Low Protein Adsorption Research Articles

Cell-inspired selective potassium removal towards hyperkalemia therapy by microphase-isolated core-shell microspheres.

Hyperkalemia is a common metabolic problem in patients with chronic kidney disease. Although oral medications and hemodialysis are clinically applied for lowering serum potassium, the intrinsic limitations encourage alternative therapy in the trend of adsorbent-based miniaturized blood purification devices. Cells serve as the biological K+ storage units that accumulate K+ through multiple mechanisms. Inspired by cells, our strategy aims at favorable permeation and enrichment of K+ in the microsphere. We incorporate cation-affinitive groups into core-shell structures with submicron-sized phase separation. These nano-spaced side-groups cooperate to form interlinked clusters, where crown ethers with Angstrom-scale ring for size-matched complexation, while ionic sulfonic acid groups for hydrophilicity and charge-buffering. The unique structure with such non-covalent interactions facilitates K+ for permeation across the shell and binding to the core while also ensuring mechanical strength and anti-swelling durability in biofluids. The microspheres exhibit high selectivity ratios of K+ (SK/Na, SK/Ca, SK/Mg up to 9.8, 21.6, and 17.7). As column adsorbents for hemoperfusion simulation, they effectively lower elevated K+ levels to the normal range (clearance rates up to 44.4%/45.3% for hyperkalemic human serum/blood). Blood compatibility tests show low protein adsorption, preferable hemocyte compatibility, and anticoagulation property in vitro. This promising strategy has clinical potential for hyperkalemia in high-risk patients. STATEMENT OF SIGNIFICANCE: Hyperkalemia (serum potassium >5mmol/L) is a common complication in chronic renal failure patients. The limitations of existing treatments prompt a shift to wearable artificial kidney technology for clinical convenience and efficacy. Existing treatments have limitations, and we turn to adsorbent-based miniaturized blood purification devices in the prospect of wearable artificial kidney technology. There exists a lack of ion-specific adsorbents applied in extracorporeal circuits to redress electrolyte imbalances like hyperkalemia. Inspired by cells, we aim at the favorable permeation and enrichment of K+ by microspheres. The microspheres have a microphase-isolated core-shell structure, whose nano-spaced groups form cation-affinitive clusters. Selective K+ removal and blood compatibility are achieved. We expect this strategy to enlighten alternative hyperkalemia therapy for these high-risk patients.

A wash-free, elution-free and low protein adsorption paper-based material for nucleic acid extraction.

Nucleic acid detection technologies have been widely utilized for various diseases. Conventional laboratory tests are less suitable for use in resource-limited settings as they are time-consuming, high-cost, complex, and heavily dependent on benchtop equipment. Rapid nucleic acid detection methods that consist of rapid nucleic acid extraction steps could overcome these challenges. A paper-based platform has been utilized to develop various rapid nucleic acid extraction methods owing to its cost-effectiveness, portability, and easy-modification. However, the existing paper-based nucleic acid extraction technologies mainly focus on improving the adsorption capacity of nucleic acids without reducing the non-specific adsorption capacity of proteins. In this study, paper-based nucleic acid extraction technology with wash-free, elution-free, and low protein adsorption was developed. The fabrication of paper involves the mixing of polyethylene glycol (PEG)-modified cotton fiber, chitosan (COS)-modified cotton fiber, and cotton fiber to form PEG-modified cotton fiber/chitosan-modified cotton fiber/cotton fiber (PEG-CF/COS-CF/CF) paper by the wet molding method. The result showed that PEG-CF/COS-CF/CF paper has a desirable pore size (23.9 ± 4.03 μm), good mechanical strength (dry: 9.37 Mpa and wet: 0.28 Mpa), and hydrophilicity (contact angle: 42.6° ± 0.36°). NH3+ groups of COS and OH- groups of PEG were observed on its surface and the adsorption efficiency of nucleic acid in TE buffer was 42.48% ± 0.30%. The limit of detection of pure DNA with this PEG-CF/COS-CF/CF paper by qPCR was as low as 25 ng. Additionally, this platform could successfully extract nucleic acid from 30 μL of a saliva sample, highlighting its potential use for clinical sample testing. The proposed paper-based nucleic acid extraction platform shows tremendous potential for disease diagnosis in resource-limited settings.

Performance investigation of hydrophilic regenerated cellulose ultrafiltration membranes with excellent anti-fouling property via hydrolysis technology

To obtain ultrafiltration (UF) membranes with excellent separation performances and antifouling properties, regenerated cellulose (RC) membranes with intrinsic hydrophilicity and dense structures immensely attract the attention of researchers. Herein, a novel modified RC membrane, which has high water permeability and antifouling capability, is prepared using cellulose acetate (CA) via non-solvent induced phase separation (NIPS) and green hydrolysis technology. The as-prepared membranes were investigated comprehensively by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) analyses and protein adsorption, etc. As a result, the RC membranes showed higher hydrophilicity (WCA=25.95°), thus they possessed a lower protein adsorption value of 1.9 ± 0.1 μg/cm2. The filtration performances were evaluated by bovine serum albumin (BSA) and endotoxin separation with dead-end filtration system. The results exhibited greater selectivity of RC membranes that BSA rejection over 98% and endotoxin remove below 0.25 EU/mL, and excellent anti-fouling properties that the flux recovery rate (FRR) over 95% and even as high as 100%. Simultaneously, the common polyethersulfone (PES) composite membranes were prepared via NIPS technology, and comprehensively compared with RC membranes to provide a theoretical basis for the practical application of RC membranes in pharmaceutical and biotechnological industries.

Zwitterionic Polymer/Polydopamine Coating of Electrode Arrays Reduces Fibrosis and Residual Hearing Loss after Cochlear Implantation.

Since the first surgery 50 years ago, cochlear implantation (CI) is the major treatment for patients with severe sensorineural hearing loss. However, unexpected foreign body reactions (FBRs) after surgery are reported in 90% of CI recipients, resulting in the formation of fibrosis in the cochlea and progressive residual hearing loss. Zwitterion modification is universally used to reduce bio-fouling and suppress FBRs but never for CI. In the present study, a zwitterionic coating is developed, which is composed of poly sulfobetaine methacrylate (PSB) and polydopamine (PDA) for cochlear implants. The PSB-PDA coating shows a series of characters for an ideal anti-FBRs material, including super-hydrophilicity, low protein and cell adsorption, long-term stability, and high biocompatibility. Compared to the uncoated controls, PSB-PDA coating inhibits the activation of macrophages and reduces the release of inflammatory factors (TNF-α, IL-1β, NO) and fibrosis-related factors (TGF-β1, α-SMA, collagen I). PSB-PDA coated electrode arrays suppress fibrosis completely and preserve residual hearing significantly in rat CI models. These results suggest that PSB-PDA coating is a novel strategy for anti-fibrosis to improve the outcomes of CI.

Effect of poly(ethylene glycol) methacrylate on the ophthalmic properties of silicone hydrogel contact lenses

In this study, silicone hydrogels were synthesized via the photoinitiated free radical polymerization of 3-(methacryloyloxy)propyltris(trimethylsiloxy) silane (TRIS), 1-vinyl-2-pyrrolidinone (NVP), methacrylic acid (MAA), and poly(ethylene glycol) methacrylate (PEGMA), with ethylene glycol dimethacrylate (EGDMA) as the cross-linker and 2-hydroxy-2-methylbenzene acetone (D-1173) as the photoinitiator. The equilibrium water content (EWC) and oxygen permeability (Dk) of the synthesized silicone hydrogel polymers were linearly proportional to the hydrophilic PEGMA content. The high PEGMA content of the polymers led to a higher EWC, lower Dk, and lower contact angle. The highest Dk value of the soft lens was 73 barrers, which corresponded with the lowest EWC (31 %) value of the hydrogel without PEGMA. The stiffness of the hydrogel decreased with increasing PEGMA content. The silicone hydrogel adsorbed low amounts of lysozymes and human serum albumin (HSA) due to the anti-fouling properties of PEG moiety. In addition, the synthesized silicone hydrogels were non-cytotoxic as determined by an in vitro L929 fibroblast assay. Therefore, the TRIS-NVP-MAA-PEGMA hydrogel can be potentially used as a contact lens material with adjustable EWC, Dk, and low protein adsorption.

Fabrication of zein-based hydrophilic nanoparticles for efficient gene delivery by layer-by-layer assembly

As a natural biological macromolecule, zein has broad application prospects in drug delivery due to its unique self-assembly properties. In this work, zein/sodium alginate (Zein/SA) nanocomposites were prepared by a pH-cycle method, Then Zein/SA/PEI (ZSP) nanocomposites were prepared by efficient layer-by-layer assembly method, ZSP nanocomposite of higher transfection performance was further labeled by folic acid (FA). After characterizing the physicochemical properties of ZSP by various methods, the potential of ZSP as a gene delivery vehicle was explored in vitro. The results showed that ZSP had good dispersibility and stability, the diameter distribution was in the range of 124–203 nm, and it had a typical core-shell structure, which could effectively condensate DNA and protect it from nuclease hydrolysis. ZSP exhibited proton buffering capacity similar to PEI, lower cellular toxicity, lower protein adsorption and erythrocyte hemolysis effect than PEI. ZSP/pDNA complexes could be taken up by cells and exhibited higher transfection efficiency than PEI/DNA complexes at the same weight ratio. The transfection efficiency of the complex in HeLa and 293T cells can be improved by FA labeling, especially in HeLa cells. These results provide new perspective for the design and development of efficient zein-based gene delivery systems.

In vitro hemocompatibility and hemodialysis performance of hydrophilic ionic liquid grafted polyethersulfone hollow fiber membranes

Polymer-based hemodialyzers have been widely used to treat patients suffered from end stage renal disease clinically. Polyethersulfone (PES) is seen as one of the most important hemodialysis membrane materials. Numerous strategies have been done to increase the hemocompatibility of PES, but molecular chain modification of PES has been seldomly reported. In this work, a hydrophilic ionic liquid (IL) grafted PES (PES-g-IL) was used to prepare the hollow fiber membranes (HFMs). The structure and properties, including hemocompatibility, hemodialysis performance as well as the cytotoxicity of PES-g-IL HFMs were investigated systematically. It was found that PES-g-IL HFMs had higher porosity, lower protein adsorption, less platelet adhesion and longer clotting time than PES HFMs, indicating the enhanced hemocompatibility. Besides, both the toxins removal and BSA rejection of PES-g-IL HFMs were significantly higher than those of PES HFMs. Particularly, the middle molecule uremic toxin (lysozyme) clearance of PES-g-IL HFMs was twice higher than that of PES HFMs. At the same time, the BSA rejection of PES-g-IL HFMs achieved as high as 98%. Moreover, PES-g-IL showed negligible cytotoxicity. It is considered that the grafting of IL changed the microstructure and improved the hydrophilicity of PES-g-IL membranes, leading to the enhanced hemocompatibility, hemodialysis performance and cytocompatibility.

A Dense Layer of Polyethyleneglycol and Zwitterionic Bone Targeting Peptide on the Surface of Stereocomplex Polylactide-Polyethyleneglycol Nanoparticles Improves Shelf-storage Stability and the Serum Compatibility

The surface properties of nanoparticles (NPs) affect their stability and formation of the protein corona, which influence their targeting abilities. We evaluated these properties using bone (hydroxyapatite; HAP) targeting peptide on tamoxifen (TAM)-loaded stereocomplexformed polylactide-polyethyleneglycol (SC-PLA-PEG) NPs. Octaaspartic acid-octaglycine-cysteine (D8G8C) anionic derivative (Ani. pep.) and octa-aspartic acid-octa lysine-cysteine (D8K8C), a zwitterionic derivative (Zwi. pep.) were conjugated with SC-PLA-PEG NPs as HAP-targeting peptides. The addition of hydrophobic PLA homopolymers increased the surface PEG density on the NPs. Denser PEG chains on NPs decreased their specific surface area, reducing protein adsorption on the NPs and TAM release from NPs. NPs with dense PEG chains and Zwi. pep. showed superior shelf stability and lower protein adsorption than NPs with dense PEG chains and Ani. pep. in murine serum. Furthermore, the HAP-binding ability of NPs with Zwi. pep. was significantly higher than that of NPs with Ani. pep. These results indicate that decreasing the specific surface area and zwitterionization of HAP-targeting peptides on NPs are promising approaches to improve the serum compatibility and stability of NPs.

Rapid fabrication of zwitterionic sulfobetaine vinylimidazole-based monoliths via photoinitiated copolymerization for hydrophilic interaction chromatography

Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography. In this study, a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-1-propanesulfonate (SBVI) with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic system. Notably, the duration for the preparation of this novel monolith was as little as 5 min, which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated copolymerization. Moreover, these monoliths showed good morphology, permeability, porosity (62.4%), mechanical strength (over 15 MPa), column efficiency (51,230 plates/m), and reproducibility (relative standard deviations for all analytes were lower than 4.6%). Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based monolith. In particular, the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein adsorption. These excellent features seem to favor its application in bioanalysis. Therefore, the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex samples. In this study, we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.

Modeling Polyzwitterion-Based Drug Delivery Platforms: A Perspective of the Current State-of-the-Art and Beyond.

Drug delivery platforms are anticipated to have biocompatible and bioinert surfaces. PEGylation of drug carriers is the most approved method since it improves water solubility and colloid stability and decreases the drug vehicles’ interactions with blood components. Although this approach extends their biocompatibility, biorecognition mechanisms prevent them from biodistribution and thus efficient drug transfer. Recent studies have shown (poly)zwitterions to be alternatives for PEG with superior biocompatibility. (Poly)zwitterions are super hydrophilic, mainly stimuli-responsive, easy to functionalize and they display an extremely low protein adsorption and long biodistribution time. These unique characteristics make them already promising candidates as drug delivery carriers. Furthermore, since they have highly dense charged groups with opposite signs, (poly)zwitterions are intensely hydrated under physiological conditions. This exceptional hydration potential makes them ideal for the design of therapeutic vehicles with antifouling capability, i.e., preventing undesired sorption of biologics from the human body in the drug delivery vehicle. Therefore, (poly)zwitterionic materials have been broadly applied in stimuli-responsive “intelligent” drug delivery systems as well as tumor-targeting carriers because of their excellent biocompatibility, low cytotoxicity, insignificant immunogenicity, high stability, and long circulation time. To tailor (poly)zwitterionic drug vehicles, an interpretation of the structural and stimuli-responsive behavior of this type of polymer is essential. To this end, a direct study of molecular-level interactions, orientations, configurations, and physicochemical properties of (poly)zwitterions is required, which can be achieved via molecular modeling, which has become an influential tool for discovering new materials and understanding diverse material phenomena. As the essential bridge between science and engineering, molecular simulations enable the fundamental understanding of the encapsulation and release behavior of intelligent drug-loaded (poly)zwitterion nanoparticles and can help us to systematically design their next generations. When combined with experiments, modeling can make quantitative predictions. This perspective article aims to illustrate key recent developments in (poly)zwitterion-based drug delivery systems. We summarize how to use predictive multiscale molecular modeling techniques to successfully boost the development of intelligent multifunctional (poly)zwitterions-based systems.

Electrical monitoring of infection biomarkers in chronic wounds using nanochannels

Chronic wounds represent an important healthcare challenge in developed countries, being wound infection a serious complication with significant impact on patients’ life conditions. However, there is a lack of methods allowing an early diagnosis of infection and a right decision making for a correct treatment. In this context, we propose a novel methodology for the electrical monitoring of infection biomarkers in chronic wound exudates, using nanoporous alumina membranes. Lysozyme, an enzyme produced by the human immune system indicating wound infection, is selected as a model compound to prove the concept. Peptidoglycan, a component of the bacterial layer and the native substrate of lysozyme, is immobilized on the inner walls of the nanochannels, blocking them both sterically and electrostatically. The steric blocking is dependent on the pore size (20–100 nm) and the peptidoglycan concentration, whereas the electrostatic blocking depends on the pH. The proposed analytical method is based on the electrical monitoring of the steric/electrostatic nanochannels unblocking upon the specific degradation of peptidoglycan by lysozyme, allowing to detect the infection biomarker at 280 ng/mL levels, which are below those expected in wounds. The low protein adsorption rate and thus outstanding filtering properties of the nanoporous alumina membranes allowed us to discriminate wound exudates from patients with both sterile and infected ulcers without any sample pre-treatment usually indispensable in most diagnostic devices for analysis of physiological fluids.Although size and charge effects in nanochannels have been previously approached for biosensing purposes, as far as we know, the use of nanoporous membranes for monitoring enzymatic cleavage processes, leading to analytical systems for the specific detection of the enzymes has not been deeply explored so far. Compared with previously reported methods, our methodology presents the advantages of no need of neither bioreceptors (antibodies or aptamers) nor competitive assays, low matrix effects and quantitative and rapid analysis at the point-of-care, being also of potential application for the determination of other protease biomarkers.

Recycling protein selective adsorption on fluorine-modified surface through fluorine-fluorine interaction

Low surface energy materials with micro-nano structures have been widely developed to prevent non-specific adhesion of biomolecules. Herein we put forward a new approach based on the antifouling and self-assembly properties of fluorine components, to construct a non-specific protein resistance surface with selective protein adsorption property. Briefly, the antifouling surface (SN-F) was obtained by a simple one-step modification on silicon nanowire arrays (SiNWAs) with fluorine coupling agent 1 H,1 H,2 H,2 H-perfluorodecyltrimethoxysilane (FAS). And protein was fluorinated by conjugation with an amphiphilic fluoro-copolymer, produced from 2-methacrylamido glucopyranose (MAG) and trifluoroethyl methacrylate (TFEMA) via RAFT polymerization. The properties of the materials were characterized by 1H nuclear magnetic resonance (1H NMR), infrared spectroscopy (FTIR), water contact angle, and X-ray photoelectron spectroscopy (XPS) etc., and protein adsorption was investigated by protein content measurement, fluorescence detection, and electrophoresis. It was observed that the adsorption for native proteins on SN-F was at an extremely low level, while the adsorption for the fluoro-copolymer conjugated protein (PFG-BSA) was significantly increased. When the percentage of TFEMA in the fluoro-copolymer was as high as 52.0%, the fluorinated protein adsorbed on SN-F was more than 35 times of native proteins on the surface. Moreover, the platform could resist IgG adhesion in serum after the adsorption of fluorinated protein, and it could be recycled three times after 75% ethanol treatment. In conclusion, SN-F showed non-specific protein resistance through low surface energy and specific protein adsorption by fluorine-fluorine self-assembly. The fluorinated nanostructured platform has a great potential in controlling protein adsorption and release.

Photo-assisted generation of versatile zwitterionic carboxybetaine-based hypercrosslinked polymers for separation science

Zwitterionic super-hydrophilic polymeric monoliths showed fascinating attributes because of their excellent biocompatibility, hydrophilicity, and antifouling properties. However, their commercial developments are limited by their tedious preparation process and unsatisfactory performance. 1-Carboxy-N-methyl-N-di(2-methacryloyloxyethyl)methanaminium inner salt (CBMAX), an important zwitterionic functional monomer, which exhibits excellent hydrophilicity and extremely low protein adsorption from undiluted serum. However, no carboxybetaine based monolith has been reported to date. In this study, a rapid photo-assisted generation strategy based on a sole-monomer system (CBMAX being simultaneously used as monomer and crosslinker) was proposed for preparing versatile hyper-crosslinked zwitterionic carboxybetaine polymers in capillaries within only 5 min. It is significantly faster than the conventional sole-monomer (1 h) and multi-monomer system (over 12 h) via thermally-initiated polymerization approach. Moreover, a high column efficiency of 82,000 plates/m, abundant electrostatic and hydrophilic interactions were achieved on the novel monolith due to the unique advantages of carboxybetaine. These excellent features were beneficial for the high-performance separation of various bioactive compounds (including nucleotide bases, phenols, benzoic acid and its derivatives, urea and allantoin) on this monolith. It is worth noting that this zwitterionic monolith exhibited good anti-protein adsorption ability as well as excellent enrichment capacity for N-glycopeptides from hIgG tryptic digest. In summary, the proposed photo-assisted generation strategy based on sole-monomer CBMAX is very successful and opens up a promising solution for the commercial development of zwitterionic super-hydrophilic polymeric monoliths.

Bio-Inspired Proanthocyanidins from Blueberries’ Surface Coating Prevents Red Blood Cell Agglutination on Urinary Silicon-Based Catheters

Thrombosis can cause the occlusion of implantable medical devices, leading to the rejection of the device and subsequent mortality. Thrombosis is primarily induced by red blood aggregation and coagulation. The administration of anticoagulant drugs is generally used as a treatment to avoid these processes. Adverse effects such as bleeding in the event of an anticoagulant overdose, osteoporosis associated with prolonged use, hypersensitivity, and hives have been reported. New strategies such as biomolecule surface functionalization have recently been studied to overcome these problems. In this study, we report a novel coating composed of polydopamine (PDA) and proanthocyanidins (PACs) from blueberry extract to avoid red blood aggregation in short-term use medical devices such as silicone catheters. We showed that PDA formed stable films on silicone surfaces and PACs could be immobilized on PDA layers using laccase as a catalyst. The PDA–PACs films decreased surface hydrophilicity, increased surface roughness, and decreased plasma protein adsorption. The films were stable in phosphate buffer saline (PBS) and cell culture media. Furthermore, red blood cell adsorption and aggregation decreased. These effects are attributed to changes in the membrane fluidity that influences adhesion, the steric hindrance of the layers, and the low adsorption of plasma proteins on the PAC layer.

Natural polyphenol-based nanoengineering of collagen-constructed hemoperfusion adsorbent for the excretion of heavy metals

Designing a hemoperfusion adsorbent for the excretion therapy of toxic heavy metals still remains a great challenge due to the biosafety risks of non-biological materials and the desired highly efficient removal capacity. Herein, inspired from the homeostasis mechanism of plants, natural polyphenols are integrated with collagen matrix to construct a polyphenol-functionalized collagen-based artificial liver (PAL) for heavy metals excretion and free radicals scavenging therapy. PAL presents high adsorption capacities for Cu2+, Pb2+, and UO22+ ions, up to 76.98 μmol g–1, 106.70 μmol g–1, and 252.48 μmol g–1, respectively. Remarkably, PAL possesses a high binding affinity for UO22+, Pb2+, and Cu2+ ions even in the complex serum environment with the presence of biologically-relevant ions (e.g., Mg2+, Ca2+ ions). Low hemolysis ratio (1.77%), high cell viability (> 85%), high plasma recalcification time (17.4 min), and low protein adsorption (1.02 μmol g–1) indicate outstanding biocompatibility of this material. This natural polyphenol/collagen-based fully bio-derived hemoperfusion adsorbent provides a novel and potentially applicable strategy for constructing a hemoperfusion adsorbent for heavy metal ions excretion therapy with efficiency and biosafety.

Preclinical testing of an anal bulking agent coated with a zwitterionic polymer in a fecal incontinence rat model.

Fecal incontinence is a disabling condition in which the passage of fecal material cannot be controlled. Although the condition is not life-threatening, it can seriously reduce the quality of life of a patient by isolating them from others. Though various surgical treatments are available for moderate to severe symptoms, a bulking agent is a minimally invasive technique that has attracted attention because of its safety and simple treatment process. However, the biocompatibility of bulking agent materials remains a central issue, with their durability questioned because immune responses and/or the circulatory system may remove the bulking agent in vivo. This study investigated a bulking agent composed of polydimethylsiloxane and hyaluronic acid as a microfiller and carrier gel, respectively. To improve the injectability of the bulking agent, the filler size was tuned using a suspension-based fabrication technique. To evade immune responses, the filler surface was treated with a zwitterionic polymer that simultaneously functionalized and stabilized the material interfaces. The resulting bulking agent exhibited good injectability and biocompatibility in vitro, with 58% lower protein adsorption and no cytotoxicity, leading to an improved bulking effect in a preclinical rat model compared with a bulking agent without surface treatment. These results illustrate the promising potential of bulking agents as a therapy for fecal incontinence with reduced foreign body reactions and long-lasting efficacy.

Self-targeting of zwitterion-based platforms for nano-antimicrobials and nanocarriers.

Self-targeting antimicrobial platforms have yielded new possibilities for the treatment of infectious biofilms. Self-targeting involves stealth transport through the blood circulation towards an infectious biofilm, where the antimicrobial platform penetrates and accumulates in a biofilm in response to a change in environmental conditions, such as local pH. In a final step, nano-antimicrobials need to be activated or the antimicrobial cargo of nanocarriers released. Zwitterions possess both cationic and anionic groups, allowing full reversal in zeta potential from below to above zero in response to a change in environmental conditions. Electrolyte-based platforms generally do not have the ability to change their zeta potentials from below to above zero. Zwitterions for use in self-targeting platforms are usually hydrophilic and have a negative charge under physiological conditions (pH 7.4) providing low adsorption of proteins and assisting blood circulation. However, near or in the acidic environment of a biofilm, they become positively-charged yielding targeting, penetration and accumulation in the biofilm through electrostatic double-layer attraction to negatively-charged bacteria. Response-times to pH changes vary, depending on the way the zwitterion or electrolyte is built in a platform. Self-targeting zwitterion-based platforms with a short response-time in vitro yield different accumulation kinetics in abdominal biofilms in living mice than platforms with a longer response-time. In vivo experiments in mice also proved that self-targeting, pH-responsive zwitterion-based platforms provide a feasible approach for clinical control of bacterial infections. Clinically however, also other conditions than infection may yield an acidic environment. Therefore, it remains to be seen whether pH is a sufficiently unique recognition sign to direct self-targeting platforms to an infectious biofilm or whether (additional) external targeting through e.g. near-infrared irradiation or magnetic field application is needed.

Laccase-catalyzed surface oxidation of poly(2-hydroxyethyl methacrylate) contact lens hydrogel using polyvinylamine-graft-TEMPO as mediator

Surface oxidation is a commonly used surface modification method for macromolecular biomaterials, which can increase the surface hydrophilicity and biocompatibility, and provide active sites for subsequent functional modifications. The nitroxyl radical, as represented by TEMPO, could act as an electron transfer mediator in the catalytic oxidation reaction in aqueous phase. By immobilizing TEMPO on a water-soluble polymer carrier polyvinylamine (PVAm) and using laccase as a catalyst, the surface of poly(2-hydroxyethyl methacrylate) (pHEMA) contact lens hydrogel can be selectively oxidized. Herein, polyvinylamine-graft-TEMPO was used as a polymeric electron transfer mediator to confine the oxidation reaction within the surface of the pHEMA hydrogel. The oxidized hydrogel with surface aldehydes was subsequently coated with hyaluronic acid, which gained low rate of water loss and low protein adsorption. This surface oxidation method can provide new ways for the activation, modification, and function expansion for the surface of polymeric biomaterials especially contact lens hydrogels.

Surface Characterisation of Human Serum Albumin Layers on Activated Ti6Al4V.

Adpsortion of protein layers on biomaterials plays an important role in the interactions between implants and the bio-environment. In this context, human serum albumin (HSA) layers have been deposited on modified Ti6Al4V surfaces at different ultraviolet (UV-C) irradiation times to observe possible changes in the adsorbed protein layer. Protein adsorption was done from solutions at concentraions lower than the serum protein concentration, to follow the surface modifications at the beginning of the albumin adhesion process. For this purpose, the surface of the protein-coated samples has been characterized by time of flight secondary ion mass spectrometry (ToF-SIMS), contact angle and zeta potential measurements. The results obtained show a reduction in the total surface tension and zeta potential of samples treated with UV-C light when coated with a protein layer. Furthermore, the UV-C light treatment applied to titanium alloy surfaces is able to modify the conformation, orientation and packing of the proteins arranged in the adsorbed layer. Low irradiation time generates an unstable surface with the lowest protein adsorption and the highest hydrophobic/hydrophilic protein ratio, indicating a possible denaturalization of the protein on these surfaces. However, surface changes are stabilized after 15 h or UV-C irradiation, favoring the protein adsorption through electrical interactions.

Fabrication and properties of polyhydroxybutyrate/kaolin nanocomposites and evaluation of their biocompatibility for biomedical applications

AbstractThe polyhydroxybutyrate biopolymer nanocomposites (C1–C10) were fabricated by solvent casting method with different loading of kaolin and polyethylene glycol. Scanning electron microscopy showed that the microstructure of the composites varied with different kaolin loading. X‐ray diffraction and Fourier transform infrared spectroscopy analysis confirm the presence of kaolin in the polymer matrix due to the intercalation and formation of hydrogen bond. The contact angle of the nanocomposites decreased with increasing kaolin loading indicating an improvement in wettability of the nanocomposites. Thermogravimetric and differential scanning calorimetry analysis showed that the Tmax and Tm of the nanocomposites increased with increasing kaolin loading. The mechanical property of the nanocomposite fabricated with 10 wt% kaolin (C10) was found to have identical mechanical property with natural bone that was selected as an optimum nanocomposite. The nanocomposite showed prolonged blood clotting time exhibiting anticoagulant nature of the nanocomposite. Moreover, low protein adsorption (168 ± 8 μg/cm2), suppressed platelet adhesion (75 ± 2 × 109 platelets/cm2) and less complement activation (118 ± 5 mg/dl for C3 and 658 ± 5 mg/dl for C4) showed the improvement in surface properties of the nanocomposite. In vitro bioactivity studies revealed the formation of hydroxyapatite layer on the surface of the nanocomposites. Eventually, the nanocomposites (C10) showed no cytotoxic effect on MG‐63 cells as tested through MTT assay and it is biologically safe.