A single additional Dx/HA injection (44 ureters) resolved VUR in 29 ureters (65.9%), and also reduced the VUR to grade I in 7 ureters (15.9%), II in 4 (9.1%), and III in 4 (9.1%). Even in children with persistent VUR after Dx/HA injection, the incidence of febrile UTIs decreased markedly. The VUR grade significantly decreases after single additional Dx/HA injection.

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

    PubMed

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

    2017-02-15

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2015-07-01

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

  16. On the thickness uniformity of micropatterns of hyaluronic acid in a soft lithographic molding method

    NASA Astrophysics Data System (ADS)

    Jeong, Hoon Eui; Suh, Kahp Y.

    2005-06-01

    A soft lithographic molding is a simple and yet robust method for fabricating well-defined microstructures of a hydrophilic biopolymer such as polyethylene glycol and polysaccharide over a large area. The method consists of three steps: placing a polydimethylsiloxane mold with a bas-relief pattern onto a drop-dispensed polymer solution typically dissolved in water, letting the mold and the solution undisturbed in contact until solvent evaporates completely, and leaving behind a polymer replica after mold removal. In such a molding process, water can only evaporate from the edges of the mold due to impermeable nature of polydimethylsiloxane to water, resulting in a nonuniform distribution of film thickness or pattern height. Here we examine systematically how the evaporation rate affects the thickness distribution of the resulting microstructures by evaporating the solution of hyaluronic acid in various conditions. To compare with a theory, we also present a simple theoretical model based on one-dimensional conservation equation for a liquid film, which is in good agreement with the experimental data.

  17. Resurfacing with Chemically Modified Hyaluronic Acid and Lubricin for Flexor Tendon Reconstruction

    PubMed Central

    Zhao, Chunfeng; Hashimoto, Takahiro; Kirk, Ramona L.; Thoreson, Andrew R.; Jay, Gregory D.; Moran, Steven L.; An, Kai-Nan; Amadio, Peter C.

    2013-01-01

    We assessed surface coating with carbodiimide derivatized hyaluronic acid combined with lubricin (cd-HA-Lubricin) as a way to improve extrasynovial tendon surface quality and, consequently, the functional results in flexor tendon reconstruction, using a canine in vivo model. The second and fifth flexor digitorum profundus tendons from 14 dogs were reconstructed with autologs peroneus longus (PL) tendons 6 weeks after a failed primary repair. One digit was treated with cd-HA-Lubricin, and the other was treated with saline as the control. Six weeks following grafting, the digits and graft tendons were functionally and histologically evaluated. Adhesion score, normalized work of flexion, graft friction in zone II, and adhesion breaking strength at the proximal repair site in zone III were all lower in the cd-HA-Lubricin treated group compared to the control group. The strength at the distal tendon/bone interface was decreased in the cd-HA-Lubricin treated grafts compared to the control grafts. Histology showed inferior healing in the cd-HA-Lubricin group at both proximal and distal repair sites. However, cd-HA-Lubricin treatment did not result in any gap or rupture at either the proximal or distal repair sites. These results demonstrate that cd-HA-Lubricin can eliminate graft adhesions and improve digit function, but that treatment may have an adverse effect on tendon healing. PMID:23335124

  18. Biodynamic Performance of Hyaluronic Acid versus Synovial fluid of the Knee for Osteoarthritic Therapy

    PubMed Central

    Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

    2015-01-01

    Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model and evaluation for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, the comparison of different models with and without endogenous lubricating surface zone proteins, such as