Carboxyl Group Of Hyaluronic Acid Research Articles

An injectable hyaluronic acid-Polydeoxyribonucleotides (HA-PDRN) crosslinked hydrogel as a dermal filler

Injectable hydrogels, commonly utilized as dermal fillers, show great potential for increasing tissue volume and correcting wrinkles. HA (hyaluronic acid), extensively used in dermal fillers, requires considerable modifications to meet commercial demands for effectiveness and functionality. PDRN (polydeoxyribonucleotides), DNA extracted from salmon sperm cells, offer several therapeutic benefits, including anti-inflammatory and collagen stimulation. This work presents a new crosslinked hydrogel based on HA and PDRN. HA-PDRN crosslinked hydrogels were fabricated via covalent interactions between the carboxyl groups of HA and amino groups of PDRN, resulting in desirable properties such as viscoelasticity, appearance, hydration, degradation, injectability, and biocompatibility. In vivo studies on mice revealed that these hydrogels maintain volume for over 24 weeks, with reduced inflammation and enhanced collagen synthesis, as well as exhibiting durability, safety, and supportability.

Macrophage-Targeted GSH-Depleting Nanocomplexes for Synergistic Chemodynamic Therapy/Gas Therapy/Immunotherapy of Intracellular Bacterial Infection.

Intracellular pathogens can survive inside the macrophages to protect themselves from eradication by the innate immune system and conventional antibiotics, resulting in severe bacterial infections. In this work, an antibiotic-free nanocomplex (HA/GA-Fe@NO-DON), exhibiting macrophage-targeted synergistic gas therapy (nitric oxide, NO)/chemodynamic therapy/immunotherapy, was reported. HA/GA-Fe nanoparticles were synthesized by the strong coordination interactions among carboxyl groups of hyaluronic acid (HA), polyphenol groups of gallic acid (GA), and Fe(II) ions. The hydrophobic glutathione (GSH)-responsive NO donor (NO-DON) was encapsulated in HA/GA-Fe nanoparticles to form the final nanocomplexes (HA/GA-Fe@NO-DON). HA on the nanocomplexes guides the macrophage-specific uptake and intracellular accumulation. After the uptake, HA/GA-Fe@NO-DON nanocomplexes could not only generate highly toxic hydroxyl radicals (•OH) by the Fenton reaction and GSH depletion but also release NO when stimulated by intracellular GSH. Meanwhile, the nanocomplexes could trigger an efficient proinflammation immune response to reinforce the antibacterial activity. This work presents the development of antibiotic-free macrophage-targeted HA/GA-Fe@NO-DON nanocomplexes as an effective adjuvant nanomedicine with synergistic gas therapy/chemodynamic therapy/immunotherapy for eliminating intracellular bacterial infection.

3D Printable Polyelectrolyte Complex‐Integrated Interpenetrating Network Hydrogels with Customizable Mechanical Strength and pH‐Responsiveness

AbstractHerein, a novel 3D printable ink designed for the fabrication of interpenetrating polymer network (IPN) hydrogels is introduced, ingeniously integrating a polyelectrolyte complex (PEC) of hyaluronic acid (HA) and chitosan (CS) with a photo‐crosslinkable P(OEGMA‐co‐EGDEMA) polymer. Initially, the carboxyl group of HA is modified with a photo‐labile ortho‐nitrobenzyl group, preventing premature PEC formation during 3D ink formulation. Subsequent UV illumination via digital light processing (DLP) simultaneously triggers the photo‐deprotection of the carboxyl group of HA and the photopolymerization of OEGMA crosslinked hydrogel, together creating a PEC‐integrated IPN hydrogel. Comprehensive characterizations, including NMR, IR, UV/Vis, TGA, DSC, SEM, and mechanical tests are conducted to evaluate the structural, morphological, and rheological properties of these hydrogels. Furthermore, adjustments to the composition of the 3D ink enable the production of hydrogels with a spectrum of mechanical strength and elastic modulus ranging from 1 to 10 kPa. The resultant PEC‐IPN hydrogels display excellent flexibility, compressive strength, high strain tolerance, pH responsiveness, and thermal stability. In essence, the approach seamlessly merges natural polyelectrolytes with technological innovation to refine 3D ink production. This method could mark a pivotal advancement in the realm of 3D materials, unlocking numerous prospective applications.

Labeling of Polysaccharides with Biotin and Fluorescent Dyes

Examples of labeling polysaccharides at hydroxyl groups are described in this paper, which are especially in demand for molecules with a blocked reducing end. The protocols presented are suitable for the microscale synthesis of labeled polysaccharides that do not require a chromatography step for isolation. Examples of hydroxyl labeling include (1) direct modification with fluorescein isothiocyanate; (2) reaction with a fluorescein-dichlorotriazine derivative; (3) reaction with biotin-dichlorotriazine; (4) indirect two-step modification (given for glycosphingolipid) with glutaric anhydride followed by amidation with aminospacered BODIPY or SuCy5. The labeling of carboxyl groups of hyaluronic acid with BODIPY is also described. The staining of plant tissue sections with biotinylated polysaccharide versus being fluorescein labeled is compared.

Hyaluronan-colistin conjugates: Synthesis, characterization, and prospects for medical applications

The development of nanotechnology-based antibiotic delivery systems (nanoantibiotics) is an important challenge in the effort to combat microbial multidrug resistance. These systems have improved biopharmaceutical characteristics by increasing local bioavailability and reducing systemic toxicity and the number and frequency of drug side effects. Conjugation of low -molecular -weight antibacterial agents with natural polysaccharides is an effective strategy for developing optimal targeted delivery systems with programmed release and reduced cytotoxicity. This study describes the synthesis of conjugates of colistin (CT) and hyaluronic acid (HA) using carbodiimide chemistry to conjugate the amino groups of CT with the carboxyl groups of HA. The obtained polysaccharide carriers had a degree of substitution (DS) with CT molecules of 3–10 %, and the CT content was 129–377 μg/mg. The size of the fabricated particles was 300–600 nm; in addition, there were conjugates in the form of single macromolecules (30–50 nm). The ζ-potential of developed systems was about −20 mV. In vitro release studies at pH 7.4 and pH 5.2 showed slow hydrolysis of amide bonds, with a CT release of 1–5 % after 24 h. The conjugates retained antimicrobial activity depending on the DS: at DS 8 %, the minimum inhibitory concentration (MIC) of the conjugate corresponded to the MIC of free CT. The resulting systems also reduced CT nephrotoxicity by 20–50 %. These new conjugates of CT with HA are promising for the development of nanodrugs for safe and effective antimicrobial therapy.

A radiolabeled nanoparticle probe coated with hyaluronic acid via electrostatic interaction to diagnose CD44-positive tumors

CD44 is overexpressed in many tumors and is associated with tumor malignancy, including metastasis. Hyaluronic acid (HA) is a biocompatible polymer that specifically targets CD44-positive tumors. In this study, a ternary complex (charge ratio of carboxyl groups of indium-111 (111In)-labeled polyamidoamine dendrimer, amino groups of polyethyleneimine, and carboxyl groups of HA of 1:8:32) was successfully prepared using electrostatic interactions to develop a nuclear medical imaging probe for CD44-positive tumors. The particle size and zeta potential of the probe were 38.6 ± 1.3 nm and −31.6 ± 0.7 mV, respectively. The ternary HA complex was taken up by CD44-positive tumor cells via HA-specific pathway in vitro. Partial CD44-specific tumor uptake of the 111In-labeled HA complex occurred in tumor-bearing mice. The radiolabeled HA complex established by electrostatic interaction may be a nuclear medical imaging probe targeting CD44-positive tumors.

Adipose-Derived Stem Cell-Incubated HA-Rich Sponge Matrix Implant Modulates Oxidative Stress to Enhance VEGF and TGF-β Secretions for Extracellular Matrix Reconstruction In Vivo.

This study demonstrated both adipose-derived stem cells (ASCs) in vitro and in vivo combined with three-dimensional (3D) porous sponge matrices on implant wound healing. Sponge matrices were created from hyaluronic acid (HA), collagen (Col), and gelatin (Gel), constructing two types: HA-L (low content) and HA-H (high content), to be cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Fourier transform infrared spectroscopy method verified carboxyl groups of HA and amino groups of Col and Gel reacting between the raw materials and scaffolds to identify the successive cross-linking. The swelling ratios of two types of sponge matrices were analyzed by water absorption capabilities, and the results displayed both over 30-fold dry scaffold weight enhancements. In biodegradation tests, matrices were hydrolyzed over time by three cutaneous enzymes, hyaluronidase, lysozyme, and collagenase I. ASCs from rats were cultured within the HA-H scaffold, demonstrating higher antioxidative abilities and secretions on related genes and proteins compared to the other two groups. The ASC HA-H matrix promoted cell proliferation to stimulate capillary angiogenesis inducer secretions, including vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β). In vivo histological examinations showed ASCs from implanted HA-H implant transported into the subcutis, and rat skin cells also infiltrated into the original matrix zone to increase the extracellular matrix (ECM) reconstructions. Our experimental data revealed that the ASC HA-H sponge implant was effective in improving wound repair.

Hyaluronic acid coating on the surface of curcumin-loaded ZIF-8 nanoparticles for improved breast cancer therapy: An in vitro and in vivo study

Despite developments in surgery and chemotherapy, effective treatment of breast cancer is still an urgent problem owing to recurrence and metastasis. By combining the advantages of curcumin (Cur), zeolitic imidazolate framework-8 nanoparticles (ZIF-8), and hyaluronic acid (HA) in breast cancer therapy, Cur-loaded and HA-coated ZIF-8 (Cur@ZIF-8@HA) were synthesized using a method based on the pH-dependent solubility of Cur and the electrostatic interactions between zinc ions and carboxyl groups of HA. Cur@ZIF-8 were also prepared as a control group. Comprehensive comparisons of the physicochemical properties and anticancer activities of Cur@ZIF-8@HA and Cur@ZIF-8 were conducted. The results indicated that the degradation of Cur during the synthesis of Cur@ZIF-8 was negligible. The obtained Cur@ZIF-8 and Cur@ZIF-8@HA were truncated cubes with hydrodynamic diameters of 174 and 217 nm, respectively. Cur@ZIF-8@HA possessed better stability during storage in different media, a slower drug release rate under neutral and acidic conditions, and a greater inhibitory effect on breast cancer than Cur@ZIF-8. For 4T1 cells, treatment using Cur@ZIF-8@HA induced more cellular uptake and higher cytotoxicity, accompanied by higher lactate dehydrogenase release, cell cycle arrest in G2/M and S phases, production of reactive oxygen species, and apoptosis. In 4T1 tumor-bearing mice models, Cur@ZIF-8@HA showed a stronger inhibitory effect on tumor growth and pulmonary metastasis. Therefore, Cur@ZIF-8@HA might hold great potential as an agent for the effective therapy of breast cancer.

Layered hydroxide/polydopamine/hyaluronic acid functionalized magnesium alloys for enhanced anticorrosion, biocompatibility and antithrombogenicity in vascular stents.

Magnesium alloys are promising cardiovascular stent materials due to the favourable physical properties and complete biodegradability in vivo. However, the rapid degradation, poor cytocompatibility and tendency of thrombogenesis hinder practical clinical applications. In order to solve these problems, a facile and highly efficient strategy of alkali treatment combined with subsequent layer-by-layer assembly was used to fabricate a multifunctional coating. A bottom layer hydroxyl (–OH) with negative charge after alkali treatment first formed a solid bond with magnesium matrix to provide a rough outer surface for the further immobilization of functional biomolecules. Afterwards, polydopamine and hyaluronic acid were successively immobilized on alkali-treated magnesium surface via strong electrostatic adsorption and covalent bonding between carboxyl group of hyaluronic acid and amine or hydroxyl of polydopamine to form magnesium/OH/polydopamine/hyaluronic acid. Hydroxyl significantly improves the corrosion resistance while polydopamine and hyaluronic acid layers act as a further barrier to provide better anticorrosion. A balance between biocompatibility and antithrombogenicity has been achieved by adjusting the content of hyaluronic acid on polydopamine surface. The multifunctional magnesium/OH/polydopamine/hyaluronic acid coating with lower hyaluronic acid concentrations expose more active sites of polydopamine molecules to promote endothelial cell proliferation while retaining the intrinsic antithrombogenic function of hyaluronic acid to offer a potential application for vascular stents.

Cell-free protein synthesis andin situimmobilization of deGFP-MatB in polymer microgels for malonate-to-malonyl CoA conversion

In the present work, microgels were utilized as a cell-free reaction environment to produce a functional malonyl-CoA synthetase (deGFP-MatB) under geometry-controlled transcription and translation. Our approach combines the straight-forward optimization of overall protein yield of an E. coli-based cell-free protein synthesis (CFPS) system based on concentration screening of magnesium and potassium glutamate, DNA as well as polyethylene glycol (PEG), and its innovative usage in microgel-based production of a key enzyme of the polyketide synthesis pathway. After partial modification of the carboxyl groups of hyaluronic acid (HA) with 5′-methylfuran groups via 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM)-activation, these were further functionalized with dibenzocyclooctyne (DBCO) and nitrilotriacetic acid (NTA) groups by bio-orthogonal [4+2] Diels–Alder cycloaddition to yield a bifunctional macromer. After coupling the DBCO groups with azide-functionalized DNA, containing the genetic information for deGFP-MatB, via strain-promoted azide–alkyne cycloaddition (SPAAC), the DNA-/NTA-functionalized HA macromer was utilized as base material together with maleimide-functionalized PEG (PEG-mal2) as the crosslinker to form bifunctional microgels utilizing water-in-oil (W/O) microemulsions. As-formed microgels were incubated with nickel sulfate to activate the NTA groups and provide binding sites for deGFP-MatB, which contained six histidine residues (His-tag) for that purpose. The optimized CFPS mixture was loaded into the microgels to initiate the formation of deGFP-MatB, which was detected by a clear increase in fluorescence exclusively inside the microgel volume. Functionality of both, the bound and the decoupled enzyme was proven by reaction with malonate to yield malonyl CoA, as confirmed by a colorimetric assay.

Dual-functionalized hyaluronic acid as a facile modifier to prepare polyanionic collagen

Hyaluronic acid (HA) is a natural polysaccharide possesses outstanding physiological activities. In this work, HA was activated as a novel collagen modifier via the esterification reaction between N-hydroxysuccinimide (NHS) and the carboxyl groups of HA. Both of Fourier transform infrared spectroscopy (FTIR) and 1H- nuclear magnetic resonance (NMR) spectra indicated the successful synthesis of HA-NHS esters. As reflected by FTIR, circular dichroism (CD) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), collagens modified with HA-NHS ester maintained its intact triplex structure with larger molecular weight. The resultant polyanionic collagen displayed an excellent dissolubility in the neutral water to form a clear solution, due to the significantly lower isoelectric point values (3.8–4.4) compared with that of the native collagen (7.1). In addition, the thermal transition temperature of collagen was significantly increased (16 °C) after modifying with HA-NHS esters. Both of the aggregation morphology and rheological property exhibited high dependence on the NHS/COOH ratio of HA-NHS esters, as reflected by field-emission scanning electron microscopy (FESEM) and rheological test, respectively. The present study offered a novel dual-functional modifier based on the design of HA-NHS ester to obtain water-soluble collagen with desired thermal stability and rheological property, which will significantly widen the application range of collagen, especially in the fields of injectable biodegradable materials and cosmetics.

Formation and Characterization of Lactoferrin-Hyaluronic Acid Conjugates and Their Effects on the Storage Stability of Sesamol Emulsions.

The purpose of this study was to fabricate biopolymer conjugates from lactoferrin (LF) and hyaluronic acid (HA) and then to investigate their potential as emulsifiers for forming sesamol-loaded emulsions. Initially, LF-HA covalent conjugates were formed using the carbodiimide coupling method in aqueous solutions at pH = 4.5, and then the nature of the conjugates was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, and fluorescence spectroscopy. The results demonstrated the formation of an amide link between the amine groups of LF and the carboxyl groups of HA. Sesamol emulsions were prepared using the LF-HA conjugates as emulsifiers and their stability was determined. The conjugates improved both the physical and chemical stability of the emulsions during storage. Optimum stability of the emulsion was obtained at a LF-to-HA molar ratio of 2:1. Our results suggest that LF-HA conjugates may be effective emulsifiers for use in food stuffs and other applications.

Layer-by-layer nanoparticles co-loading gemcitabine and platinum (IV) prodrugs for synergistic combination therapy of lung cancer.

PurposeCisplatin plus gemcitabine (GEM) is a standard regimen for the first-line treatment of advanced non-small cell lung cancer. The aim of this study was to prepare biocompatible and biodegradable polymeric prodrugs and construct nanoparticles (NPs) with layer-by-layer (LbL) technique.MethodsPlatinum (Pt) (IV) complex with a carboxyl group was conjugated to the amino group of chitosan (CH), resulting in a CH-Pt conjugation with positive charge. GEM with amino group was conjugated to the carboxyl group of hyaluronic acid (HA), resulting in a HA-GEM conjugation with negative charge. Novel LbL NPs consisting of the CH-Pt core and the HA-GEM layer, named as HA-GEM/CH-Pt NPs, were constructed. The physicochemical properties of the HA-GEM/CH-Pt NPs were investigated. In vitro cytotoxicity against human non-small lung cancer cells (NCl-H460 cells) was investigated, and in vivo antitumor efficiency was evaluated on mice bearing NCl-H460 cells xenografts.ResultsHA-GEM/CH-Pt NPs have a size of about 187 nm, a zeta potential value of −21 mV and high drug encapsulation efficiency of 90%. The drug release of HA-GEM/CH-Pt NPs exhibited a sustained behavior. HA-GEM/CH-Pt NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against lung cancer animal model compared to the single-drug-loaded NPs and free drug solutions.ConclusionThe results demonstrated that the HA-GEM/CH-Pt NPs might be a promising system for the synergetic treatment of lung carcinoma.

Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer.

Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.

PH sensitive polymeric complex of cisplatin with hyaluronic acid exhibits tumor-targeted delivery and improved in vivo antitumor effect

Cisplatin (CDDP) is widely used anticancer drug for various solid tumors including lung cancer. However, its indiscriminate distribution causes serious adverse effects and limits its therapeutic effect. In this study, by using hyaluronic acid (HA) we synthesized a complex of CDDP (HA-CDDP), by utilizing ionic interaction between Pt2+ of CDDP with carboxyl group of HA. The mean HA-CDDP particle size was 208.5nm in PBS according to dynamic light scattering which was also confirmed by TEM, which could exert tumor-targeting property by enhanced permeability and retention (EPR) effect. The CDDP loading in this preparation was 13% (w/w), and release rate of free CDDP from the HA-CDDP complex at physiological pH (7.4) was ∼20%/day. However, in acidic pH the release was much faster, i.e., ∼95% of CDDP was released in 72h at pH 5.5. Moreover, HA-CDDP showed a 2.5-fold higher tumor accumulation than free CDDP whereas no increase of distribution was found in most normal tissues. In addition, because HA receptor CD44 is overexpressed in many tumor cells, we also observed CD44-based endocytosis of HA-CDDP in mouse lung carcinoma LCC cells. These findings together suggest that HA-CDDP may show tumor-selective cytotoxicity by taking advantage of EPR effect, weak acidic environment of tumor tissues (e.g., pH 6∼7), as well as CD44-based intracellular uptake. As expected, HA-CDDP exhibited much improved therapeutic effect than free CDDP in mouse LCC tumor model, whereas no apparent side effect was found. These findings may shed some light on the potential utility of HA for development of tumor-targeted polymeric CDDP drugs, which need further investigations.

Hyaluronic Acid Based Hydrogels Attenuate Inflammatory Receptors and Neurotrophins in Interleukin-1β Induced Inflammation Model of Nucleus Pulposus Cells.

Inflammation plays an important role in symptomatic intervertebral disc degeneration and is associated with the production of neurotrophins in sensitizing innervation into the disc. The use of high molecular weight (HMw) hyaluronic acid (HA) hydrogels offers a potential therapeutic biomaterial for nucleus pulposus (NP) regeneration as it exerts an anti-inflammatory effect and provides a microenvironment that is more suitable for NP. Therefore, it was hypothesized that cross-linked HMw HA hydrogels modulate the inflammatory receptor of IL-1R1, MyD88 and neurotrophin expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in an in vitro inflammation model of NP. HA cross-linking was optimized using various concentrations of 4-arm PEG-amine by determination of free carboxyl groups of HA and unreacted free amine groups of PEG-amine. The optimally cross-linked HA hydrogels were characterized for hydrolytic stability, enzymatic degradation and cytotoxicity on NP cells. The therapeutic effect of HA hydrogels was further investigated in IL-1β induced inflammation on NP cell cultures and the mechanism of HA by examining the expression of cell surface receptor of CD44. Hydrogel was optimally cross-linked at 75 mM PEG, stable in phosphate buffered saline, and showed greater than 40% resistance to enzymatic degradation. No cytotoxic effect of NP cells was observed in the presence of hydrogels for 1, 3, and 7 days. IL-1R1 and MyD88 were significantly suppressed. Additionally, NGF and BDNF mRNA were down-regulated after treatment with cross-linked HA hydrogel. Possible protective mechanism of HA is shown by high expression of CD44 receptor of NP cells after HA treatment in which suggest the binding of HA to CD44 receptor and prevent NP cells from further undergoing inflammation. These results indicate that optimally stabilized cross-linked HMw HA hydrogel has a therapeutic effect in response to inflammation-associated pain and becomes an ideal matrices hydrogel for NP regeneration.

Injectable photoreactive azidophenyl hyaluronic acid hydrogels for tissue augmentation

A photoreactive azidophenyl hyaluronic acid (Az-HA) derivative for tissue augmentation was prepared by direct amide bond formation between the carboxyl groups of HA and the amine groups of 4-azidoaniline. 4-Azidoaniline was introduced to the carboxyl group of hyaluronic acid that was activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The prepared Az-HA derivative was characterized by 1H NMR to measure the degree of modification. The Az-HA derivative was photo-cross-linked with varying UV irradiation times. Az-HA-20 hydrogels were formulated into injectable gels for soft tissue augmentation. The morphology, equilibrium swelling, rheological property, and in vitro degradation of hydrogels were examined. The cell cytotoxicity test of the Az-HA derivative was also examined. Az-HA-20 formed stronger hydrogels with higher storage modulus (Pa’) as UV irradiation time increased. Also, the in vitro degradation rate was lower as UV irradiation time increased. This study demonstrates that Az-HA-20 hydrogels have potential for use as injectable, biodegradable, and biocompatible hydrogels for tissue augmentation. Open image in new window

Adhesion of Marine Fouling Organisms on Hydrophilic and Amphiphilic Polysaccharides

Polysaccharides are a promising material for nonfouling surfaces because their chemical composition makes them highly hydrophilic and able to form water-storing hydrogels. Here we investigated the nonfouling properties of hyaluronic acid (HA) and chondroitin sulfate (CS) against marine fouling organisms. Additionally, the free carboxyl groups of HA and CS were postmodified with the hydrophobic trifluoroethylamine (TFEA) to block free carboxyl groups and render the surfaces amphiphilic. All coatings were tested with respect to their protein resistance and against settlement and adhesion of different marine fouling species. Both the settlement and adhesion strength of a marine bacterium (Cobetia marina), zoospores of the seaweed Ulva linza, and cells of a diatom (Navicula incerta) were reduced compared to glass control surfaces. In most cases, TFEA capping increased or maintained the performance of the HA coatings, whereas for the very well performing CS coatings the antifouling performance was reduced after capping.

Preparation of photoreactive azidophenyl hyaluronic acid derivative: Protein immobilization for medical applications

Photoreactive azidophenyl hyaluronic acid (Az-HA) derivative was synthesized to immobilize proteins such as epidermal growth factor (EGF) and bone morphogenetic protein (BMP). The photosensitizing group, 4-azidoaniline, was introduced to the carboxyl group of hyaluronic acid by a water soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). To characterize the synthesized Az-HA, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR) and ultraviolet/visible (UV/vis) absorbance spectroscopy were performed. We demonstrated protein immobilization by using fluorescein isothiocyanate conjugated albumin (FITCBSA) on Az-HA derivative surfaces that were patterned with micro scale. Cytotoxicity and relative cell proliferation tests of the Az-HA derivative were performed on an MG-63 human osteoblast cell line for biocompatibility. Open image in new window

Permanent hair dye-incorporated hyaluronic acid nanoparticles

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.