Reduced Protein Adsorption Research Articles

Thrombogenic and Inflammatory Reactions to Biomaterials in Medical Devices.

Blood-contacting medical devices of different biomaterials are often used to treat various cardiovascular diseases. Thrombus formation is a common cause of failure of cardiovascular devices. Currently, there are no clinically available biomaterials that can totally inhibit thrombosis under the more challenging environments (e.g., low flow in the venous system). Although some biomaterials reduce protein adsorption or cell adhesion, the issue of biomaterial associated with thrombosis and inflammation still exists. To better understand how to develop more thrombosis-resistant medical devices, it is essential to understand the biology and mechano-transduction of thrombus nucleation and progression. In this review, we will compare the mechanisms of thrombus development and progression in the arterial and venous systems. We will address various aspects of thrombosis, starting with biology of thrombosis, mathematical modeling to integrate the mechanism of thrombosis, and thrombus formation on medical devices. Prevention of these problems requires a multifaceted approach that involves more effective and safer thrombolytic agents but more importantly the development of novel thrombosis-resistant biomaterials mimicking the biological characteristics of the endothelium and extracellular matrix tissues that also ameliorate the development and the progression of chronic inflammation as part of the processes associated with the detrimental generation of late thrombosis and neo-atherosclerosis. Until such developments occur, engineers and clinicians must work together to develop devices that require minimal anticoagulants and thrombolytics to mitigate thrombosis and inflammation without causing serious bleeding side effects.

Thromboresistance of Silicones Modified with PEO-Silane Amphiphiles.

The antifouling properties of poly(ethylene oxide) (PEO)-silane amphiphiles as surface-modifying additives (SMAs) in a condensation cure silicone have been previously demonstrated against simple protein solutions. Comprising an oligo(dimethylsiloxane) tether (m = 13 or 30) and PEO segment (n = 8), sustained protein resistance was achieved even in the absence of a cross-linkable triethoxysilane group, particularly when comprising the longer tether. To probe their potential for thromboresistance, PEO-silane amphiphile SMAs were used to bulk-modify silicones and evaluated for adhesion resistance against whole human blood under both static and dynamic conditions. Both a cross-linkable (XL diblock, m = 13) and a non-cross-linkable (Diblock, m = 30) SMA were evaluated at various concentrations (5-50 μmol SMA/g silicone) in a condensation cure silicone. Under static conditions, silicones modified with either SMA at concentrations of 10 μmol/g or greater were effective in reducing adhesion of human fibrinogen and platelets. Dynamic testing further showed that modified silicones were able to reduce protein adsorption and thrombus formation. This occurred at 5 and 10 μmol/g for silicones modified with XL diblock, m = 13 and Diblock, m = 30 SMAs, respectively. Combined, these results indicate the effectiveness of PEO-silane amphiphiles as SMAs in silicone for improved thromboresistance.

Cytocompatible and non-fouling zwitterionic hyaluronic acid-based hydrogels using thiol-ene “click” chemistry for cell encapsulation

In this work, a facile click reaction strategy is employed to form hydrogels in situ with cytocompatibility, biodegradability, self-healing property and resistance to protein. The thiol-functionalized zwitterionic carboxybetaine methacrylate copolymer, which take part as a cross-linker in the “thiol-ene” click reaction with the methacrylated hyaluronic acid. The hydrogels are obtained under the physiological condition without the presence of any copper catalyst and UV light. The hydrogel consisting of zwitterionic component shows an obvious reduction in protein adsorption and cell adhesion and avoid non-targeted factor interference in the biological experiments. The hydrogels also demonstrate adjustable degradation behavior. Human mesenchymal stem cells (hMSCs) are easily encapsulated into the hydrogels and remains metabolically active, indicating the excellent biocompatibility of the hydrogels. Additionally, the result of the cytokine secretion assays (IL-6 and TNF-α) has shown that this clickable hydrogel can serve to suppress inflammatory reactions and is beneficial for in vivo applications. Based on the above results, this clickable hydrogel with excellent performance can be an amenable platform for 3D cell encapsulation.

Covalent Mucin Coatings Form Stable Anti‐Biofouling Layers on a Broad Range of Medical Polymer Materials

AbstractApproximately 10% of all hospital patients contract infections from temporary clinical implants such as urinal and vascular catheters or tracheal tubes. The ensuing complications reach from patient inconvenience and tissue inflammation to severe, life threatening complications such as pneumonia or bacteremia. All these device‐associated nosocomial infections have the same origin: biofouling, i.e., the unwanted deposition of proteins, bacteria, and cells onto the device. To date, most strategies to overcome these problems are device specific, which results in high development efforts and costs. Here, it is demonstrated how one and the same coupling mechanism can be used to create a covalent antifouling coating employing mucin glycoproteins on multiple materials: with this method, a stable mucin layer can be generated on a broad range of polymer materials which are frequently used in medical engineering. It is shown that the mucin coating exhibits excellent stability against mechanical, thermal, and chemical challenges and reduces protein adsorption as well as prokaryotic and eukaryotic cell adhesion. Thus, the coating mechanism described here introduces a promising strategy to overcome biofouling issues on a broad range of medical devices.

Controlled radical polymerization of hydrophilic and zwitterionic brush-like polymers from silk fibroin surfaces.

Bombyx mori silk fibroin is a fibrous protein whose tunable properties and biocompatibility have resulted in its utility in a wide-variety of applications, including as drug delivery vehicles, wound dressings, and tissue engineering scaffolds. Control of protein and cell attachment is vital to the performance of biomaterials, but silk fibroin is mostly hydrophobic and interacts nonspecifically with cells and proteins. Silk functionalised with hydrophilic polymers reduces attachment, but the low number of reactive sites makes achieving a uniform conjugation a persistent challenge. This work presents a new approach to grow brush-like polymers from the surface of degradable silk films, where the films were enriched with hydroxyl groups, functionalised with an initiator, and finally reacted with acrylate monomers using atom transfer radical polymerisation. Two different routes to hydroxyl enrichment were investigated, one involving reaction with ethylene oxide (EO) and the other using a two-step photo-catalysed oxidation reaction. Both routes increased surface hydrophilicity, and hydrophilic monomers containing either uncharged (poly(ethylene glycol), PEG) pendant groups or zwitterionic pendant groups were polymerised from the surfaces. The initial processing of the films to induce beta sheet structures was found to impact the success of the polymerizations. Compared to the EO modified or unmodified silk surfaces, the oxidation reaction resulted in more polymer conjugation and the surfaces appear more uniform. Mesenchymal stem cell and protein attachment were the lowest on polymers grown from oxidised surfaces. PEG-containing brush-like polymers displayed lower protein attachment than surfaces conjugated with PEG using a previously reported "grafting to" method, but polymers containing zwitterionic side chains displayed both the lowest contact angles and the lowest cell and protein attachment. This finding may arise from the interactions of the zwitterionic pendant groups through their permanent dipoles and is an important finding because PEG is susceptible to oxidative damage that can reduce efficacy over time. These modified silk materials with lower cell and protein attachments are envisioned to find utility when enhanced diffusion around surfaces is required, such as in drug delivery implants.

Increasing the Lifetime of Insulin Cannula with Antifouling and Nitric Oxide Releasing Properties.

Many Type 1 diabetes patients utilize insulin pumps, which rely on a small subcutaneous insulin infusion cannula. However, insulin cannulas still suffer from infection and inflammation, which impacts the wear time of the insulin cannula, reduces the efficiency of insulin infusion, and requires frequent rotation of the insulin infusion site. Infection and inflammation of continuous insulin infusion pump therapy are growing issues and are estimated to cost billions of dollars globally each year. This study aims to develop a potent antibacterial and antifouling insulin cannula with a synergistic effect of bioinspired polymers, integrating antifouling slippery, liquid-infused porous surface technology with an active nitric oxide (NO) releasing polymer. The cannulas were developed by impregnating the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil (Si) in commercial medical-grade silicone rubber (SR) tubing (SR-SNAP-Si) via a solvent-impregnation process. The efficiency of the SR-SNAP-Si to reduce protein adsorption and provide antibacterial properties against Staphylococcus aureus and Staphylococcus epidermidis were studied using in vitro bioassays. The SR-SNAP-Si cannula released NO for more than 14 d at physiological levels and were stable during storage for 30 d at room temperature. Scanning electron microscopy images revealed no observable changes to the material surface after the solvent impregnation process. The infusion of silicone oil significantly reduced the protein adsorption on the cannula by 66.40%, and the NO release reduced the viable bacterial cell adhesion of S. epidermidis and S. aureus after 24 h by 94.89% and 99.77%, respectively, as compared to SR controls. This insulin cannula provided continuous NO release and an antifouling interface for more than 14 d and exhibited significant reduction in protein and bacterial adhesion. This method of developing dual-function nitric oxide releasing and antifouling surface for subcutaneous insulin infusion cannulas holds great potential to reduce infection and inflammation associated with insulin pump delivery systems.

Surface-Functionalized Polypropylene Surgical Mesh for Enhanced Performance and Biocompatibility.

Polypropylene (PP) surgical mesh has attracted vast attention due to its chemical inertness and excellent mechanical properties. However, improvement is necessary to enhance its biocompatibility and to prevent unwanted tissue adhesion. This study addresses these issues through surface modification of plasma-activated PP mesh with a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer. Reaction time and monomer concentration have been optimized to achieve the optimal biocompatibility with reduction in protein adsorption. Attenuated total reflection-Fourier transform infrared spectra confirmed the grafting of the MPC polymer (PMPC) to the plasma-activated polypropylene (PPP) mesh. Scanning electron microscopy images and energy-dispersive X-ray (EDX) line spectra exhibited morphological changes and specifically PMPC grafting to the surface of PPP mesh, due to the presence of a significant amount of phosphorus (P) on the grafted PPP mesh. PMPC-grafted polypropylene (PPP-PMPC) showed a significant reduction in contact angle as well as the amount of adsorbed bovine serum albumin (BSA) protein in comparison with pristine PP mesh. The highest reduction in protein adsorption and the lowest contact angle were achieved at the monomer concentration of 0.3 M and the reaction time of 90 min. A longer reaction time and higher monomer concentration resulted in clogging within the mesh pores. MTT assay results (∼90% cell viability) confirmed the nontoxicity of the PMPC-grafted mesh, while optical microscopic and SEM images showed increased resistance of cell attachment to the surface of PMPC-grafted mesh. The results show that PPP-PMPC can be a promising biomaterial to address the current issues in biocompatibility and reduction in adhesion after surgery.

Zwitterionic polymer/polydopamine coating reduce acute inflammatory tissue responses to neural implants

The inflammatory brain tissue response to implanted neural electrode devices has hindered the longevity of these implants. Zwitterionic polymers have a potent anti-fouling effect that decreases the foreign body response to subcutaneous implants. In this study, we developed a nanoscale anti-fouling coating composed of zwitterionic poly (sulfobetaine methacrylate) (PSB) and polydopamine (PDA) for neural probes. The addition of PDA improved the stability of the coating compared to PSB alone, without compromising the anti-fouling properties of the film. PDA-PSB coating reduced protein adsorption by 89% compared to bare Si samples, while fibroblast adhesion was reduced by 86%. PDA-PSB coated silicon based neural probes were implanted into mouse brain, and the inflammatory tissue responses to the implants were assessed by immunohistochemistry one week after implantation. The PSB-PDA coated implants showed a significantly decreased expression of glial fibrillary acidic protein (GFAP), a marker for reactive astrocytes, within 70 μm from the electrode-tissue interface (p < 0.05). Additionally, the coating reduced the microglia activation as shown in decreased Iba-1 and lectin staining, and improved blood-brain barrier integrity indicated by reduced immunoglobulin (IgG) leakage into the tissue around the probes. These findings demonstrate that anti-fouling zwitterionic coating is effective in suppressing the acute inflammatory brain tissue response to implants, and should be further investigated for its potential to improve chronic performance of neural implants.

Stabilised aluminium phosphate nanoparticles used as vaccine adjuvant

Aluminium phosphate is a commonly used adjuvant consisting of heterogeneously sized aggregates up to several micrometers. However, aluminium phosphate nanoparticles may exhibit an improved adjuvant effect. In this study, nanoparticles were made by sonication of commercially available aluminium phosphate adjuvant, resulting in particles with a size (Z-average diameter) between 200–300 nm and a point of zero charge of 4.5. To prevent reaggregation, which occurred within 14 days, a screening of excipients was performed to identify stabilisers effective under physiological conditions (pH 7.4, 290 mOsm). The amino acids threonine, asparagine, and L-alanyl-L-1-aminoethylphosphonic acid (LAPA) stabilised sonicated aluminium phosphate. Particle sizes remained stable between 400–600 nm at 37 °C during 106 days. Contrarily, arginine induced strong reaggregation to a particle size larger than 1000 nm. The stability of aluminium phosphate nanoparticles was strongly affected by the pH. Aggregation mainly occurred below pH 7. The adsorption capacity, a potentially relevant parameter for adjuvants, was slightly reduced in the presence of asparagine, when using a model antigen (lysozyme). LAPA, arginine, threonine and aspartic acid reduced protein adsorption significantly. The adjuvant effect of aluminium phosphate nanoparticles was studied by immunisation of mice with diphtheria toxoid adjuvanted with the aluminium phosphate nanoparticles. The presence of LAPA, threonine, aspartic acid or asparagine did not alter diphtheria toxoid-specific antibody or toxin-neutralising antibody titres. Arginine increased diphtheria toxoid-specific antibody titres but not toxin-neutralising antibody titres. In conclusion, aluminium phosphate nanoparticles were stabilised by particular amino acids and induced an adjuvant effect comparable to that of aluminium phosphate microparticles.

Surface Modification by Polyzwitterions of the Sulfabetaine-Type, and Their Resistance to Biofouling.

Films of zwitterionic polymers are increasingly explored for conferring fouling resistance to materials. Yet, the structural diversity of polyzwitterions is rather limited so far, and clear structure-property relationships are missing. Therefore, we synthesized a series of new polyzwitterions combining ammonium and sulfate groups in their betaine moieties, so-called poly(sulfabetaine)s. Their chemical structures were varied systematically, the monomers carrying methacrylate, methacrylamide, or styrene moieties as polymerizable groups. High molar mass homopolymers were obtained by free radical polymerization. Although their solubilities in most solvents were very low, brine and lower fluorinated alcohols were effective solvents in most cases. A set of sulfabetaine copolymers containing about 1 mol % (based on the repeat units) of reactive benzophenone methacrylate was prepared, spin-coated onto solid substrates, and photo-cured. The resistance of these films against the nonspecific adsorption by two model proteins (bovine serum albumin—BSA, fibrinogen) was explored, and directly compared with a set of references. The various polyzwitterions reduced protein adsorption strongly compared to films of poly(n-butyl methacrylate) that were used as a negative control. The poly(sulfabetaine)s showed generally even somewhat higher anti-fouling activity than their poly(sulfobetaine) analogues, though detailed efficacies depended on the individual polymer–protein pairs. Best samples approach the excellent performance of a poly(oligo(ethylene oxide) methacrylate) reference.

Dual-functional antimicrobial coating based on a quaternary ammonium salt from rosin acid with in vitro and in vivo antimicrobial and antifouling properties

Bacterial colonization and biofilm formation on indwelling medical devices potentially cause serious and life-threatening infections. Technologies to prevent bacterial colonization and biofilm formation on biomedical devices are in great demand. Here, we report the preparation of coating monomers by conjugating rosin acid-derived maleopimaric acid quaternary ammonium cation (MPA-N+) with different chain of lengths allyloxy polyethylene glycol (APEG; either MW 1200 or 2400). The monomers of the cation plus its linker conjugates (APEG1200/2400-MPA-N+) were further grafted onto the surface of silicone rubber slides (PDMS) via plasma/UV-induced surface polymerization to form antimicrobial and antifouling coatings. The dual-functional coatings exhibited excellent antimicrobial activities against gram-negative and positive bacteria, and they effectively prevented biofilm formation. The coatings also greatly reduced protein adsorption and platelet adhesion, indicating their excellent antifouling capability. In addition, the APEG1200/2400-MPA-N+ cation coatings were biocompatible towards mammalian cells, as shown by in vitro cytotoxicity assays using rabbit erythrocytes and attached human aorta smooth muscle cells. In addition, the APEG2400-MPA-N+ coating exhibited significant anti-infective activity in a rodent subcutaneous infection model. We show that the APEG2400-MPA-N+ coating is an effective strategy for the prevention of infections associated with indwelling biomedical devices.

Zwitterionic poly-carboxybetaine coating reduces artificial lung thrombosis in sheep and rabbits

Current artificial lungs fail in 1–4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N = 5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220–300 s (N ≥ 5). Here, DOPA-pCB reduced fibrin formation (p = 0.06) and gross thrombus formation by 59% (p < 0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs. Statement of SignificanceChronic lung diseases lead to 168,000 deaths each year in America, but only 2300 lung transplantations happen each year. Hollow fiber membrane oxygenators are clinically used as artificial lungs to provide respiratory support for patients, but their long-term viability is hindered by surface-induced clot formation that leads to premature device failure. Among different coatings investigated for blood-contacting applications, poly-carboxybetaine (pCB) coatings have shown remarkable reduction in protein adsorption in vitro. However, their efficacy in vivo remains unclear. This is the first work that investigates various pCB-coating methods on artificial lung surfaces and their biocompatibility in sheep and rabbit studies. This work highlights the promise of applying pCB coatings on artificial lungs to extend its durability and enable long-term respiratory support for lung disease patients.

Broad-Spectrum Anti-Adhesive Coating Based on an Extracellular Polymer from a Marine Cyanobacterium.

Medical device-associated infections are a major health threat, representing about half of all hospital-acquired infections. Current strategies to prevent this problem based on device coatings with antimicrobial compounds (antibiotics or antiseptics) have proven to be insufficient, often toxic, and even promoting bacterial resistance. Herein, we report the development of an infection-preventive coating (CyanoCoating) produced with an extracellular polymer released by the marine cyanobacterium Cyanothece sp. CCY 0110. CyanoCoating was prepared by spin-coating and its bacterial anti-adhesive efficiency was evaluated against relevant etiological agents (Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Escherichia coli) and platelets, both in the presence or absence of human plasma proteins. CyanoCoating cytotoxicity was assessed using the L929 fibroblasts cell line. CyanoCoating exhibited a smooth topography, low thickness and high hydrophilic properties with mild negative charge. The non-cytotoxic CyanoCoating prevented adhesion of all the bacteria tested (≤80%) and platelets (<87%), without inducing platelet activation (even in the presence of plasma proteins). The significant reduction in protein adsorption (<77%) confirmed its anti-adhesive properties. The development of this anti-adhesive coating is an important step towards the establishment of a new technological platform capable of preventing medical device-associated infections, without inducing thrombus formation in blood-contacting applications.

Effects of single species versus multispecies periodontal biofilms on the antibacterial efficacy of a novel bioactive Class-V nanocomposite

ObjectiveThe objectives of this studywere to: (1) develop a novel bioactive nanocomposite for Class V restorations with subgingival margins to inhibit periodontal pathogens; and (2) investigate if the bioactive nanocomposite could inhibit multi-species periodontal biofilms with a potency as strong as that against single species biofilms. MethodsNanocomposite was fabricated using dimethylaminohexadecyl methacrylate (DMAHDM), 2-methacryloyloxyethyl phosphorylcholine (MPC) and nanoparticles of amorphous calcium phosphate (NACP). Biofilms with 1, 3, 6 and 9 species of periodontal pathogens were grown on the composites and tested for live/dead staining, colony-forming units (CFU), metabolic activity, and biofilm matrix polysaccharide production. ResultsThe bioactive composite reduced protein adsorption by an order of magnitude (p < 0.05) and greatly reduced biofilm viability. It decreased the biofilm CFU by more than 3 orders of magnitude for all four types of periodontal biofilms, compared to control composite. With increasing the biofilm species from 1 to 9, the antibacterial efficacy of DMAHDM composite decreased; the CFU reduction folds decreased from 947 folds to 44 folds. In contrast, the MPC + DMAHDM composite maintained a CFU reduction folds of greater than 3000, showing a similar antibacterial potency from 1 to 9 species in the biofilms (p > 0.1). ConclusionDual agents MPC + DMAHDM achieved the greatest inhibition in biofilm, without decreasing its antibacterial potency when the biofilm species was increased from 1 to 9. A single agent became less effective when the biofilm species was increased from 1 to 9. SignificanceThe multifunctional MPC + DMAHDM composite is promising for root caries treatment and Class V restorations with subgingival margins to effectively inhibit multispecies periodontal biofilms, combat periodontitis and protect the periodontium.

Anti-biofouling and functionalizable bioinspired chitosan-based hydrogel coating via surface photo-immobilization

Zwitterionic polymer is a new generation of anti-fouling materials with its good resistance to protein and bacterial adhesion. Constructing the anti-fouling surfaces with zwitterionic polymer has been regarded as an effective approach for improving the biocompatibility and biofunctionality of clinic devices. Herein, we reported a facile approach to construct a biodegradable anti-biofouling and functionalizable hydrogel coating via photo-immobilization using commercial polyethylene terephthalate (PET) films as the substrate, based on zwitterionic glycidyl methacrylate-phosphorylcholine-chitosan (PCCs-GMA). The surface structure and physicochemical properties of zwitterionic PCCs-GMA hydrogel coating were investigated by X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM) and static water contact angle measurement, and its functionalizable sites were detected by fluorescence labeling. Compared with the pristine PET and cationic chitosan - GMA and hydroxypropyltrimethyl ammonium chloride chitosan (HTCC) - GMA hydrogel coatings, zwitterionic PCCs-GMA hydrogel coating exhibited excellent biocompatibility, and significantly reduced protein adsorption for three model proteins of fibrinogen, immunoglobulin and lysozyme, repelled platelet adhesion, as well as showed a high resistance to bacterial attachment of Escherichia coli and Staphylococcus aureus and superior anti-fouling properties to MRC-5 cells. The results indicated that photo-immobilized zwitterionic PCCs-GMA hydrogel coating has perspective as a dual functional platform with integrated antifouling and further biofunctional properties for various biomedical applications.

Thermo-responsive nanofibrous composite membranes for efficient self-cleaning of protein foulants

This study developed a self-clean thermo-responsive nanofibrous poly(vinylidene fluoride) (PVDF)/nylon-6,6/poly(N-isopropylacrylamide) (PNIPAAm) composite ultrafiltration membrane consisting of a nylon-6,6/PNIPAAm functional nanofibre layer integrated into a PVDF substrate. The morphological analysis showed the presence of electrospun nano-nets branching out from the main nanofibres as PNIPAAm concentration increased, affecting the pore size distribution and solute rejection. The PVDF/nylon-6,6/PNIPAAm membranes showed improved surface hydrophilicity below the low critical solution temperature (LCST) and strong thermo-switchability. With bovine serum albumin (BSA) as the model foulant, the rejection of the 4 wt% PNIPAAm membranes was greatly improved to above 96%. Through a two-cycle ultrafiltration study using feed solution containing BSA and CaCl2, the membrane with 4 wt% PNIPAAm showed superior recovery of water permeance up to 97% assisted with temperature-change cleaning, compared to the control membrane that only recovered 56%. Filtration experiments with and without intermediate temperature-change cleaning proved that the anti-fouling mechanism of the PNIPAAm membranes was strongly associated with surface wettability and rapid conformation of PNIPAAm polymer chains induced by volume-phase transition, resulting in reduced protein adsorption and ‘shaking-off’ of the absorbed proteins from the membrane surface. Such smart responsive membranes have great potential for the development of easy-to-clean membranes for food and wastewater treatment.

Cu nanoparticles constrain segmental dynamics of cross-linked polyethers: a trade-off between non-fouling and antibacterial properties.

Copper has a strong bactericidal effect against multi-drug resistant pathogens and polyethers are known for their resistance to biofilm formation. Herein, we combined Cu nanoparticles (NPs) and a polyether plasma polymer in the form of nanocomposite thin films and studied whether both effects can be coupled. Cu NPs were produced by magnetron sputtering via the aggregation in a cool buffer gas whereas polyether layers were synthesized by Plasma-Assisted Vapor Phase Deposition with poly(ethylene oxide) (PEO) used as a precursor. In situ specific heat spectroscopy and XPS analysis revealed the formation of a modified polymer layer around the NPs which propagates on the scale of a few nanometers from the Cu NP/polymer interface and then transforms into a bulk polymer phase. The chemical composition of the modified layer is found to be ether-deficient due to the catalytic influence of copper whereas the bulk polymer phase exhibits the chemical composition close to the original PEO. Two cooperative glass transition phenomena are revealed that belong to the modified polymer layer and the bulk phase. The former is characterized by constrained mobility of polymer segments which manifests itself via a 30 K increase of dynamic glass transition temperature. Furthermore, the modified layer is characterized by the heterogeneous structure which results in higher fragility of this layer as compared to the bulk phase. The Cu NPs/polyether thin films exhibit reduced protein adsorption; however, the constrained segmental dynamics leads to the deterioration of the non-fouling properties for ultra-thin polyether coatings. The films are found to have a bactericidal effect against multi-drug resistant Gram-positive Methicillin-Resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa.

Novel multifunctional nanocomposite for root caries restorations to inhibit periodontitis-related pathogens

ObjectivesThe objectives of this study were to: (1) develop a novel multifunctional composite with nanoparticles of silver (NAg), 2-methacryloyloxyethyl phosphorylcholine (MPC), dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP); and (2) investigate biofilm-inhibition via the multifunctional nanocomposite against three species of periodontal pathogens for the first time. MethodsThe multifunctional nanocomposite was fabricated by incorporating NAg, MPC, DMAHDM and NACP into the resin consisting of pyromellitic glycerol dimethacrylate (PMDGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA). Three species (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum) were tested for metabolic activity (MTT), live/dead staining, polysaccharide production and colony-forming units (CFU) of biofilms grown on resins. ResultsIncorporation of 0.08% to 0.12% NAg, 3% MPC, 3% DMAHDM and 30% NACP did not compromise the mechanical properties of the composite (p > 0.1). The multifunctional nanocomposite reduced protein adsorption to nearly 1/10 of that of a commercial control (p < 0.05). For all three species, the biofilm CFU was reduced by about 5 and 1 orders of magnitude via the nanocomposite containing NAg + MPC + DMAHDM, compared to commercial control and the composite with MPC + DMAHDM, respectively. ConclusionsThe novel multifunctional nanocomposite achieved the greatest reduction in metabolic activity, polysaccharide and biofilm growth of three periodontal pathogens. Clinical significanceThe strongly-antibacterial, multifunctional composite is promising for treating root lesions, alleviating periodontitis and protecting the periodontal tissues.

Novel self-etch adhesive with antibacterial and protein-repellent functions to prevent enamel demineralization.

Enamel demineralization is the most undesired side-effect of fixed orthodontic treatments. This study were to develop a novel adhesive that is self-etching instead of using the traditional etching method, and to form a sealant on the enamel to prevent demineralization. 2-methacryloyloxyethyl phosphorylcholine (MPC) and quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM) were mixed into a self-etch adhesive (Adper Easy One, 3M, St. Paul, MN, USA; referred to as AEO). Enamel shear bond strength (SBS) was measured. Protein adsorption onto the resins was measured. An oral microcosm biofilm model with saliva was tested. Incorporation of 7.5% MPC and 5% DMAHDM into AEO did not reduce the SBS (p>0.1). AEO with 7.5% MPC+5% DMAHDM had protein adsorption that was only 1/18 that of AEO control. AEO with 7.5% MPC+5% DAMHDM had much stronger antibacterial properties (p<0.05). In conclusion, the new self-etch adhesive with MPC and DAMHDM greatly reduced protein adsorption and inhibited biofilm viability.

Immobilization of functional polymers on poly(4-benzoyl-pxylylene-co-p-xylylene) films via photochemical conjugation for modulation of cell adhesion.

Surface modification with functional materials, such as anti-fouling or thermal responsive polymers, on biomedical devices benefits their clinical performance. Simple and versatile technologies, which could be applied to a wide variety of substrates, are still highly desirable. Chemical vapor deposition (CVD) of 4-benzoyl-[2,2]paracyclophane (Benzoyl-PPX) layers attracts much attention because the photoreactive platform could be deposited onto almost every substrate for the conjugation of functional molecules. In this study, poly(ethylene glycol) (PEG) was conjugated onto Benzoyl-PPX via UV illumination. The deposited PEG films could effectively reduce protein adsorption and cell attachment. The low-fouling properties of the PEG films were positively correlated with the molecular weight and concentration of PEG. We found that a PEG film, thicker than 16 nm and with a water contact angle of 30°, is a prerequisite for effective inhibition of cell attachment. We also demonstrated that the PEG coating was stable under acidic and basic environments. Furthermore, poly(N-isopropyl acrylamide), PNIPAAm, could be also tethered on the Benzoyl-PPX via UV illumination, and possessed thermal-responsive properties. Intact cell sheets could be released from the PNIPAAm film by decreasing culture temperature. The results indicate that Benzoyl-PPX is an excellent photoreactive platform for the conjugation of functional polymers for modulation of cell attachment.