Large numbers of papers which include studies on hydrogels use SEM images to analyze pore sizes, often demonstrating so-called micropores of few to tens of micrometers in size. Commonly, hydrogels are lyophilized, which often involves freezing under insufficiently controlled conditions. Considering experience from cryo-electron microscopy and the behavior of water during freezing, the obvious question arises: Was the freezing process fast enough to avoid formation of ice crystals? If not, freeze drying will lead to phase separation and formation of voids and pores. Here we show, using pNIPAM hydrogels as example, that freezing can indeed produce micropores. We propose an alternative, chemical preparation for hydrogels based on infiltration with tannic acid allowing ultrastructural analysis without creating artificial micropores. To study the hydrogel samples’ interior, they were either fractured or embedded into an epoxide resin for sectioning by ultramicrotomy. Analysis of hydrogels prepared in a controlled, chemical way revealed no micropores, but pores in the range of 20-100 nanometers for a pNIPAM formulation with high water content. Two-photon printed microstructures with intrinsically lower water content could also be stabilized by the chemical protocol and sections showed corresponding nanopores. Preparation with tannic acid thus provides a convenient route to fast and artefact-minimized screening and benchmarking of structured hydrogels.
Organisms produce diverse optical systems via biomineralization of purines and pteridines, forming high-refractive-index crystals that enable structural coloration, visual image formation and photosynthesis enhancement. Distinct from conventional inorganic biomineralization, these biogenic organic crystals and their hierarchical assemblies are highly susceptible to conventional electron microscopy sample treatments, which cause dehydration, structural distortion and other artifacts formation. Cryogenic scanning electron microscopy (cryo-SEM) combined with high-pressure freezing effectively preserves native hydrated states and vitrifies intracellular water, avoiding common artifacts and enabling high-resolution visualization (∼ 10 nm) of delicate photonic structures. This review summarizes recent cryo-SEM investigations on guanine, xanthine, isoxanthopterin and 7,8-dihydroxanthopterin across a wide range of organisms. We elaborate their crystal packing modes, anisotropic optical properties, and structure–function correlations in biogenic optical systems. We also discuss developmental crystallization pathways of these organic crystals, revealing how organisms regulate nucleation, growth and assembly to design and fabricate targeted optical systems for specialized functions. This work demonstrates that cryo-SEM is a powerful tool for exploring organic biomineralization, and provides fundamental insights for developing bioinspired optically functional artificial materials.
Multislice electron ptychography (MSEP) holds great promise for low-dose, depth-resolved structural characterization of materials, yet its reconstruction efficiency strongly depends on reliable probe initialization. This initialization relies on displacement analysis of single-pixel bright-field scanning transmission electron microscopy (BF-STEM) images. For crystalline specimens, however, the overlap between the bright-field disk and diffraction disks introduces additional contrast that weakens image similarity, thereby compromising the reliability of displacement measurements. Here, we propose a Fourier amplitude replacement (FAR) preprocessing strategy, in which the Fourier amplitude distribution of each single-pixel BF-STEM image is replaced with that of the axial BF-STEM image, thereby enhancing image similarity while preserving displacement-related Fourier phase information. Simulations and experiments demonstrate that FAR-assisted displacement analysis provides reliable probe initialization, leading to substantially higher quality MSEP reconstruction. This strategy offers a practical preprocessing approach for robust and efficient MSEP reconstruction of crystalline materials.
The nature of the intracellular acidic conditions (pH 5, mimicking endosomes/lysosomes tumor cells) compared to healthy tissues (pH 7.4) provides a unique opportunity for targeted cancer therapy using pH-responsive nanocarriers. However, the molecular mechanisms governing drug release under these conditions remain poorly understood, limiting rational design. This study employs a multiscale molecular dynamics approach; integrating all-atom molecular dynamics (AA-MD) and coarse-grained molecular dynamics (CG-MD), to investigate the pH-dependent release mechanism of temozolomide (TMZ), a first-line glioblastoma chemotherapeutic, from chitosan-Eudragit nanocarriers. Simulations were conducted under physiological (pH 7) and lysosomal-mimicking acidic (pH 5) conditions to elucidate how pH modulates drug-nanocarrier interactions.Our results reveal a clear pH-dependent switching mechanism. At neutral (pH 7), the system exhibits negative total interaction energy (dominated by van der Waals attractions ranging from -900 to -650 kJ/mol), extensive hydrogen bonding between TMZ and both polymer components, and a compact nanocarrier conformation as evidenced by a lower radius of gyration. These favorable interactions result in a five-fold larger drug-nanocarrier contact area at pH 7 compared to pH 5, promoting stable drug adsorption and retention. Conversely, under acidic conditions (pH 5), protonation of chitosan amine groups and Eudragit tertiary amine groups generates strong electrostatic repulsion (positive electrostatic energy of 800-1000 kJ/mol), disrupts hydrogen bond networks, and induces nanocarrier swelling, reflected in an increased radius of gyration and solvent-accessible surface area. This structural transformation reduces drug-nanocarrier affinity and facilitates TMZ release into the surrounding environment.The consistency between AA-MD (atomic-level interaction details) and CG-MD (larger-scale morphological changes) validates our findings across spatial and temporal scales. Critically, these results align with experimental observations from related chitosan-Eudragit systems while providing, for the first time, a molecular-level explanation for pH-triggered TMZ release. Our multiscale simulation framework offers predictive power to inform nanocarrier design parameters, such as chitosan degree of deacetylation and Eudragit composition, and provides a foundation for future optimization studies before costly in vitro and in vivo validation. These insights accelerate the development of effective, targeted therapeutic strategies for glioblastoma and other solid tumors characterized by an acidic microenvironment.
Atomic Force Microscopy (AFM) is a well-established and powerful technique used across fields ranging from materials science to biology and mechanobiology. It is also emerging as a valuable tool in clinical oncology, enabling the identification of nanomechanical biomarkers for cancer diagnosis. However, its effective integration into routine clinical practice remains unrealized. Cancer classification is typically based on the distribution of nanoscale mechanical properties, which may appear as single- or multi-peak profiles, yet the absence of a standardized theoretical framework for reproducible measurements remains a major obstacle.This paper proposes a robust analytical approach to address two primary sources of error in AFM-based cancer diagnosis: uncertainties in cantilever spring constant calibration and in the determination of the tip–sample contact point. Through a physics-based analysis, it is demonstrated that uncertainties in the spring constant (k) lead to a linear scaling of the calculated Young’s modulus (E), without altering the fundamental shape of the mechanical property distribution. Using weighted skew-normal distribution modeling, it is shown that diagnostic nanomechanical fingerprints remain identifiable even under significant calibration variability. Furthermore, a general rule for contact-point error propagation is established, showing that Young’s modulus estimation from contact stiffness reduces error sensitivity by at least a factor of three for spherical indenters and at least a factor of two for conical indenters, compared with force–indentation fitting using the classical Hertzian equations. Additionally, a threshold condition is defined using an elementary forced-oscillation model to identify the regime in which viscoelastic effects are minimized and the elastic approximation becomes valid. These results enhance the reliability of AFM as a diagnostic tool and provide a standardized methodology for monitoring treatment outcomes through quantitative mechanical signatures, supporting its future integration into clinical workflows.
Enzymatic diagnostics are based on naturally occurring enzymes, but they have limitations such as their inherent instability and high production costs, and they need to be stored under stringent conditions to maintain enzyme activity. Nanozymes are engineered nanomaterials with inbuilt enzyme-like catalytic activity that have become powerful and cost-effective alternatives that can withstand harsh environmental conditions. This systematic review critically reviews the recent status of nanozyme-based analytical platforms and summarizes the catalytic processes at atomic level of the most important classes of nanozymes such as metal oxides, noble metals, carbon-based materials and Metal-Organic Frameworks (MOFs). Beyond descriptive summaries, we critically evaluate how these materials have been translated to pharmaceutical quality control and clinical diagnostics, and what the actual impact and usefulness is of the quantification of the active ingredient and the identification of impurities in complex matrices. Moreover, this review highlights the development of nanozymes coupled with Point-of-Care (POC) devices such as lateral flow assays and microfluidic paper-based analytical devices (μPADs) for the instrument-free measurement of biomarker. Finally, we discuss the important translational challenges, primarily the substrate selectivity and regulatory compliance, and predict the rational development of highly efficient single-atom nanozymes.
Poly(ethylene glycol) (PEG) hydrogels have garnered significant attention in biomedical field due to their good biocompatibility, high water content, and tunable mechanical properties. However, their complex preparation and uncontrollable degradation still require improvement. In this study, photo-induced click chemistry was developed to prepare the medical PEG hydrogels. Linear PEG and tetra-arm-PEG were first functionalized to synthesize vinyl-terminated PEG (PEGDA) and thiol-terminated tetra-arm-PEG (tetra-PEG-SH); hydrogels (PEG−HGs) were subsequently formed between the two components via UV-induced thiol–ene click reaction. The effects of crosslinking density and solid content on the physicochemical properties of the PEG−HGs and lyophilized gels (DPEG−HGs) were investigated. As crosslinking density or solid content increased, the porosity of the DPEG−HGs decreased, while the water retention and compression resistance of the PEG−HGs significantly improved. In vitro drug-release tests indicated that the release rate was closely dependent on the degradation behavior of the hydrogel matrix. By adjusting the solid content of the PEG−HGs, the degradation rate and the duration of sustained drug release could be precisely regulated, achieving prolonged effective drug release over 6 − 10 weeks. Biological assessments revealed that PEG−HGs possessed > 75% cell survival ratio and < 5% hemolysis rates. The photo-induced click reaction enables simple processing and rapid gelation (< 30 s), yielding hydrogels with tunable mechanical properties, controllable degradation, and outstanding biocompatibility, which show great potential for biomedical applications and offer new insights for designing medical PEG hydrogels.
Polyethylene (PE) and isotactic polypropylene (iPP) are the most widely used semi-crystalline polyolefins, but their inherent immiscibility limits the bonding of dissimilar polyolefins and the upcycling of mixed waste streams. Conventional compatibilizers, such as olefin block copolymers (OBCs), bridge the PE/iPP interface through co-crystallization between their segments and the matrices, and therefore require processing close to the melting points (Tm) of the bulk polymers. In this study, we show that an ethylene-styrene-butadiene (ESB) random terpolymer adheres strongly to both high-density polyethylene (HDPE) and iPP through a mechanism that does not rely on co-crystallization. T-peel testing reveals that ESB establishes measurable adhesion from temperatures close to its own broad melting (approximately 60°C) to both matrices — that is, far below the matrix Tm — and that the peel strength rises further once the temperature exceeds the crystalline relaxation temperature of the matrix. Crucially, this low-temperature adhesion is observed even for the iPP/ESB system, in which co-crystallization between ESB and iPP is unexpected, demonstrating that co-crystallization is not a prerequisite for strong polyolefin compatibilization. Raman microscopy reveals that ESB and matrix chains interdiffuse over 5–10 μm across the interface. Cryo-TEM further confirms broad interdiffusion in both systems; an additional, system-dependent contribution from needle-like HDPE crystals growing into the ESB phase is observed only in the HDPE/ESB system. Together, these results establish amorphous-phase interdiffusion, likely driven by thermodynamic affinity rather than by segmental matching, as a sufficient mechanism for strong adhesion between dissimilar polyolefins, and provide a route to bond HDPE and iPP under thermal conditions that preserve the structural integrity of both matrices.
Growing environmental concerns and the increasing restrictions on toxic heavy–metal–based shielding materials have accelerated the development of sustainable lead-free materials. In this study Bi₂WO₆ nanosheets were incorporated into a P(VDF-TrFE) copolymer at different weight percentages (wt%) ranging from 1 to 10 wt% to fabricate P(VDF-TrFE)-Bi₂WO₆ flexible composite system with enhanced functional performance. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy were used to confirm the crystalline structure and vibrational modes of P(VDF-TrFE)-Bi₂WO₆ nanocomposite. The microstructure analysis confirms that the Bi₂WO₆ nanosheets were well dispersed in the P(VDF-TrFE) host. Introducing the Bi2WO6 sheet in P(VDF-TrFE) host strengthens the electrical response, reducing bulk plasmon energy from 24.72 to 21.5 eV and increasing mean excitation energy from 120.7 to 221 eV, increases stopping power, and slows down charge particles, with the smallest projected range PR to absorb protons and 3Li ions, notably at 10 wt% based on SRIM computations. Photon shielding performance was quantified for all polymer composites by simulating the linear attenuation coefficient (μ) over 0.015 MeV – 15 MeV energy range using Geant4 MC toolkit. The results are then compared with theoretical data computed through Phy-X/PSD software. Excellent agreement was achieved across the full energy range, with average percentage differences Δ%‾ of 0.209% to 0.566%, and a Goodness-of-Fit (χ2) of 5.81 × 10-5 to 4.35 × 10-2 confirming that the Geant4 setup reproduces the theoretical μ values with high fidelity.
As typical polymer lamellar crystals, two-dimensional (2D) platelets obtained from seeded growth of crystallizable block copolymers enable the regulation of their metastability through rational manipulation of crystallization pathways. Herein, the metastability of 2D platelets with crystalline poly(ε-caprolactone) (PCL) core is regulated by changing of crystallization temperatures, molecular weight of PCL and compositions of crystalline seeds. Experimental results have shown that colloidally stable PCL platelets would be created at a high crystallization temperature (4 °C), and these platelets are sufficiently stable to resist the structural change during aging process. In contrast, less stable PCL platelets are formed via seeded growth at a low crystallization temperature (-25 °C). Spontaneous fragmentation of less stable PCL platelet would occur when low-molecular-weight PCL composition is incorporated into PCL platelet particles, resulting in the formation of 2D hollow platelet structure. Moreover, it is further observed that the platelet fragmentation rate would accelerate when compositionally distinct crystalline seeds are used for seeded growth, which is due to the larger lattice mismatching degree between PCL and crystalline seeds. Mechanistic study has shown that the PCL platelets formed from low-molecular-weight PCL has a low melting temperature in ethanol solution, making them more susceptible to lamellar thickening via melt-recrystallization during aging/annealing process.
Coupling liquid–liquid phase separation (LLPS) with crystallization has emerged as an effective strategy for regulating polymer crystalline structures and elucidating crystallization mechanisms. In this work, we investigate the evaporative crystallization of poly(caprolactone) at water surface using three PCLs with different chain-end functionalities. By tailoring the chain ends and employing evaporative crystallization on water surfaces, the crystallization pathways were systematically controlled, enabling the formation of single-crystalline porous Janus films and two-dimensional (2D) Janus polymer single crystals. The observed structural evolution is attributed to the interplay between LLPS and crystallization during solvent evaporation. These results reveal a strong correlation between polymer chain conformation and crystalline morphology at liquid–liquid interfaces, providing new insights into interfacial polymer crystallization and the design of anisotropic polymeric structures.
Electroactive polymer (EAP) blends of relaxor-ferroelectric P(VDF-TrFE-CTFE) and ferroelectric P(VDF-TrFE) were investigated for enhanced electromechanical transduction. Blends containing 030 wt% copolymer were stencil-printed onto thin steel substrates for characterization in dielectric, mechanical, and structural properties, while unimorph cantilever actuators were produced for characterizing transduction. Copolymer addition increased the Young’s modulus and promoted ferroelectric ordering while reducing dielectric permittivity and dielectric loss in the EAPs. Maximum quasi-static actuation displacements improved from 8.1 mm at 50 V/μm in neat terpolymer samples to 9.2 mm at 48.3 V/μm in 10 wt% blends, that showed the highest overall improvements. At 20 V/μm, the maximum deflection and transducer efficiency respectively reached 2.1 mm and 0.0576%, corresponding to 94.4% and 357% improvements over the pure terpolymer. Under dynamic operation, the 10 wt% blends also produced the highest resonant displacement (2.30 mm at 6.7 V/μm), yielding a 53.7% improvement over the pure terpolymer. Higher copolymer contents (20 and 30 wt%) further increased in stiffness and unimorph efficiency but showed lower displacement due to reduced EAP film stress. These results demonstrate that polymer blending is an effective strategy to tune transduction performance in PVDF-based unimorph actuators, with further gains expected through optimization of blend composition and actuator design.
The conformation of polyelectrolyte (PE) brushes is highly sensitive to external conditions, particularly salt concentration and ion-specific effects. As salt concentration increases, PE brushes transition from an osmotic brush regime at low salt (H∝cs0) to a salted brush regime at high salt (H∝cs−1/3). However, deviations from this ideal scaling behavior are frequently observed in molecular simulations. In this work, we employ coarse-grained molecular dynamics simulations to systematically investigate how the sizes of counterions and co-ions affect the structural evolution and scaling behavior of PE brushes over a broad range of salt concentrations. Our results show that counterion size plays a dominant role in regulating ion penetration and coordination with PE monomers. At low salt concentrations, smaller counterions penetrate into the brush more easily, leading to enhanced local charge compensation and stronger brush collapse. At high salt concentrations, however, the brush height becomes largely insensitive to counterion size, while deviations from the classical scaling relation emerge. On the other hand, co-ion size mainly affects the system indirectly by modifying ion distributions and the local electrostatic environment. Smaller co-ions weaken local charge compensation and suppress brush collapse, with this effect becoming more pronounced at high salt concentrations. When the sizes of counterions and co-ions are reduced simultaneously, the system exhibits a coupled response. At low salt concentrations, the behavior remains counterion-dominated. At high salt concentrations, enhanced ion penetration and ion crowding modify the local ionic environment, leading to reentrant swelling and deviations from classical scaling relations. Collectively, this work provides a microscopic understanding of how ion size and salt concentration jointly govern the structural response of PE brushes and the emergence of non-classical scaling behavior in realistic solution environments.
Using self-seeding molecular dynamics simulations, we investigated how flexible chain transforms into stem in polyethylene crystal growth. Our simulations revealed a wedge-shaped growth front with a distinct interfacial layer of constant width. Outside this interfacial layer, chain segments retained flexible conformations indistinguishable from the amorphous. Upon entering the interfacial layer, van der Waals interactions from the crystal induced a conformational transition, leading to the formation of short initial stems. These initial stems then underwent linear followed by logarithmic thickening to form the long stems that consist of chain-folded lamellae. We confirmed that both thickening stages proceeded via a slip mechanism. The linear stage represented diffusion-controlled free slip, while the logarithmic regime corresponded to confined slip controlled by a barrier. The latter slip barrier was regulated by interfacial packing density, which is governed by amorphous conformation.
Ferroelectric nematic liquid crystals (FNLCs) represent a frontier in soft matter physics, offering unprecedented coupling between fluid order and electric polarization. However, achieving precise 3D control over their polar director fields remains a formidable challenge due to strong electrostatic interactions that typically favor uniform or twisted orientations. Here, we demonstrate the realization of a spontaneously stabilized "lying" polar helix—a configuration historically elusive in polar fluids—enabled by a bespoke chiral dopant. We uncover a distinct topological evolution driven by the competitive interplay between chirality and polar ordering: the system undergoes a symmetry-breaking transition from an apolar helix to a "lying" polar helix (FP1*), and ultimately to a "standing" polar helix (FP2*) mediated by topological soliton defects. Crucially, unlike conventional cholesteric fingerprints that require antagonistic confinement, this polar lying helix emerges as a thermodynamic ground state without external fields, offering a robust platform for self-assembled second-order nonlinear optical diffraction with microscale periodicity. We further demonstrate the arbitrary programmability of these superstructures via photopatterning and low-field switching. Our findings bridge the gap between soft-matter self-assembly and giant nonlinearity, establishing a paradigm for reconfigurable active topological photonics.
Surface defects, particularly longitudinal grooves, significantly limit the mechanical performance of carbon fibers (CFs). While these defects are often inherited from precursor fibers, quantitatively tracing their multi-scale evolution throughout the manufacturing process remains a critical challenge. Here, we present a novel, non-invasive analytical methodology combining atomic force microscopy (AFM) with two-dimensional Fast Fourier Transform (2D FFT) and inverse FFT (iFFT) reconstruction. This methodology resolves the complex surface topography of PAN-based fibers into three hierarchical levels, each attributable to the specific physical origins: microfibril stacking, fibril aggregation, and surface wrinkling. We successfully traced the evolution of these hierarchical groove structures through six key process stages, from coagulation to carbonization. This analysis revealed that groove evolution is dictated by a complex interplay of phase separation, axial drawing, and radial shrinkage, and the dominant mechanism varies at different stages. Most importantly, we established a direct correlation between the surface defects of the precursor fiber and the final mechanical performance of the carbon fiber. Our method precisely quantified how process-induced instability, marked by a dramatic deepening of grooves in early stages, directly compromises final fiber strength. Therefore, this work not only provides a powerful characterization technique but also serves as an invaluable tool for process monitoring and quality prediction, offering a new quantitative pathway to optimize the production of high-performance carbon fibers.
Thermoresponsive polymers have become substantial part of our modern life, for example in medical applications or as sensors. Thermoresponsive gelation is usually not accompanied by self-assembly processes, although a distinct supramolecular buildup could unlock even more potential such as increased mechanical stability. In this study, we present a novel thermoreversible material based on the protein fibrinogen, which self-assembles into a fibrous hydrogel at temperatures below 17.5°C and reversibly dissolves again above 35°C. This process can be repeated arbitrarily, making this process unique among fibrinogen-based materials. The key to this unique material is addition of Mg2+ ions to an aqueous fibrinogen solution, which renders the approach also highly attractive regarding its costs. In this study, the novel material is characterized by means of suited reaction conditions, gelation kinetics, and mechanical properties. Finally, hydrogels prepared from bovine and human fibrinogen are compared in detail. Remarkably, self-assembly of human protein is much faster and more robust compared to bovine protein.
Helical polyisocyanides have attracted considerable attention due to their stable helical conformations, yet incorporating acidic sulfonamide groups remains synthetically challenging. Herein, we report the first sulfonamide-functionalized helical polyisocyanide (Poly-PE-SA-PI). The key monomer was prepared via sulfonyl fluoride (SuFEx) click chemistry, followed by polymerization. The monomer exhibits unexpected stability due to hydrogen-bonded dimerization-a self-protection mechanism that challenges conventional notions of functional group incompatibility. The polymer adopts a stable one-handed helical conformation stabilized by aromatic pi-pi interactions rather than hydrogen bonding, as confirmed by TFA titration, and exhibits certain solvent polarity responsiveness: the helical structure becomes more compact, and the circular dichroism signal intensifies with increasing solvent polarity. Poly-PE-SA-PI displays highly selective fluoride ion (F-) recognition, with visible color change, UV-vis red-shift, and CD signal attenuation. Mechanism studies reveal that F-induces deprotonation of the sulfonamide groups, while the bulky tetrabutylammonium cation acts as a "cation-wedging" effector that cooperatively drives the conformational reorganization of the helix, enabling efficient and selective fluoride sensing. This work not only overcomes the synthetic challenges associated with polyisocyanides containing sulfonamide side chains but also provides a new class of materials toward helical polymers with precise ion-recognition capabilities. It holds promise for potential applications in chemical sensing, chiral separation, and smart optical devices.
To address the inherent trade-off between flame retardancy and mechanical properties in polypropylene (PP), a novel polyhedral oligomeric silsesquioxane-based flame retardant (POSS-PPA) was designed and synthesized in this work, and its synergistic effects with melamine polyphosphate (MPP) and piperazine pyrophosphate (PAPP) in PP composites were systematically investigated. Structural characterization confirmed the successful incorporation of phosphate groups onto a typical T8 caged POSS skeleton. Thermogravimetric analysis revealed that the char residue at 800 degrees C reached 63.9%, significantly higher than that of MPP (49.6%) and PAPP (31.0%). According to UL94 vertical burning tests and cone calorimetry measurements, the composite achieved a V-0 rating at a thickness of 1.6 mm. Notably, the composite containing four parts of the additive exhibited a peak heat release rate (PHRR) of 115.05 kW & centerdot;m-2, representing an 87.9% reduction compared to neat PP, while the total smoke production (TSP) was reduced to 190.63 m2 & centerdot;m-2, corresponding to a 78% decrease. Moreover, its notched impact strength reached 5.46 kJ & centerdot;m-2, marking a 22.4% enhancement relative to the composite without the novel flame retardant. This study presents a viable strategy for developing halogen-free flame-retardant PP composites with enhanced flame retardancy, smoke suppression, and mechanical strength.
