Hyaluronic Acid Layer Research Articles

Interactions between Lubricin and Hyaluronic Acid Synergistically Enhance Antiadhesive Properties.

Preventing the unwanted adsorption of proteins and cells at articular cartilage surfaces plays a critical role in maintaining healthy joints and avoiding degenerative diseases such as osteoarthritis. Immobilized at the surface of healthy articular cartilage is a thin, interfacial layer of macromolecules consisting mainly of hyaluronic acid (HA) and lubricin (LUB; a.k.a. PRG4) that is believed to form a co-adsorbed, composite film now known to exhibit synergistic tribological properties. Bioinspired by the composition of cartilage surfaces, composite layers of HA and LUB were grafted to Au surfaces and the antiadhesive properties were assessed using surface plasmon resonance and quartz crystal microbalance. A clear synergistic enhancement in antiadhesive properties was observed in the composite films relative to grafted HA and LUB layers alone. Atomic force microscopy (AFM) normal force measurements provide insight into the architecture of the HA/LUB composite layer and implicate a strong contribution of hydrophobic interactions in the binding of LUB end-domains directly to HA chains. These AFM force measurements indicate that the adhesion of LUB to HA is strong and indicate that the hydrophobic coupling of LUB to HA shields the hydrophobic domains in these molecules from interactions with other proteins or molecules.

Enzymatic Hydrolysis of Hyaluronic Layer before Drug Dosing

The local therapy is a particularly proper approach in treatment of cancer diseases, at which the drugs are highly toxic. Unfortunately, antitumor drugs diffusion is quite often limited by hyaluronic acid layers abundantly found in a cancer tissue. The undertaken approach assumed relaxation of hyaluronan layer by using a hydrolytic enzyme - hyaluronidase. The considered process corresponds to the heterogenic catalysis with substrate occurred as a layer and a catalyst in a native form. It was shown that enzyme concentration around 4 mg/L kept for 10 minutes in body fluid surrounding HA layers is enough to allow the drug to diffuse. Cyanocobalamin, as a model drug, was applied in diffusion processes testing. The possibility of hyaluronidase releasing in the place close to hyaluronic acid layers was also considered. Hydrogel carriers promoting fast release of hyaluronidase were characterized. The profile of releasing Hase from the tested carriers based on κ-carrageenan or sodium alginate with polyvinyl alcohol corresponded to Higuchi model. An expected rate value (the mass transport coefficient app. 4.0.10-7 m/s) was obtained for blends 0.5% κ-carrageenan, 4% polyvinyl alcohol and 0.5% sodium alginate, 6% polyvinyl alcohol.

A self-delivery system based on an amphiphilic proapoptotic peptide for tumor targeting therapy.

In recent decades, drug self-delivery systems (DSDSs) have appeared with extraordinary superiority for cancer therapy while realizing intracellular delivery without supererogatory drug carriers. Here, we have designed and programmed a novel self-delivery system to realize tumor targeting therapy. The amphiphilic proapoptotic peptide KLAKLAKKLAKLAKGCK(Fmoc)2 (KLA) was used to form a self-assembled structure (KD) by encapsulating the hydrophobic anticarcinogen doxorubicin (DOX). Then, tumor recognizing hyaluronic acid (HA) was coated on the surface of KD to obtain a tumor targeting self-delivery system (KDH). The protective layer of HA could protect the therapeutic agents from being inactivated during blood circulation, and further specifically recognize tumor cells by the CD44 receptor after KDH had located the tumor regions. Additionally, hyaluronidase (HAase) overexpressed in the endosome of tumor cells could degrade the protective layer of HA and accelerate the liberation of KLA and DOX. The proapoptotic peptide KLA had the ability to locate mitochondria and induce mitochondrial dysfunction; meanwhile the anticarcinogen DOX diffused to the nuclei to inhibit the growth of tumor cells. Both in vitro and in vivo studies identified that our self-delivery system KDH possessed precise tumor targeting, and exhibited fantastic antitumor efficacy as well as negligible side effects.

Impact of a Hyaluronic Acid-Grafted Layer on the Surface Properties of Model Silicone Hydrogel Contact Lenses

The introduction of high oxygen transmissibility silicone hydrogel lenses ameliorated hypoxia-related complications, making them the most prescribed type of contact lens (CL). Despite the progress made over the last 2 decades to improve their clinical performance, symptoms of ocular dryness and discomfort and a variety of adverse clinical events are still reported. Consequently, the rate of CL wear discontinuation has not been appreciably diminished by their introduction. Aiming to improve the interfacial interactions of silicone hydrogel CLs with the ocular surface, a biomimetic layer of hydrophilic glycosaminoglycan hyaluronic acid (HA) (100 kDa) was covalently attached to the surface of model poly(2-hydroxyethyl methacrylate- co-3-methacryloxypropyl-tris-(trimethylsiloxy)silane) (pHEMA- co-TRIS) silicone hydrogel materials via UV-induced thiol-ene "click" chemistry. The surface structural changes after each modification step were studied by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy (XPS). Successful grafting of a homogeneous HA layer to the surface of the model silicone hydrogels was confirmed by the consistent appearance of N (1s) and the significant decrease of the Si (2p) peaks, as determined by low-resolution angle-resolved XPS. The HA-grafted surfaces demonstrated reduced contact angles, dehydration rate, and nonspecific deposition of lysozyme and albumin, while maintaining their optical transparency (>90%). In vitro studies demonstrated that the HA-grafted pHEMA- co-TRIS materials did not show any toxicity to human corneal epithelial cells. These results suggest that surface immobilization of HA via thiol-ene "click" chemistry can be used as a promising surface treatment for silicone hydrogel CLs.

Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics.

In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy.

Induction of zonal-specific cellular morphology and matrix synthesis for biomimetic cartilage regeneration using hybrid scaffolds.

Cartilage is anisotropic in nature and organized into distinct zones. Our goal was to develop zonal-specific three-dimensional hybrid scaffolds which could induce the generation of zonal-specific cellular morphology and extracellular matrix (ECM) composition. The superficial and middle zones comprised two layers of hyaluronic acid (HA) hydrogel which enveloped specifically orientated or randomly arranged polylactic acid nanofibre meshes. The deep zone comprised a HA hydrogel with multiple vertical channels. Primary bovine chondrocytes were seeded into the individual zonal scaffolds, cultured for 14 days and then the ECM was analysed. The aligned nanofibre mesh used in the superficial zone induced an elongated cell morphology, lower glycosaminoglycan (GAG) and collagen II production, and higher cell proliferation and collagen I production than the cells in the middle zone scaffold. Within the middle zone scaffold, which comprised a randomly orientated nanofibre mesh, the cells were clustered and expressed more collagen II. The deep zone scaffold induced the highest GAG production, the lowest cell proliferation and the lowest collagen I expression of the three zones. Assembling the three zones and stabilizing the arrangement with a HA hydrogel generated aligned, randomly aggregated and columnar cells in the superficial, middle and deep zones. This study presents a method to induce zonal-specific chondrocyte morphology and ECM production.

Ionic coupling of hyaluronic acid with ethyl N-lauroyl l-arginate (LAE): Structure, properties and biocide activity of complexes

Ethyl αN-lauroyl l-arginate hydrochloride (LAE) was coupled with hyaluronic acid (HyA) to form ionic complexes with LAE to HyA ratios of 1:1 and 1:2. The complexes were extensively characterized by FTIR and NMR spectroscopies and their thermal properties evaluated by thermogravimetry and calorimetry. Thin films prepared from these complexes by casting displayed a smectic-like structure based on an ordered arrangement of LAE and HyA layers with a nanometric periodicity of 3.8–3.9 nm. Films immersed in water at pH 7.4 and 5.5 dissociated to deliver free LAE to the environment and reaching the equilibrium in few hours. The biocide activity of these films against both Gram-positive and Gram-negative bacteria was preliminary assessed by the liquid medium method, and shown to be notable in both cases. The antibacterial property of the complexes was found to increase with the content of LAE and to be particularly efficient against Gram-negative S. enterica bacteria.

Synthesis and Characterization of Functional Nanofilm-Coated Live Immune Cells

Layer-by-layer (LbL) assembly techniques have been extensively studied in cell biology because of their simplicity of preparation and versatility. The applications of the LbL platform technology using polysaccharides, silicon, and graphene have been investigated. However, the applications of the above-mentioned technology using living cells remain to be fully understood. This study demonstrates a living cell-based LbL platform using various types of living cells. In addition, it confirms that the surplus charge on the outer surface of the coated cells can be used to bind the target protein. We develop a living cell-based LbL platform technology by stacking layers of hyaluronic acid (HA) and poly-l-lysine (PLL). The HA/PLL stacking results in three bilayers with a thickness of 4 ± 1 nm on the cell surface. Furthermore, the multilayer nanofilms on the cells are completely degraded after 3 days of the application of the LbL method. We also evaluate and visualize three bilayers of the nanofilm on adherent (AML-12 cells)-, nonadherent (trypsin-treated AML-12 cells)-, and circulation type [peripheral blood mononuclear cells (PBMCs)] cells by analyzing the zeta potential, cell viability, and imaging via scanning electron microscopy and confocal microscopy. Finally, we study the cytotoxicity of the nanofilm and characteristic functions of the immune cells after the nanofilm coating. The multilayer nanofilms are not acutely cytotoxic and did not inhibit the immune response of the PBMCs against stimulant. We conclude that a two bilayer nanofilm would be ideal for further study in any cell type. The living cell-based LbL platform is expected to be useful for a variety of applications in cell biology.

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

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 wear.

Elaboration of antibacterial plastic surfaces by a combination of antiadhesive and biocidal coatings of natural products

Antibacterial polyolefins surfaces, combining biocidal and antiadhesive properties, were elaborated by a covalent grafting of antimicrobial peptides (AMPs), able to kill adherent bacteria, on a pre-immobilized hyaluronic acid (HA) layer, able to repel the micro-organisms. Different HA activation rate for its immobilization, were used to change HA layer morphology and number of residual free carboxylic acid functions for AMPs grafting. Based on adhesion tests on Staphylococcus epidermidis and microscopy fluorescent observations, the presence of the two combined properties was shown to be depended on the HA activation rate. Thus, the best addition effect was observed for an AMP grafting on a surface based on a high HA activation, data pointing out a decrease of the bacterial adhesion up to 99.8% and a perturbation of the bacterial membrane integrity of adhered bacteria. On the contrary, a decrease of the antibacterial activity was observed for an AMP grafting on a surface based on a low HA activation.

Preparation of an Arg-Glu-Asp-Val Peptide Density Gradient on Hyaluronic Acid-Coated Poly(ε-caprolactone) Film and Its Influence on the Selective Adhesion and Directional Migration of Endothelial Cells

Selective adhesion and migration of endothelial cells (ECs) over smooth muscle cells (SMCs) is very important in the rapid endothelialization of blood-contacting implants to prevent vascular restenosis. In this study, a uniform cell-resistant layer of methacrylate-functionalized hyaluronic acid (HA) was first immobilized on a poly(ε-caprolactone) (PCL) film via polydopamine coupling. Then, a density gradient of thiol-functionalized Arg-Glu-Asp-Val (REDV) peptide was prepared on the HA layer via thiol-ene click chemistry and the continuous injection method. The REDV gradient selectively enhanced EC adhesion and preferential directional migration toward the region of higher REDV density, reaching 86% directionality in the middle of the gradient. The migration rate of ECs was also significantly enhanced twofold compared with that on tissue culture polystyrene (TCPS). In contrast, the gradient significantly weakened the adhesion of SMCs to 25% of that on TCPS but had no obvious impact on the migration rate and directionality. Successful modulation of the selective adhesion and directional migration of ECs over SMCs on biodegradable polymers serves as an important step toward practical applications for guided tissue regeneration.

Novel Technique for Isolating Human Bone Marrow Stem Cells Using Hyaluronic Acid Hydrogel.

Centrifugation based on density gradients is a general methodology for isolating human bone marrow (hBM)-derived mesenchymal stem cells (hBMSCs). The mononuclear cell (MNC) layer can be obtained using a density gradient solution in the conventional protocol, but it is not suitable for direct transplantation due to the possible toxicity of this solution. The results obtained are also influenced by the skill level when applying the technique, which involves time-consuming processes. We have developed a novel protocol for isolating hBMSCs using hyaluronic acid (HA), which is the most widely used injectable biomaterial in clinical settings and a major component of the extracellular matrix. Laying hBM over the HA and then applying centrifugation yielded three separate layers, with the HA layer, including MNCs being the most superficial one. Increasing the volume of HA and/or its crosslinking rate enhanced the yield of MNCs from hBM, and the cell yield was also significantly higher for a lower centrifugal acceleration (530 g) than for a higher one (1500 g). Isolated hBMSCs by HA exhibited similar biological characteristics such as in terms of their proliferation rate, fibroblast-like morphology, cell-cycle status, immunophenotype, and multipotency. The use of either type of hBMSC confirmed the regenerative potential of bone and bone marrow-like tissue in ectopic transplantation models. This is the first report of a novel protocol for isolating hBMSCs that utilize HA. We suggest that this novel isolation technique can be used for the direct application of autogenous MSCs with advantages of being less time-consuming and involving steps that are easier to perform.

Study on biomimetic mineralization of lipopolysaccharide-amine nanopolymersomes/hyaluronic acid polyelectrolyte films on titanium surface

To explore biomimetic mineralization of polyelectrolyte multilayer films (PEM) of gene-loaded lipopolysaccharide-amine nanopolymersomes/hyaluronic acid self assembled on titanium surface. Via lay-by-layer self assembly technology, PEM were constructed on titanium or quartz surface using bone morphogenetic protein-2(BMP-2) plasmid-loaded lipopolysaccharide-amine nanopolymersomes(pLNP) as a polycation, and hyaluronic acid(HA) as a polyanion. The constructed PEM were defined as substrate-pLNP-(HA-pLNP)n, where a successive deposition of HA and pLNP on substrate surface was defined as one assembly cycle, and n was the cycle number. Biomimetic mineralization on surfaces of Ti-pLNP-(HA-pLNP)4(Group A, with outermost layer of pLNP), Ti-pLNP-(HA-pLNP)4.5(Group B, with outermost layer of HA), blank control(polished titanium, Ti) and alkaline-heat treated titanium(Ti-OH) were investigated. The biomimetic mineralization was analyzed by observing the topography under field-emisssion electron microscopy(FE-SEM), characterizing the surface chemical structure and components via X-ray diffractometer(XRD) and X-ray energy disperse spectroscopy(EDS). For experiment groups, XRD analysis showed that the diffraction peak of hydroxyapatite appeared, and its intensity was higher than that for Ti group. FE-SEM images showed that its surface was homogeneously covered by discrete agglomerate of big particles. EDS spectra showed that the percentage of Ca and P were 77.24% and 64.23%, and these were much higher than those in Ti group. The surface of Ti-pLNP-(HA-pLNP)n is favorable for in vitro biomimetic mineralization.

Control of particle uptake kinetics from particulate mesoporous silica films by cells through covalent linking of particles to the substrate - towards sequential drug delivery for tissue engineering applications.

A sequential release of biological cues is of high interest in tissue engineering applications, as both the proliferation and the differentiation of stem cells can be drugged. In previous studies we have shown that particulate films of mesoporous silica particles can be successfully applied for influencing stem cell fates through intracellular drug delivery after particle internalisation by the cells. In this study, we develop this concept towards an enhanced control of the particle uptake kinetics through either adsorption or covalent linking of the mesoporous silica particles to the substrate. Microscopy glass slides were initially functionalized by an aminosilane to which a thin layer of hyaluronic acid was covalently attached through an amide bond. A sub-monolayer of amino-functionalized mesoporous silica nanoparticles with a diameter of 400 nm were then adsorbed to the hyaluronic acid-functionalized surface by adsorption under high-shear conditions. Subsequently, the adsorbed particles were covalently linked to the hyaluronic acid through an amide bond. Corresponding films without the covalent coupling step were used as the control. Muscle stem cells attach and proliferate nicely on all films, and do internalize particles in all cases. However, the kinetics of particle internalization was clearly delayed for the covalently attached particles in comparison to physisorbed particles. Thus, the results imply that tuning of the particle-substrate interactions through linking chemistries is a promising means of achieving sequential particle-mediated drug release from films and that corresponding chemistries should also be applicable for 3D scaffold systems.

Bioinspired lubricating films of cellulose nanofibrils and hyaluronic acid

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

Protein, cell and bacterial response to atmospheric pressure plasma grafted hyaluronic acid on poly(methylmethacrylate).

Hyaluronic acid (HA) has been immobilised on poly(methyl methacrylate) (PMMA) surfaces using a novel dielectric barrier discharge (DBD) plasma process for the purposes of repelling protein, cellular and bacterial adhesion in the context of improving the performance of ophthalmic devices. Grafting was achieved by the following steps: (1) treatment of the PMMA with a DBD plasma operating at atmospheric pressure, (2) amine functionalisation of the activated polymer surface by exposure to a 3-aminopropyltrimethoxysilane (APTMS) linker molecule and (3) reaction of HA with the surface bound amine. The mechanism and effectiveness of the grafting process was verified by surface analysis. XPS data indicates that the APTMS linker molecule binds to PMMA via the Si-O chemistry and has the required pendant amine moiety. The carboxylic acid moiety on HA then binds with this -NH2 group via standard carbodiimide chemistry. ToF-SIMS confirms the presence of a coherent HA layer the microstructure of which is verified by AFM. The plasma grafted HA coating surfaces showed a pronounced decrease in protein and cellular adhesion when tested with bovine serum albumin and human corneal epithelial cells, respectively. The ability of these coatings to resist bacterial adhesion was established using Staphylococcus aureus NTC8325. Interestingly, the coatings did not repel bacterial adhesion, indicating that the mechanism of adhesion of bacterial cells is different to that for the surface interactions of mammalian cells. It is proposed that this difference is a consequence of the specific HA conformation that occurs under the conditions employed here. Hence, it is apparent that the microstructure/architecture of the HA coatings is an important factor in fabricating surfaces intended to repel proteins, mammalian and bacterial cells.

Surface Modification of Ultra-High Molecular Weight Polyethylene with Crosslinked Hyaluronic Acid and its Antiwear Performance

The surface of high-pressure crystallized ultra-high molecular weight polyethylene (UHMWPE) was modified for application as an artificial cartilage material. A UHMWPE surface pretreated by a series of processes, including treatment with O2-plasma and ethylenediamine solution, was coated with hyaluronic acid (HA). After that, adipic acid dihydrazide (AAD) was added to partially crosslink the HA coating in order to enhance its durability. The modified samples were verified by water contact angle measurement and Fourier transform infrared spectrometry. Both HA layers, original and crosslinked, were also quantitatively evaluated by carbohydrate chemistry assay according to the absorbance of the incident light. The tribological performance of the samples was evaluated by a pin-on-disk test rig lubricated by normal saline under an average pressure of 18 MPa and at a sliding speed of 0.03 m/s for 45 h. The wear resistance of the HA-coated UHMWPE specimens promoted by the crosslink process was superior to that of the original HA-coated sample, and that resistance was maintained after immersion in saline solution for one month.

Adsorption of hyaluronic acid on solid supports: Role of pH and surface chemistry in thin film self-assembly

Owing to its biocompatibility, resistance to biofouling, and desirable physicochemical and biological properties, hyaluronic acid (HA) has been widely used to modify the surface of various materials. The role of various physicochemical factors in HA adsorption remains, however, to be clarified. Herein, we employed quartz crystal microbalance with dissipation (QCM-D) in order to investigate HA adsorption at different pH conditions onto three substrates—silicon oxide, amine-terminated self-assembled monolayer (SAM) on gold, and carboxylic acid-terminated SAM on gold. The QCM-D experiments indicated specific pH conditions where either strong or weak HA adsorption occurs. The morphology of the adsorbed HA layers was investigated by atomic force microscopy (AFM), and we identified that strong HA adsorption produced a complete, homogenous and smooth HA layer, while weak HA adsorption resulted in rough and inhomogeneous HA layers. The observed specifics of the kinetics of HA adsorption, including a short initial linear phase and subsequent long non-linear phase, were described by using a mean-field kinetic model taking HA diffusion limitations and reconfiguration in the adsorbed state into account. The findings extend the physicochemical background of design strategies for improving the use of passive HA adsorption for surface modification applications.

Grafting hyaluronic acid onto gold surface to achieve low protein fouling in surface plasmon resonance biosensors.

Antifouling surfaces capable of reducing nonspecific protein adsorption from natural complex media are highly desirable in surface plasmon resonance (SPR) biosensors. A new protein-resistant surface made through the chemical grafting of easily available hyaluronic acid (HA) onto gold (Au) substrate demonstrates excellent antifouling performance against protein adsorption. AFM images showed the uniform HA layer with a thickness of ∼10.5 nm on the Au surface. The water contact angles of Au surfaces decreased from 103° to 12° with the covalent attachment of a carboxylated HA matrix, indicating its high hydrophilicity mainly resulted from carboxyl and amide groups in the HA chains. Using SPR spectroscopy to investigate nonspecific adsorption from single protein solutions (bovine serum albumin (BSA), lysozyme) and complex media (soybean milk, cow milk, orange juice) to an HA matrix, it was found that ultralow or low protein adsorptions of 0.6-16.1 ng/cm(2) (e.g., soybean milk: 0.6 ng/cm(2)) were achieved on HA-Au surfaces. Moreover, anti-BSA was chosen as a model recognition molecule to characterize the immobilization capacity and the antifouling performance of anti-BSA/HA surfaces. The results showed that anti-BSA/HA sensor surfaces have a high anti-BSA loading of 780 ng/cm(2), together with achieving the ultralow (<3 ng/cm(2) for lysozyme and soybean milk) or low (<17 ng/cm(2) for cow milk and 10% blood serum) protein adsorptions. Additionally, the sensor chips also exhibited a high sensitivity to BSA over a wide range of concentrations from 15 to 700 nM. Our results demonstrate a promising antifouling surface using extremely hydrophilic HA as matrix to resist nonspecific adsorption from complex media in SPR biosensors.

Reducing the Foreign Body Reaction by Surface Modification with Collagen/Hyaluronic Acid Multilayered Films

Biological response against foreign implants often leads to encapsulation, possibly resulting in malfunction of implants devices. The aim of this study was to reduce the foreign body reaction by surface modification of biomaterials through layer-by-layer deposition of type I collagen (COL)/hyaluronic acid (HA) multilayer films. Polydimethylsiloxane (PDMS) samples were coated with alternative COL and HA layers with different layers. We found that the in vitro adhesion, proliferation, and activation of macrophage-like cells were greatly decreased by COL/HA multilayered deposition. The PDMS samples modified with 20 bilayers of COL/HA were implanted in rats for 3 weeks, and the thickness of encapsulation surrounding the samples was decreased by 29–57% compared to the control unmodified PDMS. This study demonstrates the potential of COL/HA multilayer films to reduce foreign body reaction.