Microgel Films Research Articles

PNIPAM microgel coatings of LiF crystal radiation detectors

Thin films of poly(N-isopropylacrylamide) (PNIPAM) microgels have recently attracted significant attention as promising candidates for creating switchable interfaces in biomedical and biotechnological applications. In this study, microgel films are proposed as smart coatings for photoluminescent solid-state radiation detectors based on lithium fluoride (LiF). Understanding the impact of the solid substrate is crucial for customising and refining microgel coatings for specific applications. To investigate the effects of surface quality, microgel size, and particle concentration on the properties of microgel films, PNIPAM microgels were spin-coated onto LiF crystal surfaces and characterised through wettability measurements, UV-Vis-NIR spectrophotometry, and Atomic Force Microscopy. This approach enabled effective control over the optical and morphological properties of the films, paving the way for the development of hybrid and potentially biocompatible radiation detectors using PNIPAM microgel films.

Influence of a Solid Surface on PNIPAM Microgel Films.

Stimuli-responsive microgels have attracted great interest in recent years as building blocks for fabricating smart surfaces with many technological applications. In particular, PNIPAM microgels are promising candidates for creating thermo-responsive scaffolds to control cell growth and detachment via temperature stimuli. In this framework, understanding the influence of the solid substrate is critical for tailoring microgel coatings to specific applications. The surface modification of the substrate is a winning strategy used to manage microgel-substrate interactions. To control the spreading of microgel particles on a solid surface, glass substrates are coated with a PEI or an APTES layer to improve surface hydrophobicity and add positive charges on the interface. A systematic investigation of PNIPAM microgels spin-coated through a double-step deposition protocol on pristine glass and on functionalised glasses was performed by combining wettability measurements and Atomic Force Microscopy. The greater flattening of microgel particles on less hydrophilic substrates can be explained as a consequence of the reduced shielding of the water-substrate interactions that favors electrostatic interactions between microgels and the substrate. This approach allows the yielding of effective control on microgel coatings that will help to unlock new possibilities for their application in biomedical devices, sensors, or responsive surfaces.

Preparation of Temperature-Responsive Films Based on PNVCL Microgel with Varying Sizes and Cross-Linking Degrees for Cell Harvesting.

This work reports preparing thermal responsive poly (N-isovinylcaprolactam) (PNVCL) microgel based films for cell growth and detachment. PNVCL microgels of hydrated size ranging from 386 to 815nm (25°C) and different crosslinking degree are prepared. The PNVCL microgels can be rapidly and massively deposited on glass by spin coating method. Atomic force microscopy (AFM) and water contact angle (WCA) are used to study the influence of crosslinking degree and particle size on the surface morphology, stability, and hydrophilicity of PNVCL microgel film. The cell activity of the desorbed cells is quantitatively characterized employing human normal lung epithelial cells (BEAS-2B). The results show that BEAS-2B cells can be desorbed quickly from the film in 30 min, and the optical density (OD) value of desorbed cells incubated after 3 d increases by approximately 52% compared to the control group. This study broadens the selection of temperature-sensitive film for cell harvesting, and provides a new tool for the quantitative characterization of desorbed cells.

Water-borne synthesis of multi-responsive and biodegradable chitosan-crosslinked microgels: Towards self-assembled films with adaptable properties

The present study aims in the synthesis of new biodegradable stimuli-responsive microgels with controllable microstructure and with the ability to form cohesive films. Such self-assembled films by water evaporation at ambient conditions without any chemicals but just physical entanglements between soft colloid shell, present adaptable mechanical, adhesive and mechano-electrical properties. For that, oligo(ethylene glycol)-based stimuli-responsive microgels have been synthesized using biodegradable chitosan-methacrylates (Chi-MAs) with different degree of substitution (DS) as unique cross-linking agents by precipitation polymerization in water, for the first time. In all the cases, the microgels present thermo-responsiveness with hysteresis between heating and cooling cycles. However, this behavior is tuned and controlled using different types and amounts of Chi-MAs. In addition, the type of Chi-MA used can control microgels' microstructure as well as their enzymatic biodegradation. In addition, spontaneous cohesive films formation from colloidal aqueous dispersion with sol-gel transition is demonstrated. The films present tunable mechanical and adhesive properties through microgels' microstructure and enhanced mechano-electrical properties triggered by simple finger pressure (10–15 N). As self-supported films are able to encapsulate different types of active molecules, this study paves the way for suitable self-assembled microgel films for skincare applications as transdermal delivery systems.

Tough and Transparent Photonic Hydrogel Nanocomposites for Display, Sensing, and Actuation Applications

Thermosensitive hydrogels with periodic dielectric structures displaying tunable structural color by temperature stimuli have attracted much research interest recently. However, reported thermosensitive photonic hydrogels either using the poly(N-isopropylacrylamide) (PNIPAM) bulk hydrogel as the responsive matrix or using PNIPAM microgels as the photonic building blocks have poor mechanical strength. Moreover, the expensive and time-consuming preparation process also limits their further application. In this work, a different strategy for preparing PNIPAM-based photonic hydrogel nanocomposite films with strong mechanical strength is proposed by incorporating a PNIPAM microgel film with the polyacrylamide (PAM) hydrogel. The preparation process is simple but efficient, and the obtained nanocomposite films have tunable mechanical strength by changing the crosslinking degree of the PAM hydrogels. More interestingly, the structural color of the nanocomposite films can be retained up to 80 °C (at least), much higher than those of previously reported PNIPAM-based photonic materials. In addition to being thermochromic, the film is sensitive to humidity, and the structural color-changing process is similar to the molting process of cicadas. Furthermore, the nanocomposite films have synchronous shape deformations and color changes and can be used as color-tunable soft actuators. The microgel film-capped photonic hydrogels provide a new strategy for the preparation of thermoresponsive photonic hydrogels and structural color-tunable actuators.

Macroscopic Supramolecular Assembly of Rigid Building Blocks Facilitated by Layer-By-Layer Assembled Microgel Film

Macroscopic supramolecular assembly (MSA) of building blocks larger than 1 μm provides new methodology for fabrication of functional supramolecular materials and a platform for mechanism investigation of interfacial phenomena. Most reports on MSA are restricted to soft hydrogels, and supramolecular groups can be directly integrated into a hydrogel matrix to generate sufficient attraction for maintaining macroscopic assemblies. For non-hydrogel stiff building blocks, two layer-by-layer modification processes consisting of flexible spacing coating and additional interacting groups are necessary to enable MSA, which is laborious and time-consuming. Approaches for highly efficient MSA based on flexible spacing coating are desired. In this work, MSA of polydimethylsiloxane (PDMS) building blocks is demonstrated by inducing microgel films that serve as both flexible spacing coating and surface functional groups, thus avoiding a two-step LbL modification process. By the varying bilayer number of microgel films, the MSA probability of modified PDMS increases from 54% at 3 bilayers to 100% at 6 bilayers. Control experiments and in situ force measurement strongly support the obtained MSA results and verify the dominant role of the microgel film as a flexible spacing coating and a supramolecularly interactive layer in achieving MSA. Moreover, the underlying mechanism is interpreted as low Young's modulus microgel films rendering surface groups highly mobile to enhance the multivalent interfacial binding. Taken together, this work has demonstrated the feasibility of MSA of rigid building blocks assisted by microgel films as flexible spacing coating and supramolecularly interactive layer simultaneously, which may extend the application fields of microgel materials to interfacial adhesion and advanced manufacturing with MSA methodology.

Microgels in Tandem with Enzymes: Tuning Adsorption of a pH‐ and Thermoresponsive Microgel for Improved Design of Enzymatic Biosensors

AbstractThe benefits of stimuli‐responsiveness of microgels for surface modification and further engineering of microgel‐enzyme biosensor constructs are highlighted. Accordingly, the adsorption behavior of the pH‐ and temperature‐sensitive poly(N‐isopropylacrylamide‐co‐N‐(3‐dimethylaminopropyl)methacrylamide) microgel (P(NIPAM‐co‐DMAPMA) microgel) is examined by means of atomic force microscopy (AFM) and quartz‐crystal microbalance with dissipation monitoring (QCM‐D). An enhanced adsorption of the microgel onto relatively hydrophobic surfaces is observed at elevated pH and temperature as manifested by a high surface coverage and a large adsorbed mass. This is a consequence of pronounced hydrophobization of the microgel as revealed by means of dynamic light scattering (DLS) and turbidimetry (cloud points). The subsequent electrostatic loading of the surface‐bound microgel with enzymes is examined by means of QCM‐D and demonstrates a highly‐capacious integration of biomolecules into the microgel films. Finally, the biosensor responses of the microgel‐enzyme films fabricated onto screen‐printed graphite electrodes are assessed to demonstrate a biorelated application. Thus, a comprehensive conceptual understanding is attained on the key points: (1) how the stimuli‐responsive properties of the microgel correlate with its amount deposited onto the surface, (2) what determines the highly‐capacious loading of the surface‐bound microgel with the enzymes, and ultimately (3) how the tandem of the stimuli‐sensitive microgels and enzymes can be used for easy engineering of biosensor systems.

Electrochemically Initiated Synthesis of Polyacrylamide Microgels and Core-shell Particles.

Herein, we developed a simple procedure for synthesizing micrometer-sized microgel particles as a suspension in an aqueous solution and thin films deposited as shells on different inorganic cores. A sufficiently high constant potential was applied to the working electrode to commence the initiator decomposition that resulted in gelation. Under hydrodynamic conditions, this initiation allowed preparing different morphology microgels at room temperature. Importantly, neither heating nor UV-light illumination was needed to initiate the polymerization. Moreover, thin films of the cross-linked gel were anchored on different core substrates, including silica and magnetic nanoparticles. Scanning electron microscopy and transmission electron microscopy imaging confirmed the microgel particles’ and films’ irregular shape and porous structure. Energy-dispersive X-ray spectroscopy indicated that the core coating with the microgel film was successful. Dynamic light scattering measured the micrometer size of gel particles with different combinations of acrylic monomers. Thermogravimetric analysis and the first-derivative thermogravimetric analysis revealed that the microgels’ thermal stability of different compositions was different. Fourier-transform infrared and 13C NMR spectroscopy showed successful copolymerization of the main, functional, and cross-linking monomers.

Analysis of thermo-plasmonic lab-on-fiber probes in liquid environments

Lab-on-fiber (LOF) optrodes are recently emerging not only as valid platforms for biosensing, but also as promising light-controlled actuators in drug-delivery, optical trapping and thermo-ablation systems. In this regard, the thermo-plasmonic effect has been recognized as an intriguing tool for conferring to the optical fiber the capability of interacting with the external environment through the fine control of local overheating actuated by light in the range of few mW. However, the evaluation of the thermo-plasmonic overheating on small areas such as that of a standard single mode fiber tip is not trivial, especially in liquid solutions, where these probes typically operate. Here we demonstrate that by functionalizing the metallic nanostructure of LOF devices with a thermoresponsive smart materials, it is possible to measure the light-induced overheating on the fiber tip. Specifically, we monitored the plasmonic resonance wavelength shift induced by the temperature-dependent swelling dynamics of different microgel films deposited on the nanostructure. We find a local overheating of about 8 °C mW−1, i.e. also in line with our theoretical predictions based on numerical simulations. Our results demonstrate that the proposed approach is a valid methodology for the direct and continuous monitoring of the temperature changes in LOF devices induced by the input optical power in liquid environment. Our findings lay the basis for the analysis of thermo-plasmonic optical fiber probes exploitable in many applications, especially for the life science sector.

Micro-gel thin film molecularly imprinted polymer coating for extraction of organophosphorus pesticides from water and beverage samples

Molecularly imprinted polymers (MIPs) have become an important class of materials for selective and efficient adsorption of target analytes. Despite versatility of MIPs for fabrication in numerous formats, these materials have been primarily reported as solid phase extraction packing materials. An effective thin film MIP prepared on stainless steel substrate is reported here for high throughput enrichment of organophosphorus pesticides (OPPs) from water and beverage samples followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The key factors controlling performance as well as best practices for optimized fabrication of thin film MIPs are presented. A pseudo-phase diagram is introduced to evaluate and predict the effect of the ratio of porogen (solvent, 1-octanol) volume to relative crosslinker mass on the desired polymer features (i.e., porosity, surface area, capacity, and selectivity). At low porogen ratios, a macroporous polymer with insignificant selectivity is formed, whereas at high porogen ratios a micro-gel polymer with superior selectivity towards targets is obtained. The porosity and morphology determined with nitrogen adsorption and scanning electron microscopy were attributed to specific regions in the pseudo-phase diagram. Other factors influencing selectivity and stability of the polymer, such as type of the template and its ratios with monomer (methacrylic acid) and crosslinker (ethylene glycol dimethacrylate) were optimized. The prepared thin film MIPs were characterized using adsorption isotherms and adsorption kinetics, and evaluated for matrix effects (high humic acid content) and cross-reactivity in presence of other pesticides and pharmaceuticals. The optimized method provided limits of quantitation (LOQs) ranged from 0.002 to 0.02 ng mL−1 in water and from 0.095 to 0.48 ng g−1 in apple juice. Regarding inter-device variability (CV∼10% without normalization), excellent linearity (R2 > 0.99), satisfactory accuracies (90–110%) and precisions (<15%) were obtained.

Spontaneously Self-Assembled Microgel Film as Co-Delivery System for Skincare Applications.

Nowadays, the design of innovative delivery systems is driving new product developments in the field of skincare. In this regard, serving as potential candidates for on-demand drug delivery and fulfilling advanced mechanical and optical properties together with surface protection, spontaneously self-assembled microgel films can be proposed as ideal smart skincare systems. Currently, the high encapsulation of more than one drug simultaneously in a film is a very challenging task. Herein, different ratios (1:1, 3:1, 9:1) of different mixtures of hydrophilic/hydrophobic UVA/UVB-absorbers working together in synergy and used for skin protection were encapsulated efficiently into spontaneously self-assembled microgel films. In addition, in vitro release profiles show a controlled release of the different active molecules regulated by the pH and temperature of the medium. The analysis of the release mechanisms by the Peppas–Sahlin model indicated a superposition of diffusion-controlled and swelling-controlled releases. Finally, the distribution of active molecule mixtures into the film was studied by confocal Raman microscopy imaging corroborating the release profiles obtained.

Selective Adhesion and Switchable Release of Breast Cancer Cells via Hyaluronic Acid Functionalized Dual Stimuli-Responsive Microgel Films.

The detection of tumor cells from liquid biopsy samples is of critical importance for early cancer diagnosis, malignancy assessment, and treatment. In this work, coatings of hyaluronic acid (HA)-functionalized dual-stimuli responsive poly(N-isopropylacrylamide) (PNIPAM) microgels are used to study the specificity of breast cancer cell binding and to assess cell friendly release mechanisms for further diagnostic procedures. The microgels are established by straightforward precipitation polymerization with amine bearing comonomers and postfunctionalization with a UV-labile linker that covalently binds HA to the microgel network. Well-defined microgel coatings for cell binding are established via simple physisorption and annealing. The HA-presenting PNIPAM microgel films are shown to specifically adhere CD44 expressing breast cancer cell lines (MDA-MB-231 and MCF-7), where an increase in adhesion correlates with higher CD44 expression and HA functionalization. Upon cooling below the lower critical solution temperature of PNIPAM microgels, the cells could be released; however, 10-30% of the cells still remained on the surface even after prolonged cooling and mild mechanical agitation. A complete cell release is achieved after applying the light stimulus by short UV treatment cleaving HA units from the microgels. Owing to the comparatively straightforward preparation procedures, such dual-responsive microgel films could be considered for the effective capture, release, and diagnostics of tumor cells.

Programmable Color in a Free-Standing Photonic Microgel Film with Ultra-Fast Response.

In this work, a free-standing microgel film with programmable and angle-independent structural color is prepared via a simple but effective method. Dried poly(styrene-N-isopropylacrylamide-acrylic acid) (pStNIPAAmAA) microgels were stabilized by inter-microgel crosslinking, and thus, only microgels were used to build the optical hydrogel. The free-standing microgel film displayed tunable structural color by the swelling/deswelling of the microgels under external stimuli, such as temperature, pH, ionic strength, and organic solvent. Moreover, the structural color of the film is angle-independent for the disordered microgel arrays. It is worth noting that programmable color stripes which have the panther chameleon's ability to change skin color are successfully fabricated by patterning microgels with different thermoresponsivities. More importantly, the microgel film has an ultrafast response to temperature (1.41 s from 20 to 40 °C) and pH (2.24 s from pH 8.3 to pH 2.0), much faster than that of most optical materials reported in previous studies.

Fast self-assembled microfibrillated cellulose@MXene film with high-performance energy storage and superior mechanical strength

The trade-off between the electrochemical performance and mechanical strength is still a challenge for Ti3C2Tx free-standing electrode. Herein, a facile approach was proposed to fabricate a Microfibrillated cellulose@Ti3C2Tx (MFC@Ti3C2Tx) self-assembled microgel film by means of hydrogen bonding linkage. Benefiting from the rich hydroxyl groups on the MFC, the Ti3C2Tx nanosheets coated on the MFC in a time scale of minutes (within 1 min) instead of hours. The ultralong 1D frame of MFC effectively mitigated the re-aggregation of Ti3C2Tx nanosheet. The fluffy MFC@Ti3C2Tx film structure and the constructed 1D/2D conducting Ti3C2Tx pathways in horizontal and vertical directions endowed the fast ion transport of the electrolytes and the improved accessibility to the Ti3C2Tx surface. As a result, the freestanding MFC@Ti3C2Tx microgel film delivered a high specific capacitance of 451F/g. And the rate performance was increased to 71% from the 64% of that of pristine Ti3C2Tx film. Furthermore, the tensile strength of MFC@Ti3C2Tx film was also promoted to 46.3 MPa, 3 folds of that of the pristine Ti3C2Tx film, due to the high strength of MFC and the hydrogen bonding effect.

Microgel structure-driven linear and non-linear mechanical properties of self-assembled microgel films

Soft self-supported cohesive films were formed by self-assembly of pH- and thermo-responsive P(MEO2MA-co-OEGMA-co-MAA) microgels without any preparation and/or post-treatments. Linear and non-linear mechanical properties of those films were characterized respectively by dynamic mechanical measurements at low strain and uniaxial extensional tests at high deformation. A relationship between the microstructure of microgels and the mechanical strength of microgel-based films was successfully established. Compared to microgels crosslinked with Oligo(ethylene glycol) diacrylate (OEGDA), microgels with N,N-methylenebisacrylamide (MBA) demonstrate a less crosslinked structure but especially a looser shell which enables the particles to better interpenetrate between one another and resist to higher deformation. Novel films were also designed by controlled mixing microgels and the synthesis side-product, namely water-soluble polymer, WSP, in a ratio with WSP content till 100 %. Those films demonstrated promising mechanical properties due to the structural characteristics of the later. The later act as a lever to tune the elastic modulus of films without diminishing their resistance at strain thanks to its high molar mass and crosslinked structure revealed by Steric Exclusion Chromatography (SEC) measurements.

Ultrasonic Microplotting of Microgel Bioinks.

Material scaffolds that mimic the structure, function, and bioactivity of native biological tissues are in constant development. Recently, material scaffolds composed of microgel particles have shown promise for applications ranging from bone regeneration to spheroid cell growth. Previous studies with poly N-isopropylacrylamide microgel scaffolds utilized a layer-by-layer (LBL) technique where individual, uniform microgel layers are built on top of each other resulting in a multilayer scaffold. However, this technique is limited in its applications due to the inability to control microscale deposition or patterning of multiple particle types within a microgel layer. In this study, an ultrasonic microplotting technique is used to address the limitations of LBL fabrication to create patterned microgel films. Printing parameters, such as bioink formulation, surface contact angle, and print head diameter, are optimized to identify the ideal parameters needed to successfully print microgel films. It was found that bioinks composed of 2 mg/mL of microgels and 20% polyethylene glycol by volume (v/v), on bovine serum albumin-coated glass, with a print head diameter of 50 μm resulted in the highest quality prints. Patterned films were created with a maximum resolution of 50 μm with the potential for finer resolutions to be achieved with alternative bioink compositions and printing parameters. Overall, ultrasonic microplotting can be used to create more complex microgel films than is possible with LBL techniques and offers the possibility of greater printing resolution in 3D with further technology development.

Adhesion of Epithelial Cells to PNIPAm Treated Surfaces for Temperature-Controlled Cell-Sheet Harvesting.

Stimuli responsive polymer coatings are a common motive for designing surfaces for cell biological applications. In the present study, we have characterized temperature dependent adhesive properties of poly(N-isopropylacrylamide) (PNIPAm) microgel coated surfaces (PMS) using various atomic force microscopy based approaches. We imaged and quantified the material properties of PMS upon a temperature switch using quantitative AFM imaging but also employed single-cell force spectroscopy (SCFS) before and after decreasing the temperature to assess the forces and work of initial adhesion between cells and PMS. We performed a detailed analysis of steps in the force–distance curves. Finally, we applied colloid probe atomic force microscopy (CP-AFM) to analyze the adhesive properties of two major components of the extracellular matrix to PMS under temperature control, namely collagen I and fibronectin. In combination with confocal imaging, we could show that these two ECM components differ in their detachment properties from PNIPAm microgel films upon cell harvesting, and thus gained a deeper understanding of cell-sheet maturation and harvesting process and the involved partial ECM dissolution.

A New and Straightforward Strategy to Prepare an Optical Hydrogel Film with Dynamic Structural Colors

A straightforward strategy is first proposed to prepare an optical hydrogel film with dynamic structural colors. This was achieved by entrapping a dry thermoresponsive microgel film in a thermoresp...

Antibacterial coatings based on microgels containing quaternary ammonium ions: Modification with polymeric sugars for improved cytocompatibility

The availability of biocompatible, anti-bacterial coatings is of extreme importance for the development of biomedical devices. However, it has proven to be difficult to achieve both biocompatibility and bactericidal properties simultaneously. In the present work, as a novel, alternative approach, a quaternary ammonium salt-based poly(N-isopropylacrylamide) (QAS-PNIPAM) microgel was used both as the bactericidal agent and as an anchor system for the attachment of a cyto-compatibility-enhancing component. QAS-PNIPAM microgels were first prepared as thin films on silicon wafer. The QAS component of the film, as well as having strong inherent bactericidal properties, also provided binding sites for attachment of a glycopolymer containing sulfonate groups via attractive electrostatic interactions. It was shown that introduction of the sugar units improved the cytocompatibility of the microgel film without compromising its bactericidal efficacy. It is proposed that such microgel coatings may serve more generally as intermediates for the attachment of biofunctional components to biomaterial surfaces.

Poly(N-isopropylacrylamide) based thin microgel films for use in cell culture applications

Poly(N-isopropylacrylamide) (PNIPAm) is widely used to fabricate cell sheet surfaces for cell culturing, however copolymer and interpenetrated polymer networks based on PNIPAm have been rarely explored in the context of tissue engineering. Many complex and expensive techniques have been employed to produce PNIPAm-based films for cell culturing. Among them, spin coating has demonstrated to be a rapid fabrication process of thin layers with high reproducibility and uniformity. In this study, we introduce an innovative approach to produce anchored smart thin films both thermo- and electro-responsive, with the aim to integrate them in electronic devices and better control or mimic different environments for cells in vitro. Thin films were obtained by spin coating of colloidal solutions made by PNIPAm and PAAc nanogels. Anchoring the films to the substrates was obtained through heat treatment in the presence of dithiol molecules. From analyses carried out with AFM and XPS, the final samples exhibited a flat morphology and high stability to water washing. Viability tests with cells were finally carried out to demonstrate that this approach may represent a promising route to integrate those hydrogels films in electronic platforms for cell culture applications.