A Hybrid Peptide Amphiphile Fiber PEG Hydrogel Matrix for 3D Cell Culture

Since the traditional 2D surface for cell growth has been shown to be increasingly insufficient in contemporary cell biology, more and more research is performed on 3D matrices that can better represent the natural extracellular matrix (ECM) in many aspects. To create such a complex nonuniform 3D matrix, four‐armed polyethylene glycol with azides and (1R,8S,9S)‐bicyclo[6.1.0]non‐4‐yn‐9‐yl groups is functionalized to form the hydrogel basis. Together with these, a matrix metalloproteinase cleavable peptide sequence as a functional motif is also built in to add degradability to the hydrogel. In addition, self‐assembled peptide amphiphile (PA) fibers containing a cellular binding peptide sequence (RGDS) are encapsulated in the hydrogel to mimic the natural fibrous structure of the ECM and to stimulate cell adhesion. Rheology studies confirm that the polymer dissolved in the PA fiber solution forms a stable hydrogel with acceptable mechanical properties (G′ = 3.8 kPa). In addition, it is shown that this hydrogel network is degradable under the action of a metalloproteinase enzyme. Finally, the hybrid hydrogel is used to culture and it is demonstrated that both HeLa cells and human mesenchymal stem cells show adherence, good viability, and a well‐spread shape inside the hybrid hydrogel after 5 days of incubation when all components are present.     

Extended Solution Gate OFET‐Based Biosensor for Label‐Free Glial Fibrillary Acidic Protein Detection with Polyethylene Glycol‐Containing Bioreceptor Layer

A novel organic field effect transistor (OFET)‐based biosensor is described for label‐free glial fibrillary acidic protein detection. This study reports the first use of an extended solution gate structure where the sensing area and the organic semiconductor are separated, and a reference electrode is not needed. Different molecular weight polyethylene glycols (PEGs) are mixed into the bioreceptor layer to help extend the Debye screening length. The drain current change is significantly increased with the help of higher molecular weight PEGs, as they are known to reduce the dielectric constant. This study also investigates the sensing performance under different gate voltage (V _g). The sensitivity increases after the V _g is decreased from ?5 to ?2 V because the lower V _g is much closer to the OFET threshold voltage and the influence of attached negatively charged proteins becomes more apparent. Finally, the selectivity experiments toward different interferents are performed. The stability and selectivity are promising for clinical applications.     

A Novel Photoscissile Poly(ethylene glycol)‐Based Hydrogel

A novel eight‐branched poly(ethylene glycol), PEG, macromer having a nitrocinnamate moiety as a pendant group was synthesized and found to form a photoscissile hydrogel upon exposure to 365 nm radiation in the absence of photoinitiators or catalysts. The processes of photocrosslinking and photocleavage were clearly characterized by environmental scanning electron microscopy (ESEM).     

Lipoplex‐Loaded Microbubbles for Gene Delivery: A Trojan Horse Controlled by Ultrasound

Cationic poly(ethylene glycol)ylated (PEGylated) liposomes are one of the most important gene transfer reagents in non‐viral gene therapy. However, the low transfection efficiencies of highly PEGylated lipoplexes currently hamper their clinical use. Recently, ultrasound has been used in combination with microbubbles to enhance the uptake of genes in different cell types. However, the gene transfer efficiency still remains low in these experiments. To overcome the limitations of both techniques, we present the attachment of PEGylated lipoplexes to microbubbles via biotin–avidin–biotin linkages. Exposure of these lipoplex‐loaded microbubbles to ultrasound results in the release of unaltered lipoplexes. Furthermore, these lipoplex‐loaded microbubbles exhibit much higher transfection efficiencies than “free” PEGylated lipoplexes or naked plasmid DNA (pDNA) when combined with microbubbles and ultrasound. Interestingly, the lipoplex‐loaded microbubbles only transfect cells when exposed to ultrasound, which is promising for space‐ and time‐controlled gene transfer. Finally, this novel Trojan‐horse‐like concept can also be exploited to achieve the ultrasound‐triggered release of nanoparticles containing other therapeutic agents such as anticancer drugs.     

Highly CO2‐Permeable and ‐Selective Membranes Derived from Crosslinked Poly(ethylene glycol) and Its Nanocomposites

Crosslinked poly(ethylene glycol diacrylate) (PEGda) oligomers differing in molecular weight, and their nanocomposites prepared with up to 10 wt.‐% methacrylate‐functionalized fumed silica (FS) or an organically‐modified nanoclay, have been examined as amorphous CO₂‐selective membranes. These novel materials have been characterized by dynamic rheology before and after crosslinking to ascertain the effect of incorporated FS on mechanical properties. The permeabilities of CO₂, H₂, N₂, and O₂ have been measured as functions of PEGda molecular weight, nanofiller content and temperature. In all cases, CO₂ displays relatively high permeability, coupled with high CO₂ selectivity, due to the specific interaction between quadrupolar CO₂ and the ether linkages along the PEG backbone, and the accompanying enhancement in CO₂ solubility. Variable‐temperature permeation exhibits Arrhenius behavior, and the activation energy for CO₂ permeation is found to be i) markedly lower than that of any of the other gases examined, and ii) independent of both PEGda molecular weight and nanofiller content.     

Modular Multifunctional Poly(ethylene glycol) Hydrogels for Stem Cell Differentiation

Synthetic polymers are employed to create highly defined microenvironments with controlled biochemical and biophysical properties for cell culture and tissue engineering. Chemical modification is required to input biological or chemical ligands, which often changes the fundamental structural properties of the material. Here, a simple modular biomaterial design strategy is reported that employs functional cyclodextrin nanobeads threaded onto poly(ethylene glycol) (PEG) polymer necklaces to form multifunctional hydrogels. Nanobeads with desired chemical or biological functionalities can be simply threaded onto the PEG chains to form hydrogels, creating an accessible platform for users. The design and synthesis of these multifunctional hydrogels are described, structure‐property relationships are elucidated, and applications ranging from stem cell culture and differentiation to tissue engineering are demonstrated.     

Hybrid 3D Printing of Synthetic and Cell‐Laden Bioinks for Shape Retaining Soft Tissue Grafts

Despite recent advances in clinical procedures, the repair of soft tissue remains a reconstructive challenge. Current technologies such as synthetic implants and dermal flap autografting result in inefficient shape retention and unpredictable aesthetic outcomes. 3D printing, however, can be leveraged to produce superior soft tissue grafts that allow enhanced host integration and volume retention. Here, a novel dual bioink 3D printing strategy is presented that utilizes synthetic and natural materials to create stable, biomimetic soft tissue constructs. A double network ink composed of covalently cross‐linked poly(ethylene) glycol and ionically cross‐linked alginate acts as a physical support network that promotes cell growth and enables long‐term graft shape retention. This is coupled with a cell‐laden, biodegradable gelatin methacrylate bioink in a hybrid printing technique, and the composite scaffolds are evaluated in their mechanical properties, shape retention, and cytotoxicity. Additionally, a new shape analysis technique utilizing CloudCompare software is developed that expands the available toolbox for assessing scaffold aesthetic properties. With this dynamic 3D bioprinting strategy, complex geometries with robust internal structures can be easily modulated by varying the print ratio of nondegradable to sacrificial strands. The versatility of this hybrid printing fabrication platform can inspire the design of future multimaterial regenerative implants.     

Capturing Complex Protein Gradients on Biomimetic Hydrogels for Cell‐Based Assays

A versatile strategy to rapidly immobilize complex gradients of virtually any desired protein on soft poly(ethylene glycol) (PEG) hydrogel surfaces that are reminiscent of natural extracellular matrices (ECM) is reported. A microfluidic chip is used to generate steady‐state gradients of biotinylated or Fc‐tagged fusion proteins that are captured and bound to the surface in less than 5 min by NeutrAvidin or ProteinA, displayed on the surface. The selectivity and orthogonality of the binding schemes enables the formation of parallel and orthogonal overlapping gradients of multiple proteins, which is not possible on conventional cell culture substrates. After patterning, the hydrogels are released from the microfluidic chip and used for cell culture. This novel platform is validated by conducting single‐cell migration experiments using time‐lapse microscopy. The orientation of cell migration, as well as the migration rate of primary human fibroblasts, depends on the concentration of an immobilized fibronectin fragment. This technique can be readily applied to other proteins to address a wealth of biological questions with different cell types.     

Novel PEGylated Nanoassemblies Made of Self‐Assembled Squalenoyl Nucleoside Analogues

This study describes a new simple method to obtain high loading of anticancer or antiviral nucleoside analogues into “stealth” poly(ethylene glycol) (PEG)‐coated nanoassemblies. These nanodevices are obtained by co‐nanoprecipitation in water of (i) squalenoyl prodrugs obtained by the bioconjugation of the natural lipid squalene with either the anticancer drug gemcitabine (Gem‐Sq) or the antiviral drug deoxycytidine (ddC‐Sq) with (ii) a PEG derivative of either cholesterol (Chol‐PEG) or squalene (Sq‐PEG). It was found that both PEG derivatives (Chol‐PEG or Sq‐PEG) were efficiently incorporated in the resulting composite nanoassemblies (CNAs), as shown by radioactivity studies, Zeta potential determination, and size measurements. Optimal compositions were defined for each PEG derivative to ensure the best stability in water and in buffer solutions. X‐ray diffraction and electron microscopy investigations revealed that depending on the structure of the squalenoyl nucleoside analogue used (Gem‐Sq or ddC‐Sq), these nanoassemblies might be toroids or cubosomes. Following PEGylation, the Gem‐Sq nanoassemblies displayed superior in vitro anticancer activity on gemcitabine‐resistant leukemia L1210 10K cells than either their non‐PEGylated counterparts or gemcitabine alone.     

Supercritical CO2: A Clean and Low Temperature Approach to Blending PDLLA and PEG

The unique combination of the gas like viscosity and liquid like density of supercritical CO₂ (scCO₂) is exploited to blend poly(D,L‐lactic acid) (P_DLLA) and poly(ethylene glycol) (PEG) at near ambient temperatures. This novel process lowers the polymer blend viscosity and also permits incorporation of thermally and solvent labile protein based drugs. A series of blends are prepared with agitation in scCO₂. Differential scanning calorimetry (DSC) data shows that miscible blends can be produced at moderate temperatures. A surprising region of miscibility is revealed between 8 and 25%w/w PEG. The properties of this miscible region are probed with high pressure parallel plate rheological studies, showing that the viscosity in scCO₂ is directly related to the miscibility. Using the particles from gas saturated solutions (PGSS) method, microparticles of these P_DLLA/PEG blends are produced using scCO₂ and it is determined that the yields obtained are proportional to the miscibility of the polymers. Thus scCO₂ provides a unique route to low temperature, solvent free processing that accesses a window of miscibility that has not previously been observed. Finally, DSC analyses of these sprayed microparticles confirm the presence of the same high miscibility region observed in the bulk samples prepared under supercritical conditions.     

Affinity‐Based Protein Surface Pattern Formation by Ligand Self‐Selection from Mixed Protein Solutions

Photolithographically prepared surface patterns of two affinity ligands (biotin and chloroalkane) specific for two proteins (streptavidin and HaloTag, respectively) are used to spontaneously form high‐fidelity surface patterns of the two proteins from their mixed solution. High affinity protein‐surface self‐selection onto patterned ligands on surfaces exhibiting low non‐specific adsorption rapidly yields the patterned protein surfaces. Fluorescence images after protein immobilization show high specificity of the target proteins to their respective surface patterned ligands. Time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) imaging further supports the chemical specificity of streptavidin and HaloTag for their surface patterned ligands from mixed protein solutions. However, ToF‐SIMS did detect some non‐specific adsorption of bovine serum albumin, a masking protein present in excess in the adsorbing solutions, on the patterned surfaces. Protein amino acid composition, surface coverage, density, and orientation are important parameters that determine the relative ToF‐SIMS fragmentation pattern yields. ToF‐SIMS amino acid‐derived ion fragment yields summed to produce surface images can reliably determine which patterned surface regions contain bound proteins, but do not readily discriminate between different co‐planar protein regions. Principal component analysis (PCA) of these ToF‐SIMS data, however, improves discrimination of ions specific to each protein, facilitating surface protein pattern identification and image contrast.     

Autonomic Self‐Healing of PEDOT:PSS Achieved Via Polyethylene Glycol Addition

Self‐healing electronic materials are of primary interest for bioelectronics and sustainable electronics. In this work, autonomic self‐healing of films obtained from mixtures of the conducting polymer poly(3,4‐ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) and polyethylene glycol (PEG) is reported. The presence of PEG in PEDOT:PSS films decreases the elastic modulus and increases the elongation at break, thus leading to a softer material with enhanced self‐healing characteristics. In situ imaging of the cutting/healing process shows that the healing mechanism is likely due to flowing back of the material to the damaged area right after the cutting.     

Amphiphilic Poly(Amino Acid) Nanoparticles Induce Size‐Dependent Dendritic Cell Maturation

Size‐regulated amphiphilic poly(amino acid) nanoparticles (NPs) composed of poly(γ‐glutamic acid) (γ‐PGA) and the hydrophobic amino acid derivative, L ‐phenylalanine ethyl ester (Phe) are prepared to evaluate the effects of particle size on dendritic cell (DC) uptake of NPs and their immune stimulatory activities as delivery carriers and adjuvants. The size of the Phe‐conjugated γ‐PGA NPs (γ‐PGA–Phe NPs) is easily controlled by regulating the aggregated γ‐PGA–Phe numbers. Each of the differently sized γ‐PGA–Phe NPs could efficiently encapsulate ovalbumin (OVA), and the amount of encapsulated OVA per milligram of NPs is almost the same despite the differences in size. The DC uptake of small NPs is lower than for the larger NPs, but the effect of DC activation by NPs is high in the small sizes. The DC activation is significantly affected by the size of the NPs, which suggests that not only the uptake process of the NPs, but also the surface interactions between the NPs and DCs, is important for the induction of DC maturation. The precisely size‐controllable γ‐PGA–Phe NPs have significant potential as an antigen carrier and vaccine adjuvant. These results should provide guidelines for adjuvant design in the development of an effective vaccine.     

The Interplay of Modulus,Strength, and Ductility in Adhesive Design Using Biomimetic Polymer Chemistry

High‐performance adhesives require mechanical properties tuned to demands of the surroundings. A mismatch in stiffness between substrate and adhesive leads to stress concentrations and fracture when the bonding is subjected to mechanical load. Balancing material strength versus ductility, as well as considering the relationship between adhesive modulus and substrate modulus, creates stronger joints. However, a detailed understanding of how these properties interplay is lacking. Here, a biomimetic terpolymer is altered systematically to identify regions of optimal bonding. Mechanical properties of these terpolymers are tailored by controlling the amount of a methyl methacrylate stiff monomer versus a similar monomer containing flexible poly(ethylene glycol) chains. Dopamine methacrylamide, the cross‐linking monomer, is a catechol moiety analogous to 3,4‐dihydroxyphenylalanine, a key component in the adhesive proteins of marine mussels. Bulk adhesion of this family of terpolymers is tested on metal and plastic substrates. Incorporating higher amounts of poly(ethylene glycol) into the terpolymer introduces flexibility and ductility. By taking a systematic approach to polymer design, the region in which material strength and ductility are balanced in relation to the substrate modulus is found, thereby yielding the most robust joints.     

Colorimetric Logic Gates Based on Poly(2‐alkyl‐2‐oxazoline)‐Coated Gold Nanoparticles

A straightforward end‐capping strategy is applied to synthesize xanthate‐functional poly(2‐alkyl‐2‐oxazoline)s (PAOx) that enable gold nanoparticle functionalization by a direct “grafting to” approach with citrate‐stabilized gold nanoparticles (AuNPs). Owing to the presence of remaining citrate groups, the obtained PAOx@AuNPs exhibit dual stabilization by repulsive electrostatic and steric interactions giving access to water soluble molecular AND logic gates, wherein environmental temperature and ionic strength constitute the input signals, and the solution color the output signal. The temperature input value could be tuned by variation of the PAOx polymer composition, from 22 °C for poly(2‐ⁿpropyl‐2‐oxazoline)@AuNPs to 85 °C for poly(2‐ethyl‐2‐oxazoline)@AuNPs. Besides, advancing the fascinating field of molecular logic gates, the present research offers a facile strategy for the synthesis of PAOx@AuNPs of interest in fields spanning nanotechnology and biomedical sciences. In addition, the functionalization of PAOx with xanthate offers straightforward access to thiol‐functional PAOx of high interest in polymer science.     

Enabling Stable Cycling of 4.2 V High‐Voltage All‐Solid‐State Batteries with PEO‐Based Solid Electrolyte

Poly(ethylene oxide) (PEO)‐based solid electrolytes are expected to be exploited in solid‐state batteries with high safety. Its narrow electrochemical window, however, limits the potential for high voltage and high energy density applications. Herein the electrochemical oxidation behavior of PEO and the failure mechanisms of LiCoO₂‐PEO solid‐state batteries are studied. It is found that although for pure PEO it starts to oxidize at a voltage of above 3.9 V versus Li/Li⁺, the decomposition products have appropriate Li⁺ conductivity that unexpectedly form a relatively stable cathode electrolyte interphase (CEI) layer at the PEO and electrode interface. The performance degradation of the LiCoO₂‐PEO battery originates from the strong oxidizing ability of LiCoO₂ after delithiation at high voltages, which accelerates the decomposition of PEO and drives the self‐oxygen‐release of LiCoO₂, leading to the unceasing growth of CEI and the destruction of the LiCoO₂ surface. When LiCoO₂ is well coated or a stable cathode LiMn_0.7Fe_0.3PO₄ is used, a substantially improved electrochemical performance can be achieved, with 88.6% capacity retention after 50 cycles for Li_1.4Al_0.4Ti_1.6(PO₄)₃ coated LiCoO₂ and 90.3% capacity retention after 100 cycles for LiMn_0.7Fe_0.3PO₄. The results suggest that, when paired with stable cathodes, the PEO‐based solid polymer electrolytes could be compatible with high voltage operation.     

Single‐Step Deposition of Au‐ and Pt‐Nanoparticle‐Functionalized Tungsten Oxide Nanoneedles Synthesized Via Aerosol‐Assisted CVD,and Used for Fabrication of Selective Gas Microsensor Arrays

Tungsten oxide nanostructures functionalized with gold or platinum NPs are synthesized and integrated, using a single‐step method via aerosol‐assisted chemical vapour deposition, onto micro‐electromechanical system (MEMS)‐based gas‐sensor platforms. This co‐deposition method is demonstrated to be an effective route to incorporate metal nanoparticles (NP) or combinations of metal NPs into nanostructured materials, resulting in an attractive way of tuning functionality in metal oxides (MOX). The results show variations in electronic and sensing properties of tungsten oxide according to the metal NPs introduced, which are used to discriminate effectively analytes (C₂H₅OH, H₂, and CO) that are present in proton‐exchange fuel cells. Improved sensing characteristics, in particular to H₂, are observed at 250 °C with Pt‐functionalized tungsten oxide films, whereas non‐functionalized tungsten oxide films show responses to low concentrations of CO at low temperatures. Differences in the sensing characteristics of these films are attributed to the different reactivities of metal NPs (Au and Pt), and to the degree of electronic interaction at the MOX/metal NP interface. The method presented in this work has advantages over other methods of integrating nanomaterials and devices, of having fewer processing steps, relatively low processing temperature, and no requirement for substrate pre‐treatment.     

Red‐ to NIR‐Emitting,BODIPY‐Based,K+‐Selective Fluoroionophores and Sensing Materials

Optical sensing materials for the selective measurement of potassium ions (K⁺) in water are presented. The indicator dyes are based on an aza‐crown ether as a receptor and borondipyrromethenes (BODIPY) dyes as fluorophores. Fluorescence enhancement is caused by the reduction of photoinduced electron transfer (PET) upon complexation with K⁺ ions. The family of new indicators possesses tuneable optical properties (green to red excitation, red to NIR emission) and PET efficiencies. They exhibit high brightness with quantum yields between 0.20 and 0.47 in the “on” state and a molar absorption coefficient between 30 000 and 290 000 m ^?1 cm^?1. The new indicator dyes are immobilized in biocompatible hydrogel matrices to obtain stable nonleaching and fast responding (t₉₀ ≈ 10 s) sensing materials for continuous measurements of potassium. They are realized in various formats such as planar optodes, fiber‐optic sensors, and water‐dispersible polymer‐based nanoparticles. Apart from fluorescence intensity measurements, self‐referenced read‐out of fluorescence decay time is demonstrated. All sensor materials display a high K⁺/Na⁺ selectivity and are not influenced by pH within the physiologically relevant range. Practical applicability of the materials is emphasized by application of a fiber‐optic sensor to quantification of K⁺ in serum, which shows excellent correlation with the reference measurements.