Antifouling Hydrogel Research Articles

Novel Balanced Charged Alginate/PEI Polyelectrolyte Hydrogel that Resists Foreign-Body Reaction.

Foreign-body reaction (FBR) has been a long-term obstacle for implantable biomedical devices and materials, especially to those that require mass/signal transport between the implants and the body. However, currently, very limited biomaterials can mitigate FBR. In this work, we develop a balanced charged polyelectrolyte hydrogel that can efficiently resist FBR and collagenous capsule formation in a mouse model. Using this new strategy, we can easily tune the antifouling properties of the polyelectrolyte hydrogels by changing the ratio of negatively charged alginate and positively charged poly(ethylene imine). We find that at the optimum ratio where the net charge of hydrogel is neutral, the adhesion of proteins, cells, bacteria, and fresh blood on its surface can be significantly inhibited, indicating its excellent antifouling properties. In vivo studies show that after being implanted subcutaneously, this balanced charged hydrogel can prevent the capsule formation for at least 3 months. Furthermore, immunofluorescent staining results indicate that this balanced charged hydrogel elicits negligible inflammation, significantly reducing macrophage migration to the tissue-implant interface. This flexible and versatile approach holds a great promise for designing a wide spread of new antifouling hydrogels and using as immunoisolation materials for biomedical applications.

Water recycling efficacies of extremely hygroscopic, antifouling hydrogels.

Water harvesting, reusable, and antifouling hydrogels have found various applications in the fields of nanotechnology, biomedicine, food production and agriculture. These water-releasing materials are generally comprised of hygroscopic natural polymers, such as alginate blended with ionic salts or thermo-responsive moieties, to aid the release of water from a network of hydrogels. In this report, we propose a simple strategy to develop novel, synthetic, hygroscopic hydrogels (in the absence of ionic salts or thermo-responsive moieties), capable of absorbing copious amount of water and allow the facile release of water at ambient temperatures, as a function of crosslinking density of the polymer chains. The first step in the development of hygroscopic hydrogels is the development of hygroscopic vitamin B5 analogous or pantothenic acid analogous monomer (B5AMA), by ring opening chemistry. The hygroscopic hydrogels are then prepared from B5AMA monomer at different cross-linker densities by free radical polymerization approach and are evaluated for their antifouling properties and for their water absorbing and release efficacies, as a function of temperature. The release of significant amount of water by B5AMA hydrogels at physiological temperature (37 °C), their repeated water absorption and desorption behavior and excellent antifouling properties, suggest their potential usage as water harvesting materials in arid regions.

Cross-linked antifouling polysaccharide hydrogel coating as extracellular matrix mimics for wound healing.

Conventional wound dressings cannot provide an appropriate environment for tissue repair and regeneration and easily adhere to wounds causing damage to the new epithelial tissues, which leads to bleeding. Herein, a new antifouling hydrogel based on a natural polysaccharide was developed for wound healing. The biocompatible hydrogel with an ideal three-dimensional network composited of chitosan and dextran was synthesized by the Michael addition reaction. The hydrogel showed good swelling and cytocompatibility against NIH3T3. Moreover, the antifouling hydrogel was obtained by adjusting the proportion of positive and negative charges of chitosan and dextran. Antifouling hydrogels overcoming the deficiency of traditional wound dressings could inhibit bacterial and cellular adhesion effectively and also be applied as a carrier for protein delivery. After the wound was treated by bFGF-loaded hydrogels, significantly greater wound contraction was observed, which demonstrated their superior healing activity to promote fibroblast migration, granulation tissue formation and angiogenesis by up-regulation of VEGF and PCNA expression. These results showed that the obtained antifouling hydrogel may be a promising therapeutic strategy for managing diabetic ulcers.

Macro-initiator mediated surface selective functionalization of ultrafiltration membranes with anti-fouling hydrogel layers applicable to ready-to-use capillary membrane modules

A new process for surface selective graft modification of ultrafiltration (UF) membranes with protective hydrogel layers was developed. The process uses a random copolymer of n-butylmethacrylate and N,N-dimethylaminoethylmethacrylate as a redox co-initiator (“macro-initiator”). Due to its molecular weight, the macro-initiator is completely rejected by the used Multibore® polyethersulfone UF membranes. Zwitterionic [3-(methacryloylamino)propyl]dimethyl(3-sulfopropyl) ammonium hydroxide and bifunctional N,N′-methylenebis(acrylamide) were used as monomers for “macro-initiator”-mediated, surface selective cross-linking polymerization toward anti-fouling hydrogel layers. The functionalization comprises two main steps; i) adsorption of the macro-initiator to the barrier layer surface of the membrane, e.g. during a short ultrafiltration; ii) grafting of the hydrogel layer after bringing the membrane in contact with a solution containing monomer(s) and a dissolved initiator (here ammonium persulfate) which is complementary to the co-initiator for a predetermined reaction time at room temperature. Hydrogel-grafted flat sheet and capillary UF membranes showed dextran sieving curves shifted to lower molecular weight values, increased total organic carbon rejection and improved anti-fouling behaviour in filtration tests with flower soil extract as model foulant. Furthermore, stability tests with sodium hydroxide and hydrogen peroxide solutions showed good chemical stability of graft-functionalized membranes. The obtained results are very promising for future applications, since the presented technique can be applied in ready-to-use membrane modules and capillary membranes easily.

Detecting Surface Hydration of Poly(2-hydroxyethyl methacrylate) in Solution in situ

Understanding the interfacial molecular structures of antifouling polymers in solutions is extremely important in research and applications related to chemistry, biology, and medicine. However, it is generally challenging to probe such buried solid/liquid interfaces in situ. We herein report a molecular-level study on detecting the interfacial molecular structures of an antifouling hydrogel material, poly(2-hydroxyethyl methacrylate) (PHEMA), in contact with water and bovine serum albumin (BSA) solution in situ using sum frequency generation (SFG) vibrational spectroscopy. To compare to and validate our in situ experiments, molecular-level structures of the substrate/PHEMA interface before and after water exposure were also detected. The detected strong O–H vibrational signals from water and hydroxyethyl and carbonyl vibrational signals from PHEMA prove that the PHEMA surface hydration was attributed to the interaction between water and PHEMA side hydrophilic groups. SFG experimental results verify that t...

Fabrication of Robust Hydrogel Coatings on Polydimethylsiloxane Substrates Using Micropillar Anchor Structures with Chemical Surface Modification

A durable hydrophilic and protein-resistant surface of polydimethylsiloxane (PDMS) based devices is desirable in many biomedical applications such as implantable and microfluidic devices. This paper describes a stable antifouling hydrogel coating on PDMS surfaces. The coating method combines chemical modification and surface microstructure fabrication of PDMS substrates. Three-(trimethoxysilyl)propyl methacrylates containing C═C groups were used to modify PDMS surfaces with micropillar array structures fabricated by a replica molding method. The micropillar structures increase the surface area of PDMS surfaces, which facilitates secure bonding with a hydrogel coating compared to flat PMDS surfaces. The adhesion properties of the hydrogel coating on PDMS substrates were characterized using bending, stretching and water immersion tests. Long-term hydrophilic stability (maintaining a contact angle of 55° for a month) and a low protein adsorption property (35 ng/cm(2) of adsorbed BSA-FITC) of the hydrogel coated PDMS were demonstrated. This coating method is suitable for PDMS modification with most crosslinkable polymers containing C═C groups, which can be useful for improving the anti-biofouling performance of PDMS-based biomedical microdevices.

Bio-inspired self-cleaning PAAS hydrogel released coating for marine antifouling

In this paper, an antifouling hydrogel coating of slippery hydrogel-released hydrous surface (SHRHS) with the self-cleaning ability of oil-resistance and self-regeneration characters was designed. A physical blending method of loading Sodium polyacrylate (PAAS) powder into the organic silicon resin was employed to prepare the SHRHS coating. The oil-resistance of the intact and scratch SHRHS coatings was performed by time-sequence images of washing dyed beef tallow stain away. The results showed that the SHRHS coating has the greater ability of stain removal. The concentration of Na+ ions released from PAAS hydrogel on the surface of the SHRHS coating was investigated by ion chromatograph (IC). The results revealed that the coating had the ability of self-regeneration by PAAS hydrogel continuously peeling. The biomass of two marine microalgae species, Nitzschia closterium f. minutissima and Navicula climacospheniae Booth attached on the SHRHS was investigated using UV–Visible Spectrophotometer (UV) and Scanning electron microscopy (SEM). The results showed that the microalgaes attached a significantly lower numbers on the SHRHS in comparison with the organic silicon coating. In order to confirm the antifouling ability of the SHRHS coating, the field trials were carried out for 12weeks. It showed that the SHRHS may provide an effective attachment resistance to reduce biofouling.

In Vivo Investigations on Anti-Fouling Hydrogel Coatings

In Vivo Investigations on Anti-Fouling Hydrogel Coatings

Enhancement of Surface Graft Density of MPEG on Alginate/Chitosan Hydrogel Microcapsules for Protein Repellency

Alginate/chitosan/alginate (ACA) hydrogel microcapsules were modified with methoxy poly(ethylene glycol) (MPEG) to improve protein repellency and biocompatibility. Increased MPEG surface graft density (n(S)) on hydrogel microcapsules was achieved by controlling the grafting parameters including the buffer layer substrate, membrane thickness, and grafting method. X-ray photoelectron spectroscopy (XPS) model was employed to quantitatively analyze n(S) on this three-dimensional (3D) hydrogel network structure. Our results indicated that neutralizing with alginate, increasing membrane thickness, and in situ covalent grafting could increase n(S) effectively. ACAC(PEG) was more promising than ACC(PEG) in protein repellency because alginate supplied more -COO(-) negative binding sites and prevented MPEG from diffusing. The n(S) increased with membrane thickness, showing better protein repellency. Moreover, the in situ covalent grafting provided an effective way to enhance n(S), and 1.00 ± 0.03 chains/nm(2) was achieved, exhibiting almost complete immunity to protein adsorption. This antifouling hydrogel biomaterial is expected to be useful in transplantation in vivo.

Robust Method for High-Throughput Surface Patterning of Deformable Substrates

We describe a simple and robust method for high-throughput surface patterning of deformable substrates such as silicone rubber films covered with a thin layer of protein and cell antifouling hydrogel (PLL-g-PEG). The irradiation with deep UV (<200 nm) of PLL-g-PEG-coated rubber substrates through a synthetic quartz photomask created micropatterns over a large area of the substrate. Incubation with proteins resulted in stable patterns with high feature resolution. RPE1 cells seeded on fibronectin patterns were constrained for days even after stretching. We also propose the crossbow feature as an interesting example allowing the stretching of normalized stress fibers.

In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings

Anti-fouling hydrogel coatings, copolymers of 2-hydroxyethyl methacrylate, 1-vinyl-2-pyrrolidinone, and polyethylene glycol, were investigated for the purpose of improving biosensor biocompatibility. These coatings were modified to incorporate poly(lactide- co-glycolide) (PLGA) microspheres in order to release dexamethasone (DX) and/or vascular endothelial growth factor (VEGF). DX and VEGF release kinetics from microspheres, hydrogels, and microspheres embedded in hydrogels were determined in 2-week and 1-month studies. Overall, monolithic, non-degradable hydrogel drug release had an initial burst followed by release at a significantly lower amount. Microsphere drug release kinetics exhibited an initial burst followed by sustained release for 1 month. Embedding microspheres in hydrogels resulted in attenuated drug delivery. VEGF release from embedded microspheres, 1.1±0.3 ng, was negligible compared to release from hydrogels, 197±33 ng. After the initial burst from DX-loaded hydrogels, DX release from embedded microspheres was similar to that of hydrogels. The total DX release from hydrogels, 155±35 μg, was greater than that of embedded microspheres, 60±6 μg. From this study, hydrogel sensor coatings should be prepared incorporating VEGF in the hydrogel and DX either in the hydrogel or in DX microspheres embedded in the hydrogel.